SUPPRESSION OF CYTOKINE RELEASE SYNDROME IN CHIMERIC ANTIGEN RECEPTOR CELL THERAPY

Abstract

Disclosed herein are methods of gene editing, or endogenous suppression, of cytokines/chemokines/transcription factors secreted from chimeric antigen receptor (CAR)-bearing immune effector cell such as CAR-T cells for the mitigation of cytokine release syndrome and/or CAR-T associated neuropathy. These methods involve insertion of the CAR into a locus of a cytokine gene, blocking its expression. Also disclosed herein are (CAR)-bearing immune effector cells with CARs inserted into a locus of a cytokine gene, and methods of treatment of diseases with immunotherapy with a reduced incidence of cytokine release syndrome and/or CAR-T associated neuropathy.

Description

[0001] This application claims the benefit of United States Provisional Application No. 62/679,597, filed Jun. 1, 2018, the disclosure of which is hereby incorporated by reference in its entirety.

SEQUENCE LISTING

[0002] The instant application contains a Sequence Listing which has been submitted electronically in ASCII format and is hereby incorporated by reference in its entirety. Said ASCII copy, created on Aug. 6, 2019, is named WGN0003-401-PC SL.txt and is 956,834 bytes in size.

[0003] CAR-T cells have emerged as a promising therapy for the treatment of hematological malignancies. Despite remarkable clinical efficacy against B cell malignancies, the success of CAR-T therapy has been limited by severe, life-threatening toxicities, observed in over 50% of patients. These toxicities have resulted in several deaths leading to early termination of clinical trial. Toxicities primarily manifest as cytokine release syndrome (CRS, also referred to as "cytokine storm") characterized by high elevations of cytokines including INFy, granulocyte-macrophage colony-stimulating factor, IL-10, and IL-6. These cytokine elevations result in a plethora of clinical symptoms including fever, hypotension, organ dysfunction, respiratory failure and coagulopathy. CRS can be fatal. Additionally, neurotoxicity often presents even after the initial symptoms of CRS have subsided. The pathogenesis of CRS and associated neurotoxicity is poorly understood and further understanding of the mechanism would be useful for the successful translation of CAR-T therapy. In the meanwhile, disrupting the pathogenesis of CRS by reducing the level of cytokine genes available for expression is one way to mitigate the condition.

[0004] Disclosed herein are methods of gene deletion and endogenous suppression, of cytokines/chemokines/transcription factors secreted from chimeric antigen receptor (CAR)-bearing immune effector cell, such as CAR-T cell, for the mitigation of cytokine release syndrome and/or CAR-T associated neuropathy. These gene deletion methods may include, but are not limited to, insertion of the CAR into a locus of a cytokine/chemokine/transcription factor gene, blocking its expression; gene editing with Transcription Activator-like Effector Nucleases (TALENs), Zinc Finger Nucleases (ZFNs), or CRISPR; expression of an scFv with an endoplasmic reticulum (ER) binding tether to bind the cytokine in the ER and prevent secretion; and transfection of small hairpin RNAs (shRNAs) or small interfering RNAs (siRNAs). Also disclosed herein are CAR-bearing immune effector cells modified with these described cytokine/chemokine/transcription factor gene deletion methods, and methods of treatment of diseases with immunotherapy with a reduced incidence of cytokine release syndrome (CRS) and/or CAR-T associated neuropathy (CAN).

BRIEF DESCRIPTION OF THE DRAWINGS

[0005] FIG. 1--Illustrates the concept of inserting a CAR into the gene for a cytokine in order to block its translation, thereby deleting it or reducing its level, thus preventing or reducing cytokine release syndrome and/or CAR-bearing immune effector cell associated neuropathy (CAR-T associated neuropathy).

[0006] FIG. 2--Shows a timeline for a method of treatment of hematologic malignancies using the CAR-T cells disclosed herein. Those of skill in the art will appreciate that some flexibility is possible in the time frames shown.

[0007] FIG. 3--Shows the AAV donor construct for insertion of CD34 into the GM-CSF locus.

[0008] FIG. 4--Shows the WC40 plasmid vector for use in inserting GFP into the CD3c locus.

[0009] FIG. 5--Shows the AAV donor construct for insertion of GFP into the CDR locus.

[0010] FIG. 6--Shows a CAR19-GM-CSF PEBL-trCD34 construct.

[0011] FIG. 7--Shows IL-6 expression in T cells, iDC cells, T cells+iDC, T cells+beads, and iDC+beads+T cells for GM-CSF knock-out, wild-type, and controls at 24 hours.

[0012] FIG. 8--Shows IL-6 expression in CAR19, iDC only, Act MQ only, MC only, RAMOS only, CAR19+iDC, CAR19+ActMQ, CAR19+MQ, CAR19+RAMOS, iDC+RAMOS+CAR-T, ActMQ+RAIVIOS+CAR-T, and MQ+RAMOS+CAR-T for CAR19 GM-CSF knock-out, CAR19, and controls at 24 hours.

[0013] FIG. 9--Shows IL-6 expression in T cells, iDC cells, T cells+iDC, T cells+beads, and iDC+beads+T cells for GM-CSF knock-out, wild-type, and controls at 48 hours.

[0014] FIG. 10--Shows IL-6 expression in CAR19, iDC only, Act MQ only, MC only, RAMOS only, CAR19+iDC, CAR19+ActMQ, CAR19+MQ, CAR19+RAMOS, iDC+RAMOS+CAR-T, ActMQ+RAIVIOS+CAR-T, and MQ+RAMOS+CAR-T for CAR19 GM-CSF knock-out, CAR19, and controls at 48 hours.

[0015] FIG. 11--Shows a set-up of an ELISA plate for detecting specific markers of CAR-T cells.

[0016] FIG. 12a and FIG. 12b--Shows the results for an ELISA assay detecting specific markers of the CAR-T cells. FIG. 12a shows the top half of the ELISA plate, and FIG. 12b shows the bottom half of the plate. In each of rows A-H, from top to bottom, the sub-rows indicate [450] test, [540] ref, Pathlength, 450, 540, Corrected [450], and Corrected [540].

DETAILED DESCRIPTION

[0017] Accordingly, disclosed herein as Embodiment 1 is a chimeric antigen receptor (CAR)-bearing immune effector cell that is deficient in a cytokine or in a chemokine or in a transcription factor that is involved in cytokine release syndrome.

[0018] The following disclosure will detail embodiments, alternatives, and uses of the cytokine-deficient cells, as well as the use of such cells in, for example, immunotherapy and adoptive cell transfer for the treatment of diseases. Accordingly, provided herein are the following additional embodiments.

[0019] Embodiment 2--The cell as recited in embodiment 1, wherein the cytokine or chemokine or transcription factor deficiency is effected by deletion or suppression of a gene encoding the cytokine or chemokine or transcription factor.

[0020] Embodiment 3--The cell as recited in any of embodiments 1 or 2, wherein the deletion or suppression is effected by inserting the CAR into a locus of the cytokine or chemokine or transcription factor gene.

[0021] Embodiment 4--The cell as recited in any of embodiments 1 to 3, wherein the CAR is part of a construct that also includes a selectable marker.

[0022] Embodiment 5--The cell as recited in any of embodiments 1 to 4, wherein the selectable marker comprises a green fluorescence (GFP) gene, a yellow fluorescent (YFP) gene, a truncated CD34 (tCD34) gene, or a truncated EGFR (tEGFR) gene.

[0023] Embodiment 6--The cell as recited in any of embodiments 1 to 5, wherein the cytokine or chemokine or transcription factor deficiency is effected by deletion or suppression of the cytokine or chemokine gene, by Transcription Activator-like Effector Nucleases (TALENs), Zinc Finger Nucleases (ZFNs), or Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) editing.

[0024] Embodiment 7--The cell as recited in any of embodiments 1 to 6, wherein deletion or suppression is effected using CRISPR.

[0025] Embodiment 8--The cell as recited in any of embodiments 1 to 7, wherein deletion or suppression is effected using Cas9-CRISPR.

[0026] Embodiment 9--The cell as recited in any of embodiments 1 to 8, wherein the Cas9 is delivered into the cell as mRNA or protein.

[0027] Embodiment 10--The cell as recited in any of embodiments 1 to 9, wherein the Cas9 is delivered into the cell as mRNA.

[0028] Embodiment 11--The cell as recited in any of embodiments 1 to 10, wherein the Cas9 is delivered into the cell as protein.

[0029] Embodiment 12--The cell as recited in any of embodiments 1 to 11, wherein a guide RNA (gRNA) targeting the gene to be deleted or suppressed is delivered contemporaneously with the Cas9.

[0030] Embodiment 13--The cell as recited in any of embodiments 1 to 12, wherein the delivery is by electroporation.

[0031] Embodiment 14--The cell as recited in any of embodiments 1 to 13, wherein the cytokine or chemokine or transcription factor deficiency is effected by suppression of the cytokine or chemokine or transcription factor gene transcript by transfection of one or more types of small interfering RNAs (siRNA).

[0032] Embodiment 15--The cell as recited in any of embodiments 1 to 14, wherein the cytokine or chemokine or transcription factor deficiency is effected by suppression of the cytokine or chemokine or transcription factor gene transcript by transduction of one or more types of short hairpin RNAs (shRNA).

[0033] Embodiment 16--A chimeric antigen receptor (CAR)-bearing immune effector cell expressing at least one CAR, wherein:

[0034] the at least one CAR is inserted into a locus of a cytokine or chemokine or transcription factor gene or transcription factor gene;

[0035] the cytokine or chemokine or transcription factor gene is deleted or suppressed by a method chosen from Transcription Activator-like Effector Nucleases (TALENs), Zinc Finger Nucleases (ZFNs), and Clustered Regularly Interspaces Short Palindromic Repeats (CRISPR) editing;

[0036] the cytokine or chemokine or transcription factor is suppressed by expression of an scFv with an endoplasmic reticulum (ER) binding tether to bind the cytokine or chemokine in the ER and prevent secretion;

[0037] the cytokine or chemokine or transcription factor gene transcript is suppressed by transfection of small interfering RNAs (siRNAs); or

[0038] the cytokine or chemokine or transcription factor gene transcript is suppressed by transduction of short hairpin RNAs (shRNAs).

[0039] Embodiment 17--The cell as recited in any of embodiments 1 to 16, wherein the cell is chosen from a chimeric antigen receptor T cell (CAR-T), a CAR-bearing iNKT cell (iNKT-CAR), and a CAR-bearing natural killer (NK) cell (NK-CAR), or a CAR-bearing macrophage.

[0040] Embodiment 18--The cell as recited in any of embodiments 1 to 17, wherein the cell is a CAR-T.

[0041] Embodiment 19--The cell as recited in any of embodiments 1 to 18, wherein the cell is a dual or tandem CAR-T.

[0042] Embodiment 20--The cell as recited in any of embodiments 1 to 17, wherein the cell is an iNKT-CAR.

[0043] Embodiment 21--The cell as recited in any of embodiments 1 to 20, wherein the cell is a dual or tandem iNKT-CAR.

[0044] Embodiment 22--The cell as recited in any of embodiments 1 to 17, wherein the cell is a CAR-macrophage.

[0045] Embodiment 23--The cell as recited in any of embodiments 1 to 22, wherein the cell is a dual or tandem CAR-macrophage.

[0046] Embodiment 24--The cell as recited in any of embodiments 1 to 23, wherein the cytokine or chemokine or transcription factor contributes to the development of cytokine release syndrome.

[0047] Embodiment 25--The cell as recited in any of embodiments 1 to 24, wherein the cytokine or chemokine or transcription factor is selected from among those recited in Table 10.

[0048] Embodiment 26--The cell as recited in any of embodiments 1 to 25, wherein the cytokine or chemokine or transcription factor is produced by T cells that activate or localize myeloid cells.

[0049] Embodiment 27--The cell as recited in any of embodiments 1 to 26, wherein the cytokine or chemokine or transcription factor is a T cell surface receptor gene that activates myeloid or CAR-T cells.

[0050] Embodiment 28--The cell as recited in any of embodiments 1 to 27, wherein the gene that is deleted or suppressed is a T cell surface receptor that is integrated into CAR-T cell signaling.

[0051] Embodiment 29--The cell as recited in any of embodiments 1 to 28, wherein the cytokine or chemokine or transcription factor drives T cell/CAR-T cell differentiation.

[0052] Embodiment 30--The cell as recited in any of embodiments 1 to 29, wherein the cytokine or chemokine is a transcription factor that drives T cell/CAR-T cell differentiation.

[0053] Embodiment 31--The cell as recited in any of embodiments 1 to 30, wherein the cytokine or chemokine or transcription factor is chosen from MCP1 (CCL2), MCP-2, GM-CSF, G-CSF, M-CSF, 11-4, and IFNy.

[0054] Embodiment 32--The cell as recited in any of embodiments 1 to 31, wherein the cytokine or chemokine or transcription factor is GM-CSF.

[0055] Embodiment 33--The cell as recited in any of embodiments 1 to 32, wherein the cell is a GM-CSF deficient CAR-T cell.

[0056] Embodiment 34--The cell as recited in any of embodiments 1 to 33, wherein the cell is a GM-CSF deficient iNKT-CAR cell.

[0057] Embodiment 35--The cell as recited in any of embodiments 1 to 34, wherein the immune effector cells to be used are harvested from a healthy donor.

[0058] Embodiment 36--The cell as recited in any of embodiments 1 to 35, wherein the donor is a human.

[0059] Embodiment 37--The cell as recited in any of embodiments 1 to 36, wherein the chimeric antigen receptor(s) specifically binds at least one antigen expressed on a malignant cell.

[0060] Embodiment 38--The cell as recited in any of embodiments 1 to 37, wherein the one or more antigens expressed on a malignant cell is chosen from BCMA, CS1, CD38, CD138, CD19, CD33, CD123, CD371, CD117, CD135, Tim-3, CD5, CD7, CD2, CD4, CD3, CD79A, CD79B, APRIL, CD56, and CD1a.

[0061] Embodiment 39--The cell as recited in any of embodiments 1 to 38, wherein the chimeric antigen receptor specifically binds at least one antigen expressed on a malignant T cell.

[0062] Embodiment 40--The cell as recited in any of embodiments 1 to 39, wherein the antigen is selected from CD2, CD3c, CD4, CD5, CD7, TCRA, and TCR.beta..

[0063] Embodiment 41--The cell as recited in any of embodiments 1 to 38, wherein the chimeric antigen receptor specifically binds at least one antigen expressed on a malignant B cell.

[0064] Embodiment 42--The cell as recited in any of embodiments 1 to 41, wherein the antigen is selected from CD19, CD20, CD21, CD22, CD23, CD24, CD25, CD27, CD38, and CD45.

[0065] Embodiment 43--The cell as recited in any of embodiments 1 to 42, wherein the antigen is selected from CD19 and CD20.

[0066] Embodiment 44--The cell as recited in any of embodiments 1 to 38, wherein the chimeric antigen receptor specifically binds at least one antigen expressed on a malignant mesothelial cell.

[0067] Embodiment 45--The cell as recited in any of embodiments 1 to 44, wherein the antigen is mesothelin.

[0068] Embodiment 46--The cell as recited in any of embodiments 1 to 38, wherein the chimeric antigen receptor specifically binds at least one antigen expressed on a malignant plasma cell.

[0069] Embodiment 47--The cell as recited in any of embodiments 1 to 46, wherein the antigen is selected from BCMA, CS1, CD38, and CD19.

[0070] Embodiment 48--The cell as recited in any of embodiments 1 to 47, wherein the chimeric antigen receptor expresses the extracellular portion of the APRIL protein, the ligand for BCMA and TACI, effectively co-targeting both BCMA and TACI.

[0071] Embodiment 49--The cell as recited in any of embodiments 1 to 48, wherein the CAR-T cell further comprises a suicide gene.

[0072] Embodiment 50--The cell as recited in any of embodiments 1 to 49, wherein endogenous T cell receptor mediated signaling is negligible in the cell.

[0073] Embodiment 51--The cell as recited in any of embodiments 1 to 50, wherein the cell does not induce alloreactivity or graft-versus-host disease.

[0074] Embodiment 52--The cell as recited in any of embodiments 1 to 51, wherein the cell does not induce fratricide.

[0075] Embodiment 53--A method of treatment of cancer in a patient, which has a reduced incidence of cytokine release syndrome and/or CAR-T associated neuropathy, comprising the administration of cells as recited in any of embodiments 1 to 52.

[0076] Embodiment 54--The method as recited in embodiment 53, wherein the cancer is a hematologic malignancy.

[0077] Embodiment 55--The method as recited in any of embodiments 53 to 54, wherein the hematologic malignancy is a T-cell malignancy.

[0078] Embodiment 56--The method as recited in any of embodiments 53 to 55, wherein the T cell malignancy is T-cell acute lymphoblastic leukemia (T-ALL).

[0079] Embodiment 57--The method as recited in any of embodiments 53 to 56, wherein the T cell malignancy is non-Hodgkin's lymphoma.

[0080] Embodiment 58--The method as recited in any of embodiments 53 to 57, wherein the hematologic malignancy is multiple myeloma.

[0081] Embodiment 59--The method as recited in any of embodiments 53 to 58, wherein the hematologic malignancy is AML.

[0082] Embodiment 60--The method as recited in any of embodiments 53 to 59, wherein the cancer is a solid tumor.

[0083] Embodiment 61--The method as recited any of embodiments 53 to 60, wherein the cancer is cervical cancer, pancreatic cancer, ovarian cancer, mesothelioma, and lung cancer.

[0084] Embodiment 62--A method of prevention or reduction of cytokine release syndrome or CAR-T associated neuropathy in a patient receiving chimeric antigen receptor T cell (CAR-T), CAR-bearing iNKT cell (iNKT-CAR), CAR-bearing natural killer (NK) cell (NK-CAR), or CAR-bearing macrophage (CAR-macrophage) immunotherapy, comprising the administration of cells as recited in any of embodiments 53 to 61 as the immunotherapy.

[0085] Embodiment 63--The method of any of embodiments 53 to 62, wherein the patient is being treated for cancer.

[0086] Embodiment 64--The method as recited in any of embodiments 53 to 63, wherein the cancer is a hematologic malignancy.

[0087] Embodiment 65--The method as recited in any of embodiments 53 to 64, wherein the hematologic malignancy is a T-cell malignancy.

[0088] Embodiment 66--The method as recited in any of embodiments 53 to 65, wherein the T cell malignancy is T-cell acute lymphoblastic leukemia (T-ALL).

[0089] Embodiment 67--The method as recited in any of embodiments 53 to 66, wherein the T cell malignancy is non-Hodgkin's lymphoma.

[0090] Embodiment 68--The method as recited in any of embodiments 53 to 67, wherein the hematologic malignancy is multiple myeloma.

[0091] Embodiment 69--The method as recited in any of embodiments 53 to 68, wherein the hematologic malignancy is AML.

[0092] Embodiment 70--The method as recited in any of embodiments 53 to 69, wherein the cancer is a solid tumor.

[0093] Embodiment 71--The method as recited in any of embodiments 53 to 70, wherein the cancer is cervical cancer, pancreatic cancer, ovarian cancer, mesothelioma, and lung cancer.

[0094] Embodiment 72--A method of blocking the expression of a cytokine gene or chemokine gene or transcription factor gene in a chimeric antigen receptor T cell (CAR-T), CAR-bearing iNKT cell (iNKT-CAR), CAR-bearing natural killer (NK) cell (NK-CAR), or CAR-bearing macrophage (CAR-macrophage) comprising the insertion of a CAR into a locus of the cytokine gene or chemokine gene or transcription factor gene.

[0095] Embodiment 73--The method of any of embodiments 53 to 72, wherein blocking the expression of the cytokine gene or chemokine gene or transcription factor gene does not reduce CAR-T cell-mediated killing.

[0096] Embodiment 74--A method of making a CAR-T (immune effector) cell that does not cause or contribute to CRS or CAR-T-associated neuropathy (CAN) comprising deleting or suppressing a cytokine or chemokine or transcription factor gene.

[0097] Embodiment 75--The method of any of embodiments 53 to 74, wherein deleting or suppressing the cytokine or chemokine or transcription factor gene does not reduce CAR-T cell-mediated killing.

[0098] Embodiment 76--The method as recited in any of embodiments 53 to 75, wherein the deletion or suppression is effected by inserting the CAR into a locus of the cytokine or chemokine or transcription factor gene.

[0099] Embodiment 77--The method as recited in any of embodiments 53 to 76, wherein the CAR is part of a construct that also includes a selectable marker.

[0100] Embodiment 78--The method as recited in any of embodiments 53 to 77, wherein the selectable marker comprises a green fluorescence (GFP) gene, a YFP gene, a tCD34 gene, or a tEGFR gene.

[0101] Embodiment 79--The method of any of embodiments 53 to 78, wherein the insertion of a CAR with a selectable marker into the cytokine or chemokine or transcription factor gene allows a single-step purification of TCR-negative cells.

[0102] Embodiment 80--The method of any of embodiments 53 to 79, wherein the insertion of a CAR with a selectable marker into the cytokine or chemokine or transcription factor gene allows a single step purification of CAR+ cytokine negative cells.

[0103] Embodiment 81--The method as recited in any of embodiments 53 to 80, wherein the deletion or suppression is effected using Transcription Activator-like Effector Nucleases (TALENs), Zinc Finger Nucleases (ZFNs), or Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) editing.

[0104] Embodiment 82--The method as recited in any of embodiments 53 to 81, wherein the deletion or suppression is effected using CRISPR.

[0105] Embodiment 83--The method as recited in any of embodiments 53 to 82, wherein the deletion or suppression is effected using Cas9-CRISPR.

[0106] Embodiment 84--The method as recited in any of embodiments 53 to 83, wherein the Cas9 is delivered into the cell as mRNA or protein.

[0107] Embodiment 85--The method as recited in any of embodiments 53 to 84, wherein the Cas9 is delivered into the cell as mRNA.

[0108] Embodiment 86--The method as recited in any of embodiments 53 to 85, wherein the Cas9 is delivered into the cell as protein.

[0109] Embodiment 87--The method as recited in any of embodiments 53 to 86, wherein a guide RNA (gRNA) targeting the gene to be deleted or suppressed is delivered contemporaneously with the Cas9.

[0110] Embodiment 88--The method as recited in any of embodiments 53 to 87, wherein the delivery is by electroporation.

[0111] Embodiment 89--The method as recited in any of embodiments 53 to 88, wherein the deletion or suppression is effected by suppression of the cytokine or chemokine or transcription factor gene transcript by transduction of one or more types of short hairpin RNAs (shRNA).

[0112] Embodiment 90--The method as recited in any of embodiments531 to 89, wherein the deletion or suppression is effected by transducing a construct encoding a protein expression blocker (PEBL).

[0113] Embodiment 91--The method of any of embodiments 53 to 90, wherein the construct encodes an antibody-derived single-chain variable fragment specific for the cytokine, chemokine or TF gene.

[0114] Embodiment 92--The method of any of embodiments 53 to 91, wherein deletion of the cytokine, chemokine, or transcription factor gene does not reduce CAR-T-mediated killing.

[0115] Embodiment 93--The method of any of embodiments 53 to 92, wherein the CAR to be inserted comprises a donor template.

[0116] Embodiment 94--The method of any of embodiments 53 to 93, wherein donor template comprises an adeno-associated virus (AAV), a single-stranded DNA, or a double-stranded DNA.

[0117] Disclosed herein is a chimeric antigen receptor (CAR)-bearing immune effector cell that is deficient in a cytokine.

[0118] In certain embodiments, the cytokine deficiency is effected by ablation of a cytokine gene or a chemokine gene, or a transcription factor gene.

[0119] In certain embodiments, the ablation is effected by inserting the CAR into a locus of the cytokine/chemokine/transcription factor gene.

[0120] In certain embodiments, the CAR is part of a construct that also includes a selectable marker.

[0121] In certain embodiments, the cytokine deficiency is effected by deletion or suppression of the cytokine/chemokine/transcription factor gene, by Transcription Activator-like Effector Nucleases (TALENs), Zinc Finger Nucleases (ZFNs), or Clustered Regularly Interspaces Short Palindromic Repeats (CRISPR) editing.

[0122] In certain embodiments, the cytokine deficiency is effected by suppression of the cytokine/chemokine/transcription factor gene transcript by transfection of small interfering RNAs (siRNAs).

[0123] Also disclosed herein is a chimeric antigen receptor (CAR)-bearing immune effector cell expressing at least one CAR, wherein:

[0124] the at least one CAR is inserted into a locus of a cytokine/chemokine/transcription factor gene;

[0125] the cytokine/chemokine/transcription factor gene is deleted or suppressed by a method chosen from Transcription Activator-like Effector Nucleases (TALENs), Zinc Finger Nucleases (ZFNs), and Clustered Regularly Interspaces Short Palindromic Repeats (CRISPR) editing;

[0126] the cytokine is suppressed by expression of an scFv with an endoplasmic reticulum (ER) binding tether to bind the cytokine in the ER and prevent secretion; or

[0127] the cytokine/chemokine/transcription factor gene transcript is suppressed by small interfering RNAs (siRNAs) transfection.

[0128] In certain embodiments, the cell is chosen from a chimeric antigen receptor T cell (CAR-T), a CAR-bearing iNKT cell (iNKT-CAR), and a CAR-bearing natural killer (NK) cell (NK-CAR).

[0129] In certain embodiments, the cell is a CAR-T.

[0130] In certain embodiments, the cell is a dual or tandem CAR-T.

[0131] In certain embodiments, the cell is an iNKT-CAR.

[0132] In certain embodiments, the cell is a dual or tandem iNKT-CAR.

[0133] In certain embodiments, the cytokine contributes to the development of cytokine release syndrome.

[0134] In certain embodiments, the cytokine is chosen from MCP1 (CCL2), MCP-2, GM-CSF, G-CSF, M-CSF, IL-4, and IFNy.

[0135] In certain embodiments, the cytokine is GM-CSF.

[0136] In certain embodiments, the cell is a GM-CSF deficient CAR-T cell.

[0137] In certain embodiments, the cell is a GM-CSF deficient iNKT-CAR cell.

[0138] In certain embodiments, the chimeric antigen receptor specifically binds at least one antigen expressed on a malignant T cell.

[0139] In certain embodiments, the antigen is selected from CD2, CDR, CD4, CD5, CD7, TCRA, and TCR.beta..

[0140] In certain embodiments, the chimeric antigen receptor specifically binds at least one antigen expressed on a malignant B cell.

[0141] In certain embodiments, the antigen is selected from CD19 and CD20.

[0142] In certain embodiments, the chimeric antigen receptor specifically binds at least one antigen expressed on a malignant mesothelial cell.

[0143] In certain embodiments, the antigen is mesothelin.

[0144] In certain embodiments, the chimeric antigen receptor specifically binds at least one antigen expressed on a malignant plasma cell.

[0145] In certain embodiments, the antigen is selected from BCMA, CS1, CD38, and CD19.

[0146] In certain embodiments, the chimeric antigen receptor expresses the extracellular portion of the APRIL protein, the ligand for BCMA and TACI, effectively co-targeting both BCMA and TACI.

[0147] In certain embodiments, the CAR-T cell further comprises a suicide gene.

[0148] In certain embodiments, endogenous T cell receptor mediated signaling is negligible in the cell.

[0149] In certain embodiments, the cell does not induce alloreactivity or graft-versus-host disease.

[0150] In certain embodiments, the cell does not induce fratricide.

[0151] Also disclosed herein is a method of treatment of cancer in a patient, which has a reduced incidence of cytokine release syndrome and/or CAR-T associated neuropathy, comprising the administration of chimeric antigen receptor (CAR)-bearing immune effector cells as disclosed herein.

[0152] In certain embodiments, the cancer is a hematologic malignancy.

[0153] In certain embodiments, the hematologic malignancy is a T-cell malignancy.

[0154] In certain embodiments, the T cell malignancy is T-cell acute lymphoblastic leukemia (T-ALL).

[0155] In certain embodiments, the T cell malignancy is non-Hodgkin's lymphoma.

[0156] In certain embodiments, the hematologic malignancy is multiple myeloma.

[0157] In certain embodiments, the cancer is a solid tumor.

[0158] In certain embodiments, the cancer is cervical cancer, pancreatic cancer, ovarian cancer, mesothelioma, and lung cancer.

[0159] Also disclosed herein is a method of prevention or reduction of cytokine release syndrome, CAR-T associated neuropathy in a patient receiving chimeric antigen receptor T cell (CAR-T), CAR-bearing iNKT cell (iNKT-CAR), or CAR-bearing natural killer (NK) cell (NK-CAR) immunotherapy, comprising the administration of chimeric antigen receptor (CAR)-bearing immune effector cells as disclosed herein as the immunotherapy.

[0160] Also disclosed herein is a method of blocking the expression of a cytokine/chemokine/transcription factor gene in a chimeric antigen receptor T cell (CAR-T), CAR-bearing iNKT cell (iNKT-CAR), or CAR-bearing natural killer (NK) cell (NK-CAR), comprising the insertion of a CAR into a locus of the cytokine/chemokine/transcription factor gene.

CAR-Bearing Immune Effector Cells

[0161] A chimeric antigen receptor (CAR), is a recombinant fusion protein comprising: 1) an extracellular ligand-binding domain, i.e., an antigen-recognition domain, 2) a transmembrane domain, and 3) a signaling transducing domain.

[0162] Methods for CAR design, delivery and expression, and the manufacturing of clinical-grade CAR-T cell populations are known in the art. See, for example, Lee et al., Clin. Cancer Res., 2012, 18(10): 2780-90. An engineered chimeric antigen receptor polynucleotide that encodes for a CAR comprises: a signal peptide, an antigen recognition domain, at least one co-stimulatory domain, and a signaling domain.

[0163] The antigen-specific extracellular domain of a chimeric antigen receptor recognizes and specifically binds an antigen, typically a surface-expressed antigen of a malignancy. An "antigen-specific extracellular domain" (or, equivalently, "antigen-binding domain") specifically binds an antigen when, for example, it binds the antigen with an affinity constant or affinity of interaction (KD) between about 0.1 pM to about 10 .mu.M, preferably about 0.1 pM to about 1 .mu.M, more preferably about 0.1 pM to about 100 nM. Methods for determining the affinity of interaction are known in the art. An antigen-specific extracellular domain suitable for use in a CAR of the present disclosure may be any antigen-binding polypeptide, a wide variety of which are known in the art. In some instances, the antigen-binding domain is a single chain Fv (scFv). Other antibody based recognition domains (cAb VHH (camelid antibody variable domains) and humanized versions thereof, lgNAR VH (shark antibody variable domains) and humanized versions thereof, sdAb VH (single domain antibody variable domains) and "camelized" antibody variable domains are suitable for use. In some instances, T-cell receptor (TCR) based recognition domains such as single chain TCR (scTv, single chain two-domain TCR containing V.alpha.V.beta.) are also suitable for use.

[0164] A chimeric antigen receptor of the present disclosure also comprises an "intracellular domain" that provides an intracellular signal to the CAR-bearing immune effector cell upon antigen binding to the antigen-specific extracellular domain. The intracellular signaling domain of a chimeric antigen receptor of the present disclosure is responsible for activation of at least one of the effector functions of the T cell in which the chimeric receptor is expressed. The term "effector function" refers to a specialized function of a differentiated cell, such as an iNKT cell. An effector function of an iNKT cell, for example, may be NK transactivation, T cell activation and differentiation, B cell activation, dendritic cell activation and cross-presentation activity, and macrophage activation. Thus, the term "intracellular domain" refers to the portion of a CAR that transduces the effector function signal upon binding of an antigen to the extracellular domain and directs the iNKT cell to perform a specialized function. Non-limiting examples of suitable intracellular domains include the zeta chain of the T-cell receptor or any of its homologs (e.g., eta, delta, gamma, or epsilon), MB 1 chain, 829, Fe Rill, Fe R1, and combinations of signaling molecules, such as CD3.zeta. and CD28, CD27, 4-1 BB, DAP-1 0, OX40, and combinations thereof, as well as other similar molecules and fragments. Intracellular signaling portions of other members of the families of activating proteins may be used, such as Fc.gamma.RIII and Fc.epsilon.RI. While usually the entire intracellular domain will be employed, in many cases it will not be necessary to use the entire intracellular polypeptide. To the extent that a truncated portion of the intracellular signaling domain may find use, such truncated portion may be used in place of the intact chain as long as it still transduces the effector function signal. The term intracellular domain is thus meant to include any truncated portion of the intracellular domain sufficient to transduce the effector function signal.

[0165] Typically, the antigen-specific extracellular domain is linked to the intracellular domain of the chimeric antigen receptor by a "transmembrane domain." A transmembrane domain traverses the cell membrane, anchors the CAR to the T cell surface, and connects the extracellular domain to the intracellular signaling domain, thus impacting expression of the CAR on the T cell surface. Chimeric antigen receptors may also further comprise one or more costimulatory domain and/or one or more spacer. A "costimulatory domain" is derived from the intracellular signaling domains of costimulatory proteins that enhance cytokine production, proliferation, cytotoxicity, and/or persistence in vivo. A "peptide hinge" connects the antigen-specific extracellular domain to the transmembrane domain. The transmembrane domain is fused to the costimulatory domain, optionally a costimulatory domain is fused to a second costimulatory domain, and the costimulatory domain is fused to a signaling domain, not limited to CD3.zeta.. For example, inclusion of a spacer domain between the antigen-specific extracellular domain and the transmembrane domain, and between multiple scFvs in the case of tandem CAR, may affect flexibility of the antigen-binding domain(s) and thereby CAR function. Suitable transmembrane domains, costimulatory domains, and spacers are known in the art.

[0166] Engineered CARs may be introduced into CAR-bearing immune effector cells using retroviruses, which efficiently and stably integrate a nucleic acid sequence encoding the chimeric antigen receptor into the target cell genome. Other methods known in the art include, but are not limited to, lentiviral transduction, transposon-based systems, direct RNA transfection, and CRISPR/Cas systems (e.g., type I, type II, or type Ill systems using a suitable Cas protein such Cas3, Cas4, Cas5, Cas5e (or CasD), Cash, Cas6e, Cas6f, Cas7, Cas8a1, Cas8a2, Cas8b, Cas8c, Cas9, Cas10, Cas1 Od, CasF, CasG, CasH, Csy1, Csy2, Csy3, Cse1 (or CasA), Cse2 (or CasB), Cse3 (or CasE), Cse4 (or CasC), Csc1, Csc2, Csa5, Csn2, Csm2, Csm3, Csm4, Csm5, Csm6, Cmr1, Cmr3, Cmr4, Cmr5, Cmr6, Csb1, Csb2, Csb3,Csx17, Csx14, Csx10, Csx16, CsaX, Csx3, Csz1, Csx15, Csf1, Csf2, Csf3, Csf4, and Cu1966, etc.). Zinc finger nucleases (ZFNs) and transcription activator-like effector nucleases (TALENs) may also be used. See, e.g., Shearer RF and Saunders DN, "Experimental design for stable genetic manipulation in mammalian cell lines: lentivirus and alternatives," Genes Cells 2015 January; 20(1):1-10.

[0167] Manipulation of PI3K signaling can be used to prevent altered CAR-T cell differentiation due to constitutive CAR self-signaling and foster long-lived memory T cell development. pharmacologic blockade of PI3K during CAR-T manufacture and ex vivo expansion can abrogate preferential effector T cell development and restore CAR-T effector/memory ratio to that observed in empty vector transduced T cells, which can improve in vivo T cell persistence and therapeutic activity. Inhibition of p110.delta. PI3K can enhance efficacy and memory in tumor-specific therapeutic CD8 T cells, while inhibition of p110.alpha. PI3K can increase cytokine production and antitumor response.

[0168] This is proposed to be because the presence of a CAR on a T cell's surface can alter its activation and differentiation, even in the absence of ligand. Constitutive self-signaling through CAR, related to both the scFv framework and the signaling domains, can lead to aberrant T cell behavior, including altered differentiation and decreased survival. This is significant as the effectiveness of CAR-T cells in patients is directly associated with their in vivo longevity. The presence of the CD28 costimulatory domain increased CAR-T cell exhaustion induced by persistent CAR self-signaling; the 4-1BB costimulatory domain had a lesser effect. Furthermore, CD3-zeta significantly enhances the constitutive activation of the PI3K, AKT, mTOR, and glycolysis pathways, and fostered formation of short-lived effector cells over central/stem memory cells. See, e.g., Zhang W. et al., "Modulation of PI3K signaling to improve CAR T cell function," Oncotarget, 2018 Nov. 9; 9(88): 35807-35808.

[0169] CAR Antigens. Suitable antigens to be genome-edited in the iNKT cells disclosed herein, and to be recognized by the CARs of iNKT-CARs disclosed herein, include antigens specific to hematologic malignancies. These can include T cell-specific antigens and/or antigens that are not specific to T cells. The antigen may be specifically bound by the chimeric antigen receptor of an iNKT-CARs cell, and the antigen for which the iNKT-CARs cell is deficient, is an antigen expressed on a malignant T cell, preferably an antigen that is overexpressed on malignant T cell (i.e., a T cell derived from a T-cell malignancy) in comparison to a nonmalignant T cell. Examples of such antigens include CD2, CD3.epsilon., CD4, CD5, CD7, TRAC, and TCR.beta..

[0170] T-cell malignancies comprise malignancies derived from T-cell precursors, mature T cells, or natural killer cells. Examples of T-cell malignancies include T-cell acute lymphoblastic leukemia/lymphoma (T-ALL), T-cell large granular lymphocyte (LGL) leukemia, human T-cell leukemia virus type 1-positive (HTLV-1 +) adult T-cell leukemia/lymphoma (ATL), T-cell prolymphocytic leukemia (T-PLL), and various peripheral T-cell lymphomas (PTCLs), including but not limited to angioimmunoblastic T-cell lymphoma (AITL), ALK-positive anaplastic large cell lymphoma, and ALK-negative anaplastic large cell lymphoma.

[0171] Suitable CAR antigens can also include antigens found on the surface of a multiple myeloma cell, i.e., a malignant plasma cell, such as BCMA, CS1, CD38, and CD19. Alternatively, the CAR may be designed to express the extracellular portion of the APRIL protein, the ligand for BCMA and TACI, effectively co-targeting both BCMA and TACI for the treatment of multiple myeloma.

[0172] Additional examples of suitable antigens to be genome-edited in the iNKT cells disclosed herein, and to be recognized by the CARs of iNKT-CARs disclosed herein, are given below in Tables 1-10. These include CD2, CD3.epsilon., CD4, CD5, CD7, TRAC, TCR.beta., BCMA, CS1, and CD38.

[0173] Fratricide Resistance. The CAR-T, iNKT, NK and other CAR-bearing immune effector cells encompassed by the present disclosure are optionally deficient in one or more antigens to which the chimeric antigen receptor specifically binds and are therefore fratricide-resistant. In some embodiments, the one or more antigens of the cell is modified such the chimeric antigen receptor no longer specifically binds the one or more modified antigens. For example, the epitope of the one or more antigens recognized by the chimeric antigen receptor may be modified by one or more amino acid changes (e.g., substitutions or deletions) or the epitope may be deleted from the antigen. In other embodiments, expression of the one or more antigens is reduced in the cell by at least 50%, at least 60%, at least 70%, at least 80%, at least 90% or more. Methods for decreasing the expression of a protein are known in the art and include, but are not limited to, modifying or replacing the promoter operably linked to the nucleic acid sequence encoding the protein. In still other embodiments, the cell is modified such that the one or more antigens is not expressed, e.g., by deletion or disruption of the gene encoding the one or more antigens. In each of the above embodiments, the CAR-bearing immune effector cell may be deficient in one or preferably all the antigens to which the chimeric antigen receptor specifically binds. Methods for genetically modifying a cell to be deficient in one or more antigens are well known in art, and non-limiting examples are provided above. In an exemplary embodiment, CRISPR/cas9 gene editing can be used to modify a cell to be deficient in one or more antigens. Zinc finger nucleases (ZFNs) and transcription activator-like effector nucleases (TALENs) may also be used. See, e.g., Shearer RF and Saunders DN, "Experimental design for stable genetic manipulation in mammalian cell lines: lentivirus and alternatives," Genes Cells 2015 January; 20(1):1-10.

[0174] Avoidance of Allogenicity. CAR-T, iNKT, NK and other CAR-bearing immune effector cells encompassed by the present disclosure may further be deficient in endogenous T cell receptor (TCR) signaling as a result of deleting a part of the T Cell Receptor (TCR)-CD3 complex. In various embodiments it may be desirable to eliminate or suppress endogenous TCR signaling in CAR-bearing immune effector cells disclosed herein. For example, decreasing or eliminating endogenous TCR signaling in CAR-T cells may prevent or reduce graft versus host disease (GvHD) when allogenic T cells are used to produce the CAR-T cells. Methods for eliminating or suppressing endogenous TCR signaling are known in the art and include, but are not limited to, deleting a part of the TCR-CD3 receptor complex, e.g., the TCR receptor alpha chain (TRAC), the TCR receptor beta chain (TRBC), CD3.epsilon. CD3.gamma. CD3.delta., and/or CD3.zeta.. Deleting a part of the TCR receptor complex may block TCR mediated signaling and may thus permit the safe use of allogeneic T cells as the source of CAR-T cells without inducing life-threatening GvHD.

[0175] Suicide Genes. Alternatively, or in addition, CAR-bearing immune effector cells encompassed by the present disclosure may further comprise one or more suicide genes. As used herein, "suicide gene" refers to a nucleic acid sequence introduced to a cell by standard methods known in the art that, when activated, results in the death of the cell. Suicide genes may facilitate effective tracking and elimination of the CAR-bearing immune effector cells in vivo if required. Facilitated killing by activating the suicide gene may occur by methods known in the art. Suitable suicide gene therapy systems known in the art include, but are not limited to, various the herpes simplex virus thymidine kinase (HSVtk)/ganciclovir (GCV) suicide gene therapy systems or inducible caspase 9 protein. In an exemplary embodiment, a suicide gene is a CD34/thymidine kinase chimeric suicide gene.

[0176] Components that may be included in a CAR as described herein are provided below in Tables 1 and 2.

TABLE-US-00001 TABLE 1 Amino acid sequences of different CAR components. SEQ ID Functional domains NO: Amino acid sequence CD8.alpha. signal peptide SEQ ID MALPVTALLLPLALLLHAARP NO: 1 CD8.alpha. hinge SEQ ID TTTPAPRPPTPAPTIASQPLSLRPEACRPAAGGA NO: 2 VHTRGLDFACD CD28 Transmembrane SEQ ID FWVLVVVGGVLACYSLLVTVAFIIFWV (T.sub.m) domain NO: 3 Surface glycoprotein CD8 SEQ ID MALPVTALLLPLALLLHAARPSQFRVSPLDRT alpha chain isoform 1 NO: 4 WNLGETVELKCQVLLSNPTSGCSWLFQPRGAA precursor ASPTFLLYLSQNKPKAAEGLDTQRFSGKRLGDT (NP_001139345.1) FVLTLSDFRRENEGYYFCSALSNSIMYFSHFVP VFLPAKPTTTPAPRPPTPAPTIASQPLSLRPEACR PAAGGAVHTRGLDFACDIYIWAPLAGTCGVLL LSLVITLYCNHRNRRRVCKCPRPVVKSGDKPSL SARYV 4-1BB costimulatory SEQ ID KRGRKKLLYIFKQPFMRPVQTTQEEDGCSCRFP domain NO: 5 EEEEGGCEL CD28 costimulatory SEQ ID RSKRSRLLHSDYMNMTPRRPGPTRKHYQPYAP domain NO: 6 PRDFAAYRS CD3 zeta (.zeta.) SEQ ID RVKFSRSADAPAYKQGQNQLYNELNLGRREEY NO: 7 DVLDKRRGRDPEMGGKPRRKNPQEGLYNELQ KDKMAEAYSEIGMKGERRRGKGHDGLYQGLS TATKDTYDALHMQALPPR P2A peptide SEQ ID GSGATNFSLLKQAGDVEENPGP NO: 8 (GGGGS).sub.4 linker SEQ ID GGGGSGGGGSGGGGSGGGGS NO: 9 hCD34 SEQ ID MPRGWTALCLLSLLPSGFMSLDNNGTATPELP NO: 10 TQGTFSNVSTNVSYQETTTPSTLGSTSLHPVSQ HGNEATTNITETTVKFTSTSVITSVYGNTNSSVQ SQTSVISTVFTTPANVSTPETTLKPSLSPGNVSD LSTTSTSLATSPTKPYTSSSPILSDIKAEIKCSGIR EVKLTQGICLEQNKTSSCAEFKKDRGEGLARV LCGEEQADADAGAQVCSLLLAQSEVRPQCLLL VLANRTEISSKLQLMKKHQSDLKKLGILDFTEQ DVASHQSYSQKTLIALVTSGALLAVLGITGYFL MNRRSWSPI Human-Herpes Simplex SEQ ID MPRGWTALCLLSLLPSGFMSLDNNGTATPELP Virus-1 (HSV)-thymidine NO: 11 TQGTFSNVSTNVSYQETTTPSTLGSTSLHPVSQ kinase (TK) HGNEATTNITETTVKFTSTSVITSVYGNTNSSVQ SQTSVISTVFTTPANVSTPETTLKPSLSPGNVSD LSTTSTSLATSPTKPYTSSSPILSDIKAEIKCSGIR EVKLTQGICLEQNKTSSCAEFKKDRGEGLARV LCGEEQADADAGAQVCSLLLAQSEVRPQCLLL VLANRTEISSKLQLMKKHQSDLKKLGILDFTEQ DVASHQSYSQKTLIALVTSGALLAVLGITGYFL MNRRSWSPTGEGGGGGDLGGVKLPHLFGKRL VEARMASYPCHQHASAFDQAARSRGHSNRRT ALRPRRQQEATEVRLEQKMPTLLRVYIDGPHG MGKTTTTQLLVALGSRDDIVYVPEPMTYWQV LGASETIANIYTTQHRLDQGEISAGDAAVVMTS AQITMGMPYAVTDAVLAPHVGGEAGSSHAPPP ALTLLLDRHPIAVMLCYPAARYLMGSMTPAV LAFVALIPPTLPGTNIVLGALPEDRHIDRLAKRQ RPGERLDLAMLAAIRRVYGLLANTVRYLQGGG SWWEDWGQLSGTAVPPQGAEPQSNAGPRPHIG DTLFTLFRAPELLAPNGDLYNVFAWALDVLAK RLRPMHVFILDYDQSPAGCRDALLQLTSGMVQ THVTTPGSIPTICDLARTFAREMGEAN

TABLE-US-00002 TABLE 2 Amino acid sequences of the variable heavy (V.sub.H) and variable light (V.sub.L) chains of the scFvs. SEQ ID ScFv sequences NO: Amino acid sequence CD2 heavy chain variable SEQ ID EVKLEESGAELVKPGASVKLSCRTSGFN1KDTI region (35.1 ATCC .RTM. HB- NO: 12 HWVKQRPEQGLKWIGRIDPANGNTKYDPKFQ 222.sup.TM) DKATVTADTSSNTAYLQLSSLTSEDTAVYYCV TYAYDGNWYFDVWGAGTAVTVSS CD2 light chain variable SEQ ID DIKNITQSPSSMYVSLGERVTITCKASQDINSFL region (35.1 ATCC .RTM. HB- NO: 13 SWFQQKPGKSPKTLIYRANRLVDGVPSRFSGS 222.sup.TM) GSGQDYSLTISSLEYEDMEIYYCLQYDEFPYTF GGGTKLEMKR CD2 heavy chain variable SEQ ID EVQLEESGAELVRPGTSVKLSCKASGYTFTSY region (OKT 11 NO: 14 WMHWIKQRPEQGLEWIGRIDPYDSETHYNEK ATCC .RTM. CRL-8027.sup.TM) FKDKAILSVDKSSSTAYIQLSSLTSDDSAVYYC SRRDAKYDGYALDYWGQGTSVTVSS CD2 light chain variable SEQ ID DIVMTQAAPSVPVTPGESVSISCRSSKTLLHSN region (OKT 11 NO: 15 GNTYLYWFLQRPGQSPQVLIYRMSNLASGVP ATCC .RTM. CRL-8027.sup.TM) NRFSGSGSETTFTLRISRVEAEDVGIYYCMQHL EYPYTFGGGTKLEIER CD3 heavy chain variable SEQ ID GSQVQLQQSGAELARPGASVKMSCKASGYTF region (OKT 3) NO: 16 TRYTMHWVKQRPGQGLEWIGYINPSRGYTNY NQKFKDKATLTTDKSSSTAYMQLSSLTSEDSA VYYCARYYDDHYCLDYWGQGTTLTVSS CD3 light chain variable SEQ ID QIVLTQSPAIIVISASPGEKVTMTCSASSSVSYM region (OKT 3) NO: 17 NWYQQKSGTSPKRWIYDTSKLASGVPAHFRG SGSGTSYSLTISGMEAEDAATYYCQQWSSNPF TFGSGTKLEINR CD3 heavy chain variable SEQ ID EVQLVESGGGLVQPGGSLRLSCAASGYSFTGY region (UCHT1) NO: 18 TMNWVRQAPGKCLEWVALINPYKGVSTYNQ KFKDRFTISVDKSKNTAYLQMNSLRAEDTAV YYCARSGYYGDSDWYFDVWGQGTLVTVSS CD3 heavy chain variable SEQ ID DIQMTQSPSSLSASVGDRVTITCRASQDIRNYL region (UCHT1) NO: 19 NWYQQKPGKAPKLLIYYTSRLESGVPSRFSGS GSGTDYTLTISSLQPEDFATYYCQQGNTLPWT FGCGTKVEIK CD7 heavy chain variable SEQ ID EVQLVESGGGLVKPGGSLKLSCAASGLTFSSY region NO: 20 AMSWVRQTPEKRLEWVASISSGGFTYYPDSV KGRFTISRDNARNILYLQMSSLRSEDTAMYYC ARDEVRGYLDVWGAGTTVTVS CD7 light chain variable SEQ ID DIQMTQTTSSLSASLGDRVTISCSASQGISNYL region NO: 21 NWYQQKPDGTVKLLIYYTSSLHSGVPSRFSGS GSGTDYSLTISNLEPEDIATYYCQQYSKLPYTF GGGTKLEIKR FTL3 heavy chain SEQ ID EVQLVQSGAEVKKPGASVKVSCKASGYTFTS variable region (EB10) NO: 22 YYMHWVRQAPGQGLEWMGIINPSGGSTSYAQ KFQGRVTMTRDTSTSTVYMELSSLRSEDTAVY YCARGVGAHDAFDIWGQGTTVTVSS FTL3 light chain variable SEQ ID DVVMTQSPLSLPVTPGEPASISCRSSQSLLHSN region (EB10) NO: 23 GNNYLDWYLQKPGQSPQLLIYLGSNRASGVP DRFSGSGSDTDFTLQISRVEAEDVGVYYCMQG THPAISFGQGTRLEIK FTL3 heavy chain SEQ ID EVQLVQSGAEVKKPGSSVKVSCKASGGTFSSY variable region (NC7) NO: 24 AISWVRQAPGQGLEWMGGIIPIFGTANYAQKF QGRVTITADKSTSTAYMELSSLRSEDTAVYYC ATFALFGFREQAFDIWGQGTTVTVSS FTL3 light chain variable SEQ ID DIQMTQSPSSLSASVGDRVTITCRASQSISSYLN region (NC7) NO: 25 WYQQKPGKAPKLLIYAASSLQSGVPSRFSGSG SGTDFTLTISSLQPEDLATYYCQQSYSTPFTFGP GTKVDIK FTL3 heavy chain SEQ ID EVQLVQSGAEVKKPGASVKVSCKASGYTFTS variable region (D3-D4) NO: 26 YYMHWARQAPGQGLEWMGIINPSGGSTSYAQ KFQGRVTMTRDTSTSTVYMELSSLRSEDTAVY YCARVVAAAVADYWGQGTLVTVSS FTL3 light chain variable SEQ ID DVVMTQSPLSLPVTPGEPASISCRSSQSLLHSN region (D3-D4) NO: 27 GYNYLDWYLQKPGQSPQLLIYLGSNRASGVP DRFSGSGSGTDFTLKISRVEAEDVGVYYCMQS LQTPFTFGPGTKVDIK CS1 heavy chain variable SEQ ID QVQLQQPGAELVRPGASVKLSCKASGYSFTTY region NO: 28 WMNWVKQRPGQGLEWIGMIHPSDSETRL NQKFKDKATLTVDKSSSTAYMQLSSPTSEDSA VYYCARSTMIATRAMDYWGQGTSVTVSS CS1 light chain variable SEQ ID DIVMTQSQKSMSTSVGDRVSITCKASQDVITG region NO: 29 VAWYQQKPGQSPKLLIYSASYRYTGVPD RFTGSGSGTDFTFTISNVQAEDLAVYYCQQHY STPLTFGAGTKLELK CD33 heavy chain SEQ ID QVQLQQPGAEVVKPGASVKMSCKASGYTFTS variable region NO: 30 YYIHWIKQTPGQGLEWVGVIYPGNDDISYNQK FQGKATLTADKSSTTAYMQLSSLTSEDSAVYY CAREVRLRYFDVWGQGTTVTVSSSG CD33 light chain variable SEQ ID GSEIVLTQSPGSLAVSPGERVTMSCKSSQSVFF region NO: 31 SSSQKNYLAWYQQIPGQSPRLLIYWASTRESG VPDRFTGSGSGTDFTLTISSVQPEDLAIYYCHQ YLSSRTFGQGTKLEIKR

Mono CAR-T Cells

[0177] In certain embodiments, the disclosure provides an engineered T cell comprising a single CAR, that specifically binds an antigen or cell surface protein, wherein the T cell is optionally deficient in that antigen or cell surface protein (e.g., CD7CART.DELTA.CD7 cell). In non-limiting examples, the deficiency in the antigen or cell surface protein resulted from (a) modification of antigen or cell surface protein expressed by the T cell such that the chimeric antigen receptors no longer specifically binds the modified antigen or cell surface protein (e.g., the epitope of the one or more antigens recognized by the chimeric antigen receptor may be modified by one or more amino acid changes (e.g., substitutions or deletions) or the epitope may be deleted from the antigen), (b) modification of the T cell such that expression of antigen or cell surface protein is reduced in the T cell by at least 50%, at least 60%, at least 70%, at least 80%, at least 90% or more, or (c) modification of the T cell such that antigen or cell surface protein is not expressed (e.g., by deletion or disruption of the gene encoding antigen or cell surface protein). In each of the above embodiments, the CAR-T cell may be deficient in one or preferably all the antigens or cell surface proteins to which the chimeric antigen receptor specifically binds. The methods to genetically modify a T cell to be deficient in one or more antigens or cell surface proteins are well known in art and non-limiting examples are provided herein. In embodiments described below, the CRISPR-Cas9 system is used to modify a T cell to be deficient in one or more antigens. Any of these may be accomplished by the methods disclosed herein. In further embodiments, the T cell comprises a suicide gene.

[0178] For example, the CAR for a CD7 specific CAR-T cell may be generated by cloning a commercially synthesized anti-CD7 single chain variable fragment (scFv) into a 3rd generation CAR backbone with CD28 and/or 4-1BB internal signaling domains. An extracellular hCD34 domain may be added after a P2A peptide to enable both detection of CAR following viral transduction and purification using anti-hCD34 magnetic beads. A similar method may be followed for making CARs specific for other malignant T cell antigens.

[0179] CAR-T cells encompassed by the present disclosure may further be deficient in endogenous T cell receptor (TCR) signaling as a result of deleting a part of the T Cell Receptor (TCR)-CD3 complex. In various embodiments it may be desirable to eliminate or suppress endogenous TCR signaling in CAR-T cells disclosed herein. For example, decreasing or eliminating endogenous TCR signaling in CAR-T cells may prevent or reduce graft versus host disease (GvHD) when allogenic T cells are used to produce the CAR-T cells. Methods for eliminating or suppressing endogenous TCR signaling are known in the art and include, but are not limited to, deleting a part of the TCR-CD3 receptor complex, e.g., the TCR receptor alpha chain (TRAC), the TCR receptor beta chain (TCR.beta.) or subtypes thereof, TCR.delta., TCR.gamma., CD3.epsilon., CD3.gamma., and/or CD3.delta.. Deleting a part of the TCR receptor complex may block TCR mediated signaling and may thus permit the safe use of allogeneic T cells as the source of CAR-T cells without inducing life-threatening GvHD.

[0180] In addition, the CAR-T cells encompassed by the present disclosure may further comprise one or more suicide genes as described herein.

[0181] In a similar manner, other mono-CAR-T cells may be constructed and are given below in Table 3.

TABLE-US-00003 TABLE 3 Mono CARs and CAR-Ts Antigen Antigen Target of Deletion/ CAR-T Suppression Example cells cells M1 APRIL -- M2 APRIL APRIL M3 APRIL APRIL + TRAC M4 APRIL APRIL + CD3.epsilon. M5 APRIL CD3.epsilon. M6 BCMA -- M7 CD117 -- M8 CD117 CD117 M9 CD123 -- M10 CD123 CD123 M11 CD135 -- M12 CD135 CD135 M13 CD138 -- M14 CD19 -- M15 CD1a -- M16 CD1a CD3.epsilon. M17 CD1a TRAC M18 CD1a CD1a + TRAC M19 CD1a CD1a + CD3.epsilon. M20 CD2 -- M21 CD2 CD2 M22 CD2 CD2 + TRAC M23 CD2 CD2 + CD3.epsilon. M24 CD20 M25 CD21 M26 CD22 M27 CD23 M28 CD3 -- M29 CD3 CD3.epsilon. M30 CD3 CD3.epsilon. + TRAC M31 CD33 -- M32 CD33 CD33 M33 CD371 -- M34 CD371 CD371 M35 CD38 -- M36 CD38 CD38 M37 CD4 -- M38 CD4 CD4 M39 CD4 CD4 + TRAC M40 CD4 CD4 + CD3.epsilon. M41 CD5 -- M42 CD5 CD5 M43 CD5 CD5 + TRAC M44 CD5 CD5 + CD3.epsilon. M45 CD56 -- M46 CD56 CD56 M47 CD56 CD56 + TRAC M48 CD56 CD56 + CD3.epsilon. M49 CD56 CD3.epsilon. M50 CD56 TRAC M51 CD7 -- M52 CD7 CD7 M53 CD7 CD7 + TRAC M54 CD7 CD7 + CD3.epsilon. M55 CD79A -- M56 CD79B -- M57 CS1 -- M58 CS1 CS1 M59 Tim-3 -- M60 Tim-3 Tim-3 M61 Tim-3 Tim-3 + TRAC M62 Tim-3 TRAC M63 Tim-3 CD3.epsilon. M64 Tim-3 Tim-3 + CD3.epsilon.

[0182] Disclosed are embodiments of CAR amino acid sequences that can be expressed on the surface of a genome-edited CAR-T cell derived from a cytotoxic T cell, a memory T cell, or a gamma delta (.gamma..delta.) T cell.

TABLE-US-00004 TABLE 4 Amino Acid Sequences of Mono Chimeric Antigen Receptors (CARs). Mono CAR Constructs SEQ ID NO: Amino acid sequence CD7-CAR-4- SEQ ID MALPVTALLLPLALLLHAARPDIQMTQTTSSLSASLGDRVT 1BB_CD34 NO: 32 ISCSASQGISNYLNWYQQKPDGTVKLLIYYTSSLHSGVPSRF SGSGSGTDYSLTISNLEPEDIATYYCQQYSKLPYTFGGGTKL EIKRGGGGSGGGGSGGGGSGGGGSEVQLVESGGGLVKPG GSLKLSCAASGLTFSSYAMSWVRQTPEKRLEWVASISSGGF TYYPDSVKGRFTISRDNARNILYLQMSSLRSEDTAMYYCA RDEVRGYLDVWGAGTTVTVSPRASTTTPAPRPPTPAPTIAS QPLSLRPEACRPAAGGAVHTRGLDFACDFWVLVVVGGVL ACYSLLVTVAFIIFWVKRGRKKLLYIFKQPFMRPVQTTQEE DGCSCRFPEEEEGGCELRVKFSRSADAPAYKQGQNQLYNE LNLGRREEYDVLDKRRGRDPEMGGKPRRKNPQEGLYNEL QKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTY DALHMQALPPRRTDGSGATNFSLLKQAGDVEENPGPVSEA MPRGWTALCLLSLLPSGFMSLDNNGTATPELPTQGTFSNVS TNVSYQETTTPSTLGSTSLHPVSQHGNEATTNITETTVKFTS TSVITSVYGNTNSSVQSQTSVISTVFTTPANVSTPETTLKPSL SPGNVSDLSTTSTSLATSPTKPYTSSSPILSDIKAEIKCSGIRE VKLTQGICLEQNKTSSCAEFKKDRGEGLARVLCGEEQADA DAGAQVCSLLLAQSEVRPQCLLLVLANRTEISSKLQLMKK HQSDLKKLGILDFTEQDVASHQSYSQKTLIALVTSGALLAV LGITGYFLMNRRSWSPI CD7-CAR-4- SEQ ID MALPVTALLLPLALLLHAARPDIQMTQTTSSLSASLGDRVT 1BB_CD34_TK NO: 33 ISCSASQGISNYLNWYQQKPDGTVKLLIYYTSSLHSGVPSRF SGSGSGTDYSLTISNLEPEDIATYYCQQYSKLPYTFGGGTKL EIKRGGGGSGGGGSGGGGSGGGGSEVQLVESGGGLVKPG GSLKLSCAASGLTFSSYAMSWVRQTPEKRLEWVASISSGGF TYYPDSVKGRFTISRDNARNILYLQMSSLRSEDTAMYYCA RDEVRGYLDVWGAGTTVTVSPRASTTTPAPRPPTPAPTIAS QPLSLRPEACRPAAGGAVHTRGLDFACDFWVLVVVGGVL ACYSLLVTVAFIIFWVKRGRKKLLYIFKQPFMRPVQTTQEE DGCSCRFPEEEEGGCELRVKFSRSADAPAYKQGQNQLYNE LNLGRREEYDVLDKRRGRDPEMGGKPRRKNPQEGLYNEL QKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTY DALHMQALPPRRTDGSGATNFSLLKQAGDVEENPGPVSEA MPRGWTALCLLSLLPSGFMSLDNNGTATPELPTQGTFSNVS TNVSYQETTTPSTLGSTSLHPVSQHGNEATTNITETTVKFTS TSVITSVYGNTNSSVQSQTSVISTVFTTPANVSTPETTLKPSL SPGNVSDLSTTSTSLATSPTKPYTSSSPILSDIKAEIKCSGIRE VKLTQGICLEQNKTSSCAEFKKDRGEGLARVLCGEEQADA DAGAQVCSLLLAQSEVRPQCLLLVLANRTEISSKLQLMKK HQSDLKKLGILDFTEQDVASHQSYSQKTLIALVTSGALLAV LGITGYFLMNRRSWSPTGEGGGGGDLGGVKLPHLFGKRLV EARMASYPCHQHASAFDQAARSRGHSNRRTALRPRRQQE ATEVRLEQKMPTLLRVYIDGPHGMGKTTTTQLLVALGSRD DIVYVPEPMTYWQVLGASETIANIYTTQHRLDQGEISAGDA AVVMTSAQITMGMPYAVTDAVLAPHVGGEAGSSHAPPPA LTLLLDRHPIAVMLCYPAARYLMGSMTPQAVLAFVALIPPT LPGTNIVLGALPEDRHIDRLAKRQRPGERLDLAMLAAIRRV YGLLANTVRYLQGGGSWWEDWGQLSGTAVPPQGAEPQS NAGPRPHIGDTLFTLFRAPELLAPNGDLYNVFAWALDVLA KRLRPMHVFILDYDQSPAGCRDALLQLTSGMVQTHVTTPG SIPTICDLARTFAREMGEAN CD7-CAR- SEQ ID MALPVTALLLPLALLLHAARPDIQMTQTTSSLSASLGDRVT CD28_CD34 NO: 34 ISCSASQGISNYLNWYQQKPDGTVKLLIYYTSSLHSGVPSRF SGSGSGTDYSLTISNLEPEDIATYYCQQYSKLPYTFGGGTKL EIKRGGGGSGGGGSGGGGSGGGGSEVQLVESGGGLVKPG GSLKLSCAASGLTFSSYAMSWVRQTPEKRLEWVASISSGGF TYYPDSVKGRFTISRDNARNILYLQMSSLRSEDTAMYYCA RDEVRGYLDVWGAGTTVTVSPRASTTTPAPRPPTPAPTIAS QPLSLRPEACRPAAGGAVHTRGLDFACDFWVLVVVGGVL ACYSLLVTVAFIIFWVRSKRSRLLHSDYMNMTPRRPGPTRK HYQPYAPPRDFAAYRSRVKFSRSADAPAYKQGQNQLYNE LNLGRREEYDVLDKRRGRDPEMGGKPRRKNPQEGLYNEL QKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTY DALHMQALPPRRTDGSGATNFSLLKQAGDVEENPGPVSEA MPRGWTALCLLSLLPSGFMSLDNNGTATPELPTQGTFSNVS TNVSYQETTTPSTLGSTSLHPVSQHGNEATTNITETTVKFTS TSVITSVYGNTNSSVQSQTSVISTVFTTPANVSTPETTLKPSL SPGNVSDLSTTSTSLATSPTKPYTSSSPILSDIKAEIKCSGIRE VKLTQGICLEQNKTSSCAEFKKDRGEGLARVLCGEEQADA DAGAQVCSLLLAQSEVRPQCLLLVLANRTEISSKLQLMKK HQSDLKKLGILDFTEQDVASHQSYSQKTLIALVTSGALLAV LGITGYFLMNRRSWSPI CD7-CAR- SEQ ID MALPVTALLLPLALLLHAARPDIQMTQTTSSLSASLGDRVT CD28_CD34_TK NO: 35 ISCSASQGISNYLNWYQQKPDGTVKLLIYYTSSLHSGVPSRF SGSGSGTDYSLTISNLEPEDIATYYCQQYSKLPYTFGGGTKL EIKRGGGGSGGGGSGGGGSGGGGSEVQLVESGGGLVKPG GSLKLSCAASGLTFSSYAMSWVRQTPEKRLEWVASISSGGF TYYPDSVKGRFTISRDNARNILYLQMSSLRSEDTAMYYCA RDEVRGYLDVWGAGTTVTVSPRASTTTPAPRPPTPAPTIAS QPLSLRPEACRPAAGGAVHTRGLDFACDFWVLVVVGGVL ACYSLLVTVAFIIFWVRSKRSRLLHSDYMNMTPRRPGPTRK HYQPYAPPRDFAAYRSRVKFSRSADAPAYKQGQNQLYNE LNLGRREEYDVLDKRRGRDPEMGGKPRRKNPQEGLYNEL QKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTY DALHMQALPPRRTDGSGATNFSLLKQAGDVEENPGPVSEA MPRGWTALCLLSLLPSGFMSLDNNGTATPELPTQGTFSNVS TNVSYQETTTPSTLGSTSLHPVSQHGNEATTNITETTVKFTS TSVITSVYGNTNSSVQSQTSVISTVFTTPANVSTPETTLKPSL SPGNVSDLSTTSTSLATSPTKPYTSSSPILSDIKAEIKCSGIRE VKLTQGICLEQNKTSSCAEFKKDRGEGLARVLCGEEQADA DAGAQVCSLLLAQSEVRPQCLLLVLANRTEISSKLQLMKK HQSDLKKLGILDFTEQDVASHQSYSQKTLIALVTSGALLAV LGITGYFLMNRRSWSPTGEGGGGGDLGGVKLPHLFGKRLV EARMASYPCHQHASAFDQAARSRGHSNRRTALRPRRQQE ATEVRLEQKMPTLLRVYIDGPHGMGKTTTTQLLVALGSRD DIVYVPEPMTYWQVLGASETIANIYTTQHRLDQGEISAGDA AVVMTSAQITMGMPYAVTDAVLAPHVGGEAGSSHAPPPA LTLLLDRHPIAVMLCYPAARYLMGSMTPQAVLAFVALIPPT LPGTNIVLGALPEDRHIDRLAKRQRPGERLDLAMLAAIRRV YGLLANTVRYLQGGGSWWEDWGQLSGTAVPPQGAEPQS NAGPRPHIGDTLFTLFRAPELLAPNGDLYNVFAWALDVLA KRLRPMHVFILDYDQSPAGCRDALLQLTSGMVQTHVTTPG SIPTICDLARTFAREMGEAN CD79B-CAR- SEQ ID MALPVTALLLPLALLLHAARPGSDIQLTQSPSSLSASVGDR CD28_CD34 NO: 36 VTITCKASQSVDYEGDSFLNWYQQKPGKAPKLLIYAASNL ESGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQSNEDPL TFGQGTKVEIKRGGGGSGGGGSGGGGSGGGGSGGGGSEV QLVESGGGLVQPGGSLRLSCAASGYTFSSYWIEWVRQAPG KGLEWIGEILPGGGDTNYNEIFKGRATFSADTSKNTAYLQM NSLRAEDTAVYYCTRRVPIRLDYWGQGTLVTVSSPRASTT TPAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFAC DFWVLVVVGGVLACYSLLVTVAFIIFWVRSKRSRLLHSDY MNMTPRRPGPTRKHYQPYAPPRDFAAYRSRVKFSRSADAP AYKQGQNQLYNELNLGRREEYDVLDKRRGRDPEMGGKPR RKNPQEGLYNELQKDKMAEAYSEIGMKGERRRGKGHDGL YQGLSTATKDTYDALHMQALPPRRTDGSGATNFSLLKQAG DVEENPGPVSEAMPRGWTALCLLSLLPSGFMSLDNNGTAT PELPTQGTFSNVSTNVSYQETTTPSTLGSTSLHPVSQHGNEA TTNITETTVKFTSTSVITSVYGNTNSSVQSQTSVISTVFTTPA NVSTPETTLKPSLSPGNVSDLSTTSTSLATSPTKPYTSSSPILS DIKAEIKCSGIREVKLTQGICLEQNKTSSCAEFKKDRGEGLA RVLCGEEQADADAGAQVCSLLLAQSEVRPQCLLLVLANRT EISSKLQLMKKHQSDLKKLGILDFTEQDVASHQSYSQKTLI ALVTSGALLAVLGITGYFLMNRRSWSPTGEGGGGGFKRDL GGVKLPHLFGKRLVEARMASYPCHQHASAFDQAARSRGH SNRRTALRPRRQQEATEVRLEQKMPTLLRVYIDGPHGMGK TTTTQLLVALGSRDDIVYVPEPMTYWQVLGASETIANIYTT QHRLDQGEISAGDAAVVMTSAQITMGMPYAVTDAVLAPH VGGEAGSSHAPPPALTLLLDRHPIAVMLCYPAARYLMGSM TPQAVLAFVALIPPTLPGTNIVLGALPEDRHIDRLAKRQRPG ERLDLAMLAAIRRVYGLLANTVRYLQGGGSWWEDWGQL SGTAVPPQGAEPQSNAGPRPHIGDTLFTLFRAPELLAPNGD LYNVFAWALDVLAKRLRPMHVFILDYDQSPAGCRDALLQ LTSGMVQTHVTTPGSIPTICDLARTFAREMGEAN CD2-CAR- SEQ ID MALPVTALLLPLALLLHAARPDIVMTQAAPSVPVTPGESVS CD28_CD34 NO: 37 ISCRSSKTLLHSNGNTYLYWFLQRPGQSPQVLIYRMSNLAS GVPNRFSGSGSETTFTLRISRVEAEDVGIYYCMQHLEYPYT FGGGTKLEIERGGGGSGGGGSGGGGSGGGGSEVQLEESGA ELVRPGTSVKLSCKASGYTFTSYWMHWIKQRPEQGLEWIG RIDPYDSETHYNEKFKDKAILSVDKSSSTAYIQLSSLTSDDS AVYYCSRRDAKYDGYALDYWGQGTSVTVSSPRASTTTPA PRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDF WVLVVVGGVLACYSLLVTVAFIIFWVRSKRSRLLHSDYMN MTPRRPGPTRKHYQPYAPPRDFAAYRSRVKFSRSADAPAY KQGQNQLYNELNLGRREEYDVLDKRRGRDPEMGGKPRRK NPQEGLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQ GLSTATKDTYDALFIMQALPPRRTDGSGATNFSLLKQAGDV EENPGPVSEAMPRGWTALCLLSLLPSGFMSLDNNGTATPEL PTQGTFSNVSTNVSYQETTTPSTLGSTSLHPVSQHGNEATT NITETTVKFTSTSVITSVYGNTNSSVQSQTSVISTVFTTPANV STPETTLKPSLSPGNVSDLSTTSTSLATSPTKPYTSSSPILSDI KAEIKCSGIREVKLTQGICLEQNKTSSCAEFKKDRGEGLAR VLCGEEQADADAGAQVCSLLLAQSEVRPQCLLLVLANRTE ISSKLQLMKKHQSDLKKLGILDFTEQDVASHQSYSQKTLIA LVTSGALLAVLGITGYFLMNRRSWSPI CD2-CAR-4- SEQ ID MALPVTALLLPLALLLHAARPDIVMTQAAPSVPVTPGESVS 1BB_CD34 NO: 38 ISCRSSKTLLHSNGNTYLYWFLQRPGQSPQVLIYRMSNLAS GVPNRFSGSGSETTFTLRISRVEAEDVGIYYCMQHLEYPYT FGGGTKLEIERGGGGSGGGGSGGGGSGGGGSEVQLEESGA ELVRPGTSVKLSCKASGYTFTSYWMHWIKQRPEQGLEWIG RIDPYDSETHYNEKFKDKAILSVDKSSSTAYIQLSSLTSDDS AVYYCSRRDAKYDGYALDYWGQGTSVTVSSPRASTTTPA PRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDF WVLVVVGGVLACYSLLVTVAFIIFWVKRGRKKLLYIFKQP FMRPVQTTQEEDGCSCRFPEEEEGGCELRVKFSRSADAPAY KQGQNQLYNELNLGRREEYDVLDKRRGRDPEMGGKPRRK NPQEGLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQ GLSTATKDTYDALFIMQALPPRRTDGSGATNFSLLKQAGDV EENPGPVSEAMPRGWTALCLLSLLPSGFMSLDNNGTATPEL PTQGTFSNVSTNVSYQETTTPSTLGSTSLHPVSQHGNEATT NITETTVKFTSTSVITSVYGNTNSSVQSQTSVISTVFTTPANV STPETTLKPSLSPGNVSDLSTTSTSLATSPTKPYTSSSPILSDI KAEIKCSGIREVKLTQGICLEQNKTSSCAEFKKDRGEGLAR VLCGEEQADADAGAQVCSLLLAQSEVRPQCLLLVLANRTE ISSKLQLMKKHQSDLKKLGILDFTEQDVASHQSYSQKTLIA LVTSGALLAVLGITGYFLMNRRSWSPI CD3-CD28-CD34 SEQ ID MALPVTALLLPLALLLHAARPGSQVQLQQSGAELARPGAS NO: 39 VKMSCKASGYTFTRYTMHWVKQRPGQGLEWIGYINPSRG YTNYNQKFKDKATLTTDKSSSTAYMQLSSLTSEDSAVYYC ARYYDDHYCLDYWGQGTTLTVSSGGGGSGGGGSGGGGS GGGGSQIVLTQSPAIMSASPGEKVTMTCSASSSVSYMNWY QQKSGTSPKRWIYDTSKLASGVPAHFRGSGSGTSYSLTISG MEAEDAATYYCQQWSSNPFTFGSGTKLEINRPRASTTTPAP RPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDFW VLVVVGGVLACYSLLVTVAFIIFWVRSKRSRLLHSDYMNM TPRRPGPTRKHYQPYAPPRDFAAYRSRVKFSRSADAPAYK QGQNQLYNELNLGRREEYDVLDKRRGRDPEMGGKPRRKN PQEGLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQG LSTATKDTYDALHMQALPPRRTDGSGATNFSLLKQAGDVE ENPGPVSEAMPRGWTALCLLSLLPSGFMSLDNNGTATPELP TQGTFSNVSTNVSYQETTTPSTLGSTSLHPVSQHGNEATTNI TETTVKFTSTSVITSVYGNTNSSVQSQTSVISTVFTTPANVST PETTLKPSLSPGNVSDLSTTSTSLATSPTKPYTSSSPILSDIKA EIKCSGIREVKLTQGICLEQNKTSSCAEFKKDRGEGLARVL CGEEQADADAGAQVCSLLLAQSEVRPQCLLLVLANRTEISS KLQLMKKHQSDLKKLGILDFTEQDVASHQSYSQKTLIALV TSGALLAVLGITGYFLMNRRSWSPI

Tandem CAR-T Cells

[0183] A tandem CAR-T cell (tCAR-T), is a T cell with a single chimeric antigen polypeptide comprising two distinct extracellular ligand-binding (antigen/protein recognition) domains capable of interacting with two different cell surface molecules (e.g., antigen/protein), wherein the extracellular ligand-binding domains are linked together by one or more flexible linkers and share one or more costimulatory domains, wherein the binding of the first or second extracellular ligand-binding domain will signal through one or more the costimulatory domains(s) and a signaling transducing domain.

[0184] In certain embodiments, the T cell is deficient in one or more antigens or cell surface proteins (e.g., CD7 and CD2 for a CD7*CD2-tCAR.DELTA.CD7.DELTA.CD2 cell, or CD2 for a CD3*CD2-tCAR.DELTA.CD3.DELTA.CD2 cell). In non-limiting examples, the deficiency in the antigen(s) or cell surface protein(s) resulted from (a) modification of antigen or cell surface protein expressed by the T cell such that the chimeric antigen receptor no longer specifically binds the modified antigen(s) or cell surface protein(s) (e.g., the epitope of the one or more antigens recognized by the chimeric antigen receptor may be modified by one or more amino acid changes (e.g., substitutions or deletions) or the epitope may be deleted from the antigen), (b) modification of the T cell such that expression of antigen(s) or cell surface protein(s) is/are reduced in the T cell by at least 50%, at least 60%, at least 70%, at least 80%, at least 90% or more, or (c) modification of the T cell such that antigen(s) or cell surface protein(s) is/are not expressed (e.g., by deletion or disruption of the gene encoding antigen or cell surface protein). In each of the above embodiments, the CAR-T cell may be deficient in one or preferably all the antigens or cell surface proteins to which the chimeric antigen receptor specifically binds. The methods to genetically modify a T cell to be deficient in one or more antigens or cell surface proteins are well known in art and non-limiting examples are provided herein. In embodiments described below, the CRISPR-Cas9 system is used to modify a T cell to be deficient in one or more antigen(s) or cell surface protein(s). Any of these may be accomplished by the methods disclosed herein. In further embodiments, the T cell comprises a suicide gene.

[0185] A tCAR for a genome-edited, tandem CAR-T cell, i.e., CD2*CD3-tCART.DELTA.CD2.DELTA.CD3.epsilon., may be generated by cloning a commercially synthesized anti-CD2 single chain variable fragment (scFv) and an anti-CD3 single chain variable fragment (scFv), separated by a peptide linker, into a lentiviral vector containing, e.g., a 2.sup.nd or 3.sup.rd generation CAR backbone with CD28 and/or 4-1BB internal signaling domains. An extracellular hCD34 domain may be added after a P2A peptide to enable both detection of CAR following viral transduction and purification using anti-hCD34 magnetic beads. A similar method may be followed for making tCARs specific for other malignant T cell antigens.

[0186] Tandem CARs may have different linker structures, i.e., be linear or hairpin, and the hairpin linker may optionally comprise a (Cys=Cys) double-stranded bond (DSB).

[0187] A linear tandem CAR-T cell comprises a chimeric antigen receptor (CAR) polypeptide comprising a first signal peptide, a first extracellular ligand-binding domain, a second extracellular ligand-binding domain, a hinge region, a transmembrane domain, one or more co-stimulatory domains, and a signaling transducing domain, wherein the first extracellular ligand-binding antigen recognition domain and the second extracellular ligand-binding antigen recognition domain have affinities for different cell surface molecules, i.e., antigens on a cancer cell, for example, a malignant T cell, B cell, or plasma cell; and wherein the linear tandem CAR-T cell possesses one or more genetic modifications, deletions, or disruptions resulting in reduced expression of the cell surface molecules in the linear tandem CAR-T cell.

[0188] In another embodiment, the signal peptide is the signal peptide from human CD8.alpha..

[0189] In a third embodiment, the first extracellular ligand-binding domain comprises a single chain antibody fragment (scFv), comprising the light (V.sub.L) and the heavy (V.sub.H) variable fragment, designated V.sub.H1 and V.sub.L1 and joined by a linker (e.g., GGGGS (SEQ ID NO: 3065)). In some embodiments, this linker peptide is repeated 2, 3, 4, 5 or 6 times. In some embodiments, the first antigen recognition domain can be selected from: I) V.sub.H1--(GGGGS).sub.3-4 (SEQ ID NO: 3066)--V.sub.L1 or 2) V.sub.L1--(GGGGS).sub.3-4 (SEQ ID NO: 3066)--V.sub.H1.

[0190] In some embodiments, the second extracellular ligand-binding domain comprises a single chain antibody fragment (scFv), comprising the light (V.sub.L) and the heavy (V.sub.H) variable fragment, designated V.sub.H2 and V.sub.L2 and joined by a linker (e.g., GGGGS (SEQ ID NO: 3065)). In some embodiments, this linker peptide is repeated 2, 3, 4, 5 or 6 times. In some embodiments, the first antigen recognition domain can be selected from: 1) V.sub.H2--(GGGGS).sub.3-4 (SEQ ID NO: 3066)--V.sub.L2 or 2) V.sub.L2--(GGGGS).sub.3-4 (SEQ ID NO: 3066)--V.sub.H2.

[0191] In further embodiments, the first antigen recognition domain and second antigen recognition domain are connected by a short linker peptide of 5 amino acids (GGGGS (SEQ ID NO: 3065)). In some embodiments, this linker peptide is repeated 2, 3, 4, 5, or 6 times.

Tandem CAR Constructs

[0192] In one embodiment, the first extracellular ligand-binding domain antigen recognition comprises a single chain antibody fragment (scFv), comprising the heavy (V.sub.H) and the light (V.sub.L) variable fragment, designated V.sub.H1 and V.sub.L1, and joined by a linker (e.g., GGGGS (SEQ ID NO: 3065)), targets a cell surface molecule, i.e., an antigen expressed on a malignant cell.

[0193] In certain embodiments, the heavy (V.sub.H) and the light (V.sub.L) variable fragment, designated V.sub.H1 and V.sub.L1, targeting an antigen expressed on a malignant T cell is selected from BCMA, CS1, CD38, CD138, CD19, CD33, CD123, CD371, CD117, CD135, Tim-3, CD5, CD7, CD2, CD4, CD3, CD79A, CD79B, APRIL, CD56, and CD1a.

[0194] In certain embodiments, the second extracellular ligand-binding domain antigen recognition comprises a single chain antibody fragment (scFv), comprising the heavy (V.sub.H) and the light (V.sub.L) variable fragment, designated V.sub.H2 and V.sub.L2, and joined by a linker (e.g., GGGGS (SEQ ID NO: 3065)), and targets a cell surface molecule, i.e., an antigen, expressed on a malignant cell.

[0195] In certain embodiments, the heavy (V.sub.H) and the light (V.sub.L) variable fragments, designated V.sub.H2 and V.sub.L2, targeting an antigen expressed on a malignant T cell is selected from BCMA, CS1, CD38, CD138, CD19, CD33, CD123, CD371, CD117, CD135, Tim-3, CD5, CD7, CD2, CD4, CD3, CD79A, CD79B, APRIL, CD56, and CD1a and differs from the variable heavy (V.sub.H1) and light sequences (V.sub.L1) of the first extracellular ligand-binding domain of the CAR molecule.

[0196] Additional examples of tandem CARs are given below in Table 5.

TABLE-US-00005 TABLE 5 Tandem CARs and CAR-Ts Example Antigen Target CAR-T cell Antigen Deletion/Suppression T1 APRILxBCMA -- T2 APRILxCD19 -- T3 APRILxCD38 -- T4 APRILxCD38 CD38 T5 APRILx CS1 -- T6 APRILx CS1 CS1 T7 BCMAxCD19 -- T8 BCMAxCD38 -- T9 BCMAxCD38 CD38 T10 BCMAxCS1 -- T11 BCMAxCS1 CS1 T12 CD138xAPRIL T13 CD138xBCMA T14 CD138xCD19 T15 CD138xCD38 T16 CD138xCD38 CD38 T17 CD138xCD79A T18 CD138xCD79B T19 CD138xCS1 T20 CD138xCS1 CS1 T21 CD19xCD38 -- T22 CD19xCD38 CD3.epsilon. T23 CD2xCD3.epsilon. -- T24 CD2xCD3.epsilon. CD2 T25 CD2xCD3.epsilon. CD3.epsilon. T26 CD2xCD3.epsilon. CD2 and CD3.epsilon. T27 CD2xCD4 -- T28 CD2xCD4 CD2 T29 CD2xCD4 CD4 T30 CD2xCD4 CD2 and CD4 T31 CD2xCD4 CD2 and TRAC T32 CD2xCD4 CD4 and TRAC T33 CD2xCD4 CD2 and CD4 and TRAC T34 CD2xCD5 -- T35 CD2xCD5 CD2 T36 CD2xCD5 CD5 T37 CD2xCD5 CD2 and CD5 T38 CD2xCD5 CD2 and TRAC T39 CD2xCD5 CD5 and TRAC T40 CD2xCD5 CD2 and CD5 and TRAC T41 CD2xCD7 -- T42 CD2xCD7 CD2 T43 CD2xCD7 CD7 T44 CD2xCD7 CD2 and CD7 T45 CD2xCD7 CD2 and TRAC T46 CD2xCD7 CD7 and TRAC T47 CD2xCD7 CD2 and CD7 and TRAC T48 CD3.epsilon.xCD4 -- T49 CD3.epsilon.xCD4 CD3.epsilon. T50 CD3.epsilon.xCD4 CD4 T51 CD3.epsilon.xCD4 CD3.epsilon. and CD4 T52 CD3.epsilon.xCD5 -- T53 CD3.epsilon.xCD5 CD3.epsilon. T54 CD3.epsilon.xCD5 CD5 T55 CD3.epsilon.xCD5 CD3.epsilon. and CD5 T56 CD3.epsilon.xCD7 -- T57 CD3.epsilon.xCD7 CD3.epsilon. T58 CD3.epsilon.xCD7 CD7 T59 CD3.epsilon.xCD7 CD3.epsilon. and CD7 T60 CD4xCD5 -- T61 CD4xCD5 CD4 T62 CD4xCD5 CD5 T63 CD4xCD5 CD4 and CD5 T64 CD4xCD5 CD4 and TRAC T65 CD4xCD5 CD5 and TRAC T66 CD4xCD5 CD4 and CD5 and TRAC T67 CD4xCD7 -- T68 CD4xCD7 CD4 T69 CD4xCD7 CD7 T70 CD4xCD7 CD4 and CD7 T71 CD4xCD7 CD4 and TRAC T72 CD4xCD7 CD4 and TRAC T73 CD4xCD7 CD4 and CD7 and TRAC T74 CD5xCD7 -- T75 CD5xCD7 CD5 T76 CD5xCD7 CD7 T77 CD5xCD7 CD5 and CD7 T78 CD5xCD7 CD5 and TRAC T79 CD5xCD7 CD7 and TRAC T80 CD5xCD7 CD5 and CD7 and TRAC T81 CD79AxAPRIL T82 CD79AxBCMA T83 CD79AxCD19 T84 CD79AxCD38 T85 CD79AxCD38 CD38 T86 CD79AxCD79B T87 CD79AxCS1 T88 CD79AxCS1 CS1 T89 CD79BxAPRIL T90 CD79BxBCMA T91 CD79BxCD19 T92 CD79BxCD38 T93 CD79BxCD38 CD38 T94 CD79BxCD79A T95 CD79BxCS1 T96 CD79BxCS1 CS1 T97 CS1xCD19 -- T98 CS1xCD19 CS1 T99 CS1xCD38 -- T100 CS1xCD38 CS1 T101 CS1xCD38 CD38 T102 CS1xCD38 CS1 and CD38 T103 TCR.beta.xCD2 -- T104 TCR.beta.xCD2 TCR.beta. T105 TCR.beta.xCD2 CD2 T106 TCR.beta.xCD2 TCR.beta. and CD2 T107 TCR.beta.xCD3.epsilon. -- T108 TCR.beta.xCD3.epsilon. TCR.beta. T109 TCR.beta.xCD3.epsilon. CD3.epsilon. T110 TCR.beta.xCD3.epsilon. TCR.beta. and CD3.epsilon. T111 TCR.beta.xCD4 -- T112 TCR.beta.xCD4 TCR.beta. T113 TCR.beta.xCD4 CD4 T114 TCR.beta.xCD4 TCR.beta. and CD4 T115 TCR.beta.xCD5 -- T116 TCR.beta.xCD5 TCR.beta. T117 TCR.beta.xCD5 CD5 T118 TCR.beta.xCD5 TCR.beta. and CD5 T119 TCR.beta.xCD7 -- T120 TCR.beta.xCD7 TCR.beta. T121 TCR.beta.xCD7 CD7 T122 TCR.beta.xCD7 TCR.beta. and CD7 T123 TRACxCD2 -- T124 TRACxCD2 TRAC T125 TRACxCD2 CD2 T126 TRACxCD2 TRAC and CD2 T127 TRACxCD3.epsilon. -- T128 TRACxCD3.epsilon. TRAC T129 TRACxCD3.epsilon. CD3.epsilon. T130 TRACxCD3.epsilon. TRAC and CD3.epsilon. T131 TRACxCD4 -- T132 TRACxCD4 TRAC T133 TRACxCD4 CD4 T134 TRACxCD4 TRAC and CD4 T135 TRACxCD5 -- T136 TRACxCD5 TRAC T137 TRACxCD5 CD5 T138 TRACxCD5 TRAC and CD5 T139 TRACxCD7 -- T140 TRACxCD7 TRAC T141 TRACxCD7 CD7 T142 TRACxCD7 TRAC and CD7

[0197] In some embodiments, hairpin tandem CAR constructs may be provided herein, such as including, but not limited to, a construct incorporating the V.sub.H and V.sub.L domains of CD2 and CD3 scFvs (Table 6).

TABLE-US-00006 TABLE 6 Hairpin Tandem CAR Constructs Targeting CD2 and CD3. Clone 5 Clone 6 Clone 7 Clone 8 Clone 13 Clone 14 Clone 15 Clone 16 CD8a CD8a CD8a CD8a CD8a CD8a CD8a CD8a CD3-V.sub.L CD3-V.sub.L CD3-V.sub.L CD3-V.sub.L CD2-V.sub.L CD2-V.sub.L CD3-V.sub.L CD3-V.sub.L GGGGS.sub.4 GGGGS.sub.4 GGGGS.sub.4 GGGGS.sub.4 GGGGS.sub.4 GGGGS.sub.4 GGGGS.sub.4 GGGGS.sub.4 (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID NO: 9) NO: 9) NO: 9) NO: 9) NO: 9) NO: 9) NO: 9) NO: 9) CD2-V.sub.L CD2-V.sub.L CD2-V.sub.L CD2-V.sub.L CD3-V.sub.L CD3-V.sub.L CD2-V.sub.L CD2-V.sub.L (GGGGS).sub.10 (GGGGS).sub.4 (GGGGS).sub.10 (GGGGS).sub.4 (GGGGS).sub.10 (GGGGS).sub.4 (GGGGS).sub.10 (GGGGS).sub.4 (SEQ GGGG (SEQ GGGG (SEQ GGGG (SEQ GGGG ID NO: P(GGGGS).sub.4 ID NO: P(GGGGS).sub.4 ID NO: P(GGGGS).sub.4 ID NO: P(GGGGS).sub.4 3067) (SEQ 3067) (SEQ 3067) (SEQ 3067) (SEQ ID NO: ID NO: ID NO: ID NO: 3068) 3068) 3068) 3068) CD2-V.sub.H CD2-V.sub.H CD2-V.sub.H CD2-V.sub.H CD3-V.sub.H CD3-V.sub.H CD2-V.sub.H CD2-V.sub.H GGGGS.sub.4 GGGGS.sub.4 GGGGS.sub.4 GGGGS.sub.4 GGGGS.sub.4 GGGGS.sub.4 GGGGS.sub.4 GGGGS.sub.4 (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID (SEQ ID NO: 9) NO: 9) NO: 9) NO: 9) NO: 9) NO: 9) NO: 9) NO: 9) CD3-V.sub.H CD3-V.sub.H CD3-V.sub.H CD3-V.sub.H CD2-V.sub.H CD2-V.sub.H CD3-V.sub.H CD3-V.sub.H CD28 CD28 CD28 CD28 CD28 CD28 CD28 CD28 Tm Tm Tm Tm Tm Tm Tm Tm CD28 CD28 CD28 CD28 CD28 CD28 CD28 CD28 CD3z.sub.(1-2) CD3z.sub.(1-2) CD3z.sub.(1-2) CD3z.sub.(1-2) CD3z.sub.(1-2) CD3z.sub.(1-2) CD3z.sub.(1-2) CD3z.sub.(1-2) P2A P2A P2A P2A P2A P2A P2A P2A CD34 CD34 CD34 CD34 CD34 CD34 CD34 CD34

Dual CAR-T Cells

[0198] In certain embodiments, the disclosure provides an engineered T cell with two distinct chimeric antigen receptor polypeptides with affinity to different antigen(s) or cell surface protein(s) expressed within the same effector cell, wherein each CAR functions independently. The CAR may be expressed from single or multiple polynucleotide sequences that specifically bind different antigen(s) or cell surface protein(s), wherein the T cell is deficient in the antigen(s) or cell surface protein(s) to which the CARs bind (e.g., CD7*CD2-dCAR.DELTA.CD7ACD2 cell). In non-limiting examples, the deficiency in the antigen(s) or cell surface protein(s) resulted from (a) modification of antigen or cell surface protein expressed by the T cell such that the chimeric antigen receptor no longer specifically binds the modified antigen(s) or cell surface protein(s) (e.g., the epitope of the one or more antigens recognized by the chimeric antigen receptor may be modified by one or more amino acid changes (e.g., substitutions or deletions) or the epitope may be deleted from the antigen), (b) modification of the T cell such that expression of antigen(s) or cell surface protein(s) is/are reduced in the T cell by at least 50%, at least 60%, at least 70%, at least 80%, at least 90% or more, or (c) modification of the T cell such that antigen(s) or cell surface protein(s) is/are not expressed (e.g., by deletion or disruption of the gene encoding antigen or cell surface protein). In each of the above embodiments, the CAR-T cell may be deficient in one or preferably all the antigens or cell surface proteins to which the chimeric antigen receptor specifically binds. The methods to genetically modify a T cell to be deficient in one or more antigens or cell surface proteins are well known in art and non-limiting examples are provided herein. In embodiments described below, the CRISPR-Cas9 system is used to modify a T cell to be deficient in one or more antigen(s) or cell surface protein(s). Any of these may be accomplished by the methods disclosed herein. In further embodiments, the T cell comprises a suicide gene.

[0199] A dCAR for a genome-edited, dual CAR-T cell, i.e., CD2*CD3.epsilon.-dCART.DELTA.CD2.DELTA.CD3.epsilon., may be generated by cloning a commercially synthesized anti-CD2 single chain variable fragment into a lentiviral vector containing, e.g., a 2.sup.nd or 3.sup.rd generation CAR backbone with CD28 and/or 4-1BB internal signaling domains and cloning a commercially synthesized anti-CD3.epsilon. single chain variable into the same lentiviral vector containing an additional 2.sup.nd or 3.sup.rd generation CAR backbone with CD28 and/or 4-1BB internal signaling domains resulting in a plasmid from which the two CAR constructs are expressed from the same vector. An extracellular hCD34 domain may be added after a P2A peptide to enable both detection of CAR following viral transduction and purification using anti-hCD34 magnetic beads. A similar method may be followed for making tCARs specific for other malignant T cell antigens.

[0200] In a similar manner, other dual CARs may be constructed and are given below in Tables 5-7.

[0201] In one embodiment, a dual CAR-T cell comprises (i) a first chimeric antigen receptor (CAR) polypeptide comprising a first signal peptide, a first antigen recognition domain, a first hinge region, a first transmembrane domain, a first co-stimulatory domain, and a first signaling domain; and (ii) a second chimeric antigen receptor polypeptide comprising a second signaling peptide, a second antigen recognition domain, a second hinge region, a second transmembrane domain, a second co-stimulatory domain, and a second signaling domain; wherein the first antigen recognition domain and the second antigen recognition domain have affinities for different target antigens; and wherein the dual CAR-T cell possesses one or more genetic disruptions resulting in reduced expression of the target antigen in the dual CAR-T cell.

[0202] In a second embodiment, the first signal peptide is a CD8a signal sequence.

[0203] In a third embodiment, the first antigen recognition domain is fusion protein of the variable regions of immunoglobulin heavy and light chains, designated V.sub.H1 and V.sub.L1, for the first antigen recognition domain, connected by a short linker peptide of 5 amino acids (GGGGS).sub.3-4 (SEQ ID NO: 3065)). In some embodiments, this linker peptide is repeated 3 or 4 times. In some embodiments, the first antigen recognition domain can be selected from V.sub.H1--(GGGGS).sub.3-4 (SEQ ID NO: 3066)--V.sub.L1 or V.sub.L1--(GGGGS).sub.3-4 (SEQ ID NO: 3066)--V.sub.H1.

[0204] In some embodiments, the first hinge region comprises CD8a.

[0205] In some embodiments, the first transmembrane domain is CD8 or CD28.

[0206] In some embodiments, the first co-stimulatory domain comprises 4-1BB, CD28, or a combination of both, in either order, i.e., 4-1BB-CD28 or CD28-4-1BB.

[0207] In some embodiments, the first signaling domain is CD3.zeta. or a CD3.zeta. bi-peptide., i.e., CD3.zeta.-CD3.zeta..

[0208] In some embodiments, the second signal peptide is a CD8a signal sequence of SEQ NO:1.

[0209] In some embodiments, the second antigen recognition domain is fusion protein of the variable regions of immunoglobulin heavy and light chains, designated V.sub.H2 and V.sub.L2, for the second antigen recognition domain, connected by a short linker peptide of 5 amino acids (GGGGS (SEQ ID NO: 3065)). In some embodiments, this linker peptide is repeated 3 or 4 times. In some embodiments, the second antigen recognition domain can be selected from V.sub.H2--(GGGGS).sub.3-4 (SEQ ID NO: 3066)--V.sub.L2 or V.sub.L2--(GGGGS).sub.3-4 (SEQ ID NO: 3066)--V.sub.H2.

[0210] In some embodiments, the second hinge region comprises CD8a.

[0211] In some embodiments, the second transmembrane domain is CD8 or CD28.

[0212] In some embodiments, the second co-stimulatory domain comprises 4-1BB, CD28, or a combination of both, in either order, i.e., 4-1BB-CD28 or CD28-4-1BB.

[0213] In some embodiments, the second signaling domain is CD3.zeta. or a CD3.zeta. bi-peptide, i.e., CD3.zeta.-CD3.zeta..

[0214] In some embodiments, the CAR polypeptide comprises a first antigen recognition domain fusion protein of V.sub.H1--(GGGGS).sub.3-4 (SEQ ID NO: 3066)--V.sub.L1 and a second antigen recognition domain fusion protein of V.sub.H2--(GGGGS).sub.3-4 (SEQ ID NO: 3066)--V.sub.L2.

[0215] In some embodiments, the CAR polypeptide comprises a first antigen recognition domain fusion protein of V.sub.L1--(GGGGS).sub.3-4 (SEQ ID NO: 3066)--V.sub.H1 and a second antigen recognition domain fusion protein of V.sub.L2--(GGGGS).sub.3-4 (SEQ ID NO: 3066)--V.sub.H2.

[0216] In some embodiments, the CAR polypeptide comprises a first antigen recognition domain fusion protein of V.sub.H2--(GGGGS).sub.3-4 (SEQ ID NO: 3066)--V.sub.L2 and a second antigen recognition domain fusion protein of V.sub.H1--(GGGGS).sub.3-4 (SEQ ID NO: 3066)--V.sub.L1.

[0217] In some embodiments, the CAR polypeptide comprises a first antigen recognition domain fusion protein of V.sub.L2--(GGGGS).sub.3-4 (SEQ ID NO: 3066)--V.sub.H2 and a second antigen recognition domain fusion protein of V.sub.L1--(GGGGS).sub.3-4 (SEQ ID NO: 3066)--V.sub.H1.

[0218] In some embodiments, the CAR polypeptide comprises a first antigen recognition domain fusion protein of V.sub.H1--(GGGGS).sub.3-4 (SEQ ID NO: 3066)--V.sub.LI and a second antigen recognition domain fusion protein of V.sub.L2 (GGGGS).sub.3-4 (SEQ ID NO: 3066)--V.sub.H2.

[0219] In some embodiments, the CAR polypeptide comprises a first antigen recognition domain fusion protein of V.sub.L1--(GGGGS).sub.3-4 (SEQ ID NO: 3066)--V.sub.H1 and a second antigen recognition domain fusion protein of V.sub.H2--(GGGGS).sub.3-4 (SEQ ID NO: 3066)--V.sub.L2.

[0220] In some embodiments, the CAR polypeptide comprises a first antigen recognition domain fusion protein of V.sub.H2--(GGGGS).sub.3-4 (SEQ ID NO: 3066)--V.sub.L2 and a second antigen recognition domain fusion protein of V.sub.L1--(GGGGS).sub.3-4 (SEQ ID NO: 3066)--V.sub.H1.

[0221] In some embodiments, the CAR polypeptide comprises a first antigen recognition domain fusion protein of V.sub.L2--(GGGGS).sub.3-4 (SEQ ID NO: 3066)--V.sub.H2 and a second antigen recognition domain fusion protein of V.sub.H1 (GGGGS).sub.3-4 (SEQ ID NO: 3066)--V.sub.L1.

[0222] In some embodiments, the CAR polypeptide comprises at least one high efficiency cleavage site, wherein the high efficiency cleavage site is selected from P2A, T2A, E2A, and F2A.

[0223] In some embodiments, the CAR polypeptide comprises a suicide gene.

[0224] In some embodiments, the CAR polypeptide comprises a mutant cytokine receptor.

[0225] In some embodiments, the dual CAR-T cell targets two antigens selected from CD5, CD7, CD2, CD4, CD3, CD33, CD123 (IL3RA), CD371 (CLL-1; CLEC12A), CD117 (c-kit), CD135 (FLT3), BCMA, CS1, CD38, CD79A, CD79B, CD138, and CD19, APRIL, and TACI.

[0226] Additional examples of dual CARs are given below in Table 7.

TABLE-US-00007 TABLE 7 Dual CARs and dCAR-Ts Antigen Targets of CARs Antigen Deletion/ Example in dCAR-T cell Suppression D1 APRILxBCMA -- D2 APRILxCD19 -- D3 APRILxCD38 -- D4 APRILxCD38 CD38 D5 APRILxCS1 -- D6 APRILxCS1 CS1 D7 BCMAxCD19 -- D8 BCMAxCD38 -- D9 BCMAxCD38 CD38 D10 BCMAxC S1 -- D11 BCMAxC S1 CS1 D12 CD138xAPRIL D13 CD138xBCMA D14 CD138xCD19 D15 CD138xCD38 D16 CD138xCD38 CD38 D17 CD138xCD79A D18 CD138xCD79B D19 CD138xCS1 D20 CD138xCS1 CS1 D21 CD19xCD38 -- D22 CD19xCD38 CD38 D23 CD2xCD3.epsilon. -- D24 CD2xCD3.epsilon. CD2 D25 CD2xCD3.epsilon. CD3.epsilon. D26 CD2xCD3.epsilon. CD2 and CD3.epsilon. D27 CD2xCD4 -- D28 CD2xCD4 CD2 D29 CD2xCD4 CD4 D30 CD2xCD4 CD2 and CD4 D31 CD2xCD4 CD2 and TRAC D32 CD2xCD4 CD4 and TRAC D33 CD2xCD4 CD2 and CD4 and TRAC D34 CD2xCD5 -- D35 CD2xCD5 CD2 D36 CD2xCD5 CD5 D37 CD2xCD5 CD2 and CD5 D38 CD2xCD5 CD2 and TRAC D39 CD2xCD5 CD5 and TRAC D40 CD2xCD5 CD2 and CD5 and TRAC D41 CD2xCD7 -- D42 CD2xCD7 CD2 D43 CD2xCD7 CD7 D44 CD2xCD7 CD2 and CD7 D45 CD2xCD7 CD2 and TRAC D46 CD2xCD7 CD7 and TRAC D47 CD2xCD7 CD2 and CD7 and TRAC D48 CD3.epsilon.xCD4 -- D49 CD3.epsilon.xCD4 CD3.epsilon. D50 CD3.epsilon.xCD4 CD4 D51 CD3.epsilon.xCD4 CD3.epsilon. and CD4 D52 CD3.epsilon.xCD5 -- D53 CD3.epsilon.xCD5 CD3.epsilon. D54 CD3.epsilon.xCD5 CD5 D55 CD3.epsilon.xCD5 CD3.epsilon. and CD5 D56 CD3.epsilon.xCD7 -- D57 CD3.epsilon.xCD7 CD3.epsilon. D58 CD3.epsilon.xCD7 CD7 D59 CD3.epsilon.xCD7 CD3.epsilon. and CD7 D60 CD4xCD5 -- D61 CD4xCD5 CD4 D62 CD4xCD5 CD5 D63 CD4xCD5 CD4 and CD5 D64 CD4xCD5 CD4 and TRAC D65 CD4xCD5 CD5 and TRAC D66 CD4xCD5 CD4 and CD5 and TRAC D67 CD4xCD7 -- D68 CD4xCD7 CD4 D69 CD4xCD7 CD7 D70 CD4xCD7 CD4 and CD7 D71 CD4xCD7 CD4 and TRAC D72 CD4xCD7 CD7 and TRAC D73 CD4xCD7 CD4 and CD7 and TRAC D74 CD5xCD7 -- D75 CD5xCD7 CD5 D76 CD5xCD7 CD7 D77 CD5xCD7 CD5 and CD7 D78 CD5xCD7 CD5 and TRAC D79 CD5xCD7 CD7 and TRAC D80 CD5xCD7 CD5 and CD7 and TRAC D81 CD79AxAPRIL D82 CD79AxBCMA D83 CD79AxCD19 D84 CD79AxCD38 D85 CD79AxCD38 CD38 D86 CD79AxCD79B D87 CD79AxCS1 D88 CD79AxCS1 CS1 D89 CD79BxAPRIL D90 CD79BxBCMA D91 CD79BxCD19 D92 CD79BxCD38 D93 CD79BxCD38 CD38 D94 CD79BxCD79A D95 CD79BxCS1 D96 CD79BxCS1 CS1 D97 CS1xCD19 -- D98 CS1xCD19 CS1 D99 CS1xCD38 -- D100 CS1xCD38 CS1 D101 CS1xCD38 CD38 D102 CS1xCD38 CS1 and CD38 D103 TCR.beta.xCD2 -- D104 TCR.beta.xCD2 TCR.beta. D105 TCR.beta.xCD2 CD2 D106 TCR.beta.xCD2 TCR.beta. and CD2 D107 TCR.beta.xCD3.epsilon. -- D108 TCR.beta.xCD3.epsilon. TCR.beta. D109 TCR.beta.xCD3.epsilon. CD3.epsilon. D110 TCR.beta.xCD3.epsilon. TCR.beta. and CD3.epsilon. D111 TCR.beta.xCD4 -- D112 TCR.beta.xCD4 TCR.beta. D113 TCR.beta.xCD4 CD4 D114 TCR.beta.xCD4 TCR.beta. and CD4 D115 TCR.beta.xCD5 -- D116 TCR.beta.xCD5 TCR.beta. D117 TCR.beta.xCD5 CD5 D118 TCR.beta.xCD5 TCR.beta. and CD5 D119 TCR.beta.xCD7 -- D120 TCR.beta.xCD7 TCR.beta. D121 TCR.beta.xCD7 CD7 D122 TCR.beta.xCD7 TCR.beta. and CD7 D123 TRACxCD2 -- D124 TRACxCD2 TRAC D125 TRACxCD2 CD2 D126 TRACxCD2 TRAC and CD2 D127 TRACxCD3.epsilon. -- D128 TRACxCD3.epsilon. TRAC D129 TRACxCD3.epsilon. CD3.epsilon. D130 TRACxCD3.epsilon. TRAC and CD3.epsilon. D131 TRACxCD4 -- D132 TRACxCD4 TRAC D133 TRACxCD4 CD4 D134 TRACxCD4 TRAC and CD4 D135 TRACxCD5 -- D136 TRACxCD5 TRAC D137 TRACxCD5 CD5 D138 TRACxCD5 TRAC and CD5 D139 TRACxCD7 -- D140 TRACxCD7 TRAC D141 TRACxCD7 CD7 D142 TRACxCD7 TRAC and CD7

Cytokine/Chemokine/Transcription Factor Gene Deletion or Suppression

[0227] Cytokine release syndrome (CRS) is caused by a large, rapid release of cytokines from immune cells in response to immunotherapy (or other immunological stimulus). Accordingly, reducing the level of cytokines released would prevent or reduce the development and/or maintenance of CRS. As disclosed herein, this can be accomplished by modifying, disrupting, or deleting one or more cytokine/chemokine/transcription factor genes. One method to accomplish this is genetic ablation (gene silencing) in which gene expression is abolished through the alteration or deletion of genetic sequence information. This can be accomplished using known genetic engineering tools in the art such as Transcription Activator-like Effector Nucleases (TALENs), Zinc Finger Nucleases (ZFNs), CRISPR, and also by transfection of small interfering RNAs (siRNAs).

[0228] Another technique is expression of an scFv with an endoplasmic reticulum (ER) binding tether to bind the cytokine in the ER and prevent secretion. Specific constructs, named protein expression blockers (PEBLs), prevent transport of targeted proteins to the cell membrane. PEBL constructs can be readily combined with other gene modification systems for ex vivo cell processing of immune cells. A short hairpin RNA or small hairpin RNA (shRNA/Hairpin Vector) is an artificial RNA molecule with a tight hairpin turn that can be used to silence target gene expression, i.e., of antigens, via RNA interference (RNAi). Expression of shRNA in cells is typically accomplished by delivery of plasmids or through viral or bacterial vectors.

[0229] Cytokines or chemokines that can be deleted from immune effector cells as disclosed herein, e.g., by targeted transduction of a CAR into the gene sequence of the cytokine, include without limitation the following: XCL1, XCL2, CCL1, CCL2, CCL3, CCL4, CCLS, CCL7, CCL8, CCL11, CCL13, CCL14, CCL15, CCL16, CCL17, CCL18, CCL19, CCL20, CCL21, CCL22, CCL23, CCL24, CCL25, CCL26, CCL27, CXCL1, CXCL2, CXCL3, CXCL4, CXCL5, CXCL6, CXCL7, CXCL8, CXCL9, CXCL10, CXCL11, CXCL12, CXCL13, CXCL14, CX3CL1, IL-1.alpha., IL-1.beta., IL-1RA, IL-18, IL-2, IL-4, IL-7, IL-9, IL-13, IL-15, IL-3, IL-5, GM-CSF, IL-6, IL-11, G-CSF, IL-12, LIF, OSM, IL-10, IL-20, IL-14, IL-16, IL-17, IFN-.alpha., IFN-.gamma., CD154, LT-.beta., TNF-.alpha., TNF-.beta., 4-1BBL, APRIL, CD70, CD153, CD178, GITRL, LIGHT, OX40L, TALL-1, TRAIL, TWEAK, TRANCE, TGF-62 1, TGF-.beta.2, TGF-.beta.3, Epo, Tpo, Flt-3L, SCF, M-CSF, MSP, A2M, ACKR1, ACKR2, ACKR3, ACVR1, ACVR2B, ACVRL1, ADIPOQ, AGER, AGRN, AIMP1, AREG, BMP1, BMP10, BMP15, BMP2, BMP3, BMP4, BMP5, BMP6, BMP7, BMP8A, BMP8B, BMPR2, C10orf99, C1QTNF4, C5, CCL28, CCR1, CCR2, CCR3, CCR5, CCR6, CCR7, CD109, CD36, CD4, CD40LG, CD74, CER1, CHRD, CKLF, CLCF1, CMTM1, CMTM2, CMTM3, CMTM4, CMTM5, CMTM6, CMTM7, CMTM8, CNTF, CNTFR, COPS5, CRLF1, CSF1, CSF1R, CSF2, CSF3, CSF3R, CTF1, CX3CR1, CXCL16, CXCL17, CXCR1, CXCR2, CXCR3, CXCR4, CXCR6, EBI3, EDN1, ELANE, ENG, FAM3B, FAM3C, FAM3D, FAS, FASLG, FGF2, FLT3LG, FZD4, GBP1, GDF1, GDF10, GDF11, GDF15, GDF2, GDF3, GDF5, GDF6, GDF7, GDF9, GPI, GREM1, GREM2, GRN, HAX1, HFE2, HMGB1, HYAL2, IFNA10, IFNA14, IFNA16, IFNA2, IFNA5, IFNA6, IFNA8, IFNAR1, IFNAR2, IFNB1, IFNE, IFNG, IFNGR1, IFNK, IFNL1, IFNL3, IFNW1, IL10RA, IL11RA, IL12A, IL12B, IL12RB1, IL17A, IL17B, IL17C, IL17D, IL17F, IL18BP, IL-19, IL1F10, IL1R1, IL1R2, IL1RAPL1, IL1RL1, IL1RN, IL20RA, IL20RB, IL21, IL22, IL22RA1, IL22RA2, IL23A, IL23R, IL24, IL25, IL26, IL27, IL2RA, IL2RB, IL2RG, IL31, IL31RA, IL32, IL33, IL34, IL36A, IL36B, IL36G, IL36RN, IL37, IL6R, IL6ST, INHA, INHBA, INHBB, INHBC, INHBE, ITGA4, ITGAV, ITGB1, ITGB3, KIT, KITLG, KLHL20, LEFTY1, LEFTY2, LIFR, LTA, LTB, LTBP1, LTBP3, LTBP4, MIF, MINOS1-, MSTN, NAMPT, NBL1, NDP, NLRP7, NODAL, NOG, NRG1, NRP1, NRP2, OSMR, PARK7, PDPN, PF4, PF4V1, PGLYRP1, PLP2, PPBP, PXDN, SCG2, SCGB3A1, SECTM1, SLURP1, SOSTDC1, SP100, SPP1, TCAP, TGFBR1, TGFBR2, TGFBR3, THBS1, THNSL2, THPO, TIMP1, TNF, TNFRSF11, TNFRSF1A, TNFRSF9, TNFRSF10, TNF SF11, TNFSF12, TNFSF12-, TNFSF13, TNFSF13B, TNFSF14, TNFSF15, TNFSF18, TNFSF4, TNFSF8, TNFSF9, TRIM16, TSLP, TWSG1, TXLNA, VASN, VEGFA, VSTM1, WFIKKN1, WFIKKN2, WNT1, WNT2, WNTSA, WNT7A, and ZFP36.

[0230] In some embodiments, the cytokine is chosen from cytokine is chosen from MCP1 (CCL2), MCP-2, GM-CSF, G-CSF, M-CSF, Il-4, and IFN.gamma..

[0231] In certain embodiments, transcription factors that can be deleted from immune effector cells as disclosed herein include AHR, BCL6, FOXP3, GATA3, MAF, RORC, SPI1, and TBX21.

[0232] The sequences of these genes are known and available in the art and can include, for example, those provided in Table 10.

Selection of Priority Target Genes

[0233] Cytokine/chemokine gene targets of specific interest for deletion or suppression (e.g., ablation, knock-out, KO) in CAR-T cells for the mitigation of CRS have been categorized into groups based on biological function. CRS development is dependent upon CAR-T cell activation and subsequent cytokine release, which initiates a dysregulated immune system in the recipient of the CAR-T cell therapy. Several studies have indicated that recipient myeloid activation is necessary for the development of CRS.

[0234] The first group of potential genes to KO in CAR-T are surface receptors that, when engaged with myeloid cells in normal immunological responses activate the myeloid cells (e.g., CD40L). The second group are cytokines that are released from CAR-T cells that activate myeloid cells (e.g., GM-CSF). In both these categories, the goal is to prevent CAR-T cell signaling, which will activate recipient myeloid cells and initiate CRS.

[0235] The third category of targets are endogenous T cell receptors that increase T cell activation (potentially in the absence of tumor target) that are integrated into the CAR-T receptor (e.g., endogenous CD28). The aim is to curtail activation of the CAR-T from non-tumor interactions, such as activated myeloid cells that could engage with CD28 on activated T cells, thus amplifying T cell cytokine production and subsequent myeloid activation.

[0236] The fourth and fifth categories of gene KO targets are transcription factors and cytokines that drive CAR-T cell differentiation and subsequent functional characteristics. CAR-T cells that are phenotypically similar to normal cytotoxic T cells (CTL, typically identified by CD8 expression) are capable of direct tumor killing through T cell mediated effector functions. CTL are supported and maintained by T helper cells (expressing CD4). Importantly, subsets of T helper cells can support CTL (i.e., Thl cells) or inhibit (i.e., Th2 cells). Other T cells, such as Tregs can also inhibit CTL development and function. The aim is to target cytokines or transcription factors in the CAR-T population that would lead to CAR-T differentiation into non-cytotoxic T cell populations. Additionally, Th2 cells produce cytokines (such as GM-CSF and IL-4), which are indicative markers of CRS. It is likely that CAR-T phenotypes, which cannot optimally kill tumor cells, will be activated via CAR-T receptors, produce signals that drive CRS in the host, increase the time required for tumor killing, and require higher CAR-T cell doses than optimized "killing" products. Thus, knocking out or ablating (or suppressing) transcription factors (such as GATA3) or cytokines (such as IL-4) will prevent (or reduce) Th2 bias and reduce CRS.

[0237] Of additional interest regarding both myeloid activating cytokines and optimized CAR-T cell differentiation is the potential to mitigate CAR-T neurotoxicity. Neurotoxicity occurs in a small population of CAR-T recipients with CRS. Research has shown that CRS patients that progress to develop neurotoxicity have increased IL-5 and ferritin levels (Santomasso et al., 2017 and Philip et al., 2019). These two biomarkers indicate that mast cell activation may be involved with CNS complications. IL-5 is a key cytokine produced by Th2 cells, eosinophils and mast cells. Excessive levels of ferritin are observed in mastocytosis and several diseases involving mast cell dysregulation. Additionally, many mast cell diseases include neurological dysregulation. Given raised levels of IL-5, ferritin, and neurological toxicity in some patients, reducing mast cell activation by cytokines such as IL-5, or preventing Th2 cell development which drives IL-5-dependent mast cell activation, may also mitigate neurological complications seen in CRS recipients. With respect to CNS complications, CX3CR1 and OX40 were also highlighted, due to previously demonstrated high T cell burden in the CNS. CX3CR1 is a T cell chemokine receptor that principally directs T cells and potentially CAR-T cells into the CNS. OX40 is the T cell receptor which facilitates activation by cell-cell interaction with OX40L on eosinophils and mast cells.

[0238] Thus, in certain embodiments, the cytokine is chosen from CCL2 (MCP1), MCP-2, GM-CSF, G-CSF, M-CSF, Il-4, and IFN.gamma..

[0239] Indications and Standards of Care in CAR-T Therapy

[0240] In some embodiment, the genome-edited immune effector cells disclosed herein, and/or generated using the methods disclosed herein, express one or more chimeric antigen receptors (CARs) and can be used as a medicament, i.e., for the treatment of disease. In many embodiments, the cells are CAR-T cells.

[0241] Cells disclosed herein, and/or generated using the methods disclosed herein, may be used in immunotherapy and adoptive cell transfer, for the treatment, or the manufacture of a medicament for treatment, of cancers, autoimmune diseases, infectious diseases, and other conditions.

[0242] The cancer may be a hematologic malignancy or solid tumor. Hematologic malignancies include leukemias, lymphomas, multiple myeloma, and subtypes thereof. Lymphomas can be classified various ways, often based on the underlying type of malignant cell, including Hodgkin's lymphoma (often cancers of Reed-Sternberg cells, but also sometimes originating in B cells; all other lymphomas are non-Hodgkin's lymphomas), B-cell lymphomas, T-cell lymphomas, mantle cell lymphomas, Burkitt's lymphoma, follicular lymphoma, and others as defined herein and known in the art.

[0243] B-cell lymphomas include, but are not limited to, diffuse large B-cell lymphoma (DLBCL), chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL), and others as defined herein and known in the art.

[0244] T-cell lymphomas include T-cell acute lymphoblastic leukemia/lymphoma (T-ALL), peripheral T-cell lymphoma (PTCL), T-cell chronic lymphocytic leukemia (T-CLL) Sezary syndrome, and others as defined herein and known in the art.

[0245] Leukemias include Acute myeloid (or myelogenous) leukemia (AML), chronic myeloid (or myelogenous) leukemia (CML), acute lymphocytic (or lymphoblastic) leukemia (ALL), chronic lymphocytic leukemia (CLL) hairy cell leukemia (sometimes classified as a lymphoma), and others as defined herein and known in the art.

[0246] Plasma cell malignancies include lymphoplasmacytic lymphoma, plasmacytoma, and multiple myeloma.

[0247] In some embodiments, the medicament can be used for treating cancer in a patient, particularly for the treatment of solid tumors such as melanomas, neuroblastomas, gliomas or carcinomas such as tumors of the brain, head and neck, breast, lung (e.g., non small cell lung cancer, NSCLC), reproductive tract (e.g., ovary), upper digestive tract, pancreas, liver, renal system (e.g., kidneys), bladder, prostate and colorectum.

[0248] In another embodiment, the medicament can be used for treating cancer in a patient, particularly for the treatment of hematologic malignancies selected from multiple myeloma and acute myeloid leukemia (AML) and for T-cell malignancies selected from T-cell acute lymphoblastic leukemia (T-ALL), non-Hodgkin's lymphoma, and T-cell chronic lymphocytic leukemia (T-CLL).

[0249] In some embodiments, the cells may be used in the treatment of autoimmune diseases such as lupus, autoimmune (rheumatoid) arthritis, multiple sclerosis, transplant rejection, Crohn's disease, ulcerative colitis, dermatitis, and the like. In some embodiments, the cells are chimeric autoantibody receptor T-cells, or CAAR-Ts displaying antigens or fragments thereof, instead of antibody fragments; in this version of adoptive cell transfer, the B cells that cause autoimmune diseases will attempt to attack the engineered T cells, which will respond by killing them.

[0250] In some embodiments, the cells may be used in the treatment of infectious diseases such as HIV and tuberculosis.

[0251] In another embodiment, the CAR-T cells of the present disclosure can undergo robust in vivo T cell expansion and can persist for an extended amount of time.

[0252] In some embodiments, the treatment of a patient with CAR-T cells of the present disclosure can be ameliorating, curative or prophylactic. It may be either part of an autologous immunotherapy or part of an allogenic immunotherapy treatment. By autologous, it is meant that cells, cell line or population of cells used for treating patients are originating from said patient or from a Human Leucocyte Antigen (HLA) compatible donor. By allogeneic, is meant that the cells or population of cells used for treating patients are not originating from the patient but from a donor.

[0253] The treatment of cancer with CAR-T cells of the present disclosure may be in combination with one or more therapies selected from antibody therapy, chemotherapy, cytokine therapy, dendritic cell therapy, gene therapy, hormone therapy, radiotherapy, laser light therapy, and radiation therapy.

[0254] The administration of CAR-T cells or a population of CAR-T cells of the present disclosure of the present disclosure be carried out by aerosol inhalation, injection, ingestion, transfusion, implantation or transplantation. The CAR-T cells compositions described herein, i.e., mono CAR, dual CAR, tandem CARs, may be administered to a patient subcutaneously, intradermally, intratumorally, intranodally, intramedullary, intramuscularly, by intravenous or intralymphatic injection, or intraperitoneally. In one embodiment, the cell compositions of the present disclosure are preferably administered by intravenous injection.

[0255] The administration of CAR-T cells or a population of CAR-T cells can consist of the administration of 10.sup.4-10.sup.9 cells per kg body weight, preferably 10.sup.5 to 10.sup.6 cells/kg body weight including all integer values of cell numbers within those ranges. The CAR-T cells or a population of CAR-T cells can be administrated in one or more doses. In another embodiment, the effective amount of CAR-T cells or a population of CAR-T cells are administrated as a single dose. In another embodiment, the effective amount of cells are administered as more than one dose over a period time. Timing of administration is within the judgment of a health care provider and depends on the clinical condition of the patient. The CAR-T cells or a population of CAR-T cells may be obtained from any source, such as a blood bank or a donor. While the needs of a patient vary, determination of optimal ranges of effective amounts of a given CAR-T cell population(s) for a particular disease or conditions are within the skill of the art. An effective amount means an amount which provides a therapeutic or prophylactic benefit. The dosage administered will be dependent upon the age, health and weight of the patient recipient, type of concurrent treatment, if any, frequency of treatment, and the nature of the effect desired.

[0256] In another embodiment, the effective amount of CAR-T cells or a population of CAR-T cells or composition comprising those CAR-T cells are administered parenterally. The administration can be an intravenous administration. The administration of CAR-T cells or a population of CAR-T cells or composition comprising those CAR-T cells can be directly done by injection within a tumor.

[0257] In one embodiment of the present disclosure, the CAR-T cells or a population of the CAR-T cells are administered to a patient in conjunction with, e.g., before, simultaneously or following, any number of relevant treatment modalities, including but not limited to, treatment with cytokines, or expression of cytokines from within the CAR-T, that enhance T-cell proliferation and persistence and, include but not limited to, IL-2, IL-7, and IL-15.

[0258] In a second embodiment, the CAR-T cells or a population of CAR-T cells of the present disclosure may be used in combination with agents that inhibit immunosuppressive pathways, including but not limited to, inhibitors of TGF-.beta., interleukin 10 (IL-10), adenosine, VEGF, indoleamine 2,3 dioxygenase 1 (IDO1), indoleamine 2,3-dioxygenase 2 (IDO2), tryptophan 2-3-dioxygenase (TDO), lactate, hypoxia, arginase, and prostaglandin E2.

[0259] In another embodiment, the CAR-T cells or a population of CAR-T cells of the present disclosure may be used in combination with T-cell checkpoint inhibitors, including but not limited to, anti-CTLA4 (Ipilimumab) anti-PD1 (Pembrolizumab, Nivolumab, Cemiplimab), anti-PDL1 (Atezolizumab, Avelumab, Durvalumab), anti-PDL2, anti-BTLA, anti-LAG3, anti-TIM3, anti-VISTA, anti-TIGIT, and anti-KIR.

[0260] In another embodiment, the CAR-T cells or a population of CAR-T cells of the present disclosure may be used in combination with T cell agonists, including but not limited to, antibodies that stimulate CD28, ICOS, OX-40, CD27, 4-1BB, CD137, GITR, and HVEM

[0261] In another embodiment, the CAR-T cells or a population of CAR-T cells of the present disclosure may be used in combination with therapeutic oncolytic viruses, including but not limited to, retroviruses, picornaviruses, rhabdoviruses, paramyxoviruses, reoviruses, parvoviruses, adenoviruses, herpesviruses, and poxviruses.

[0262] In another embodiment, the CAR-T cells or a population of CAR-T cells of the present disclosure may be used in combination with immunostimulatory therapies, such as toll-like receptors agonists, including but not limited to, TLR3, TLR4, TLR7 and TLR9 agonists.

[0263] In another embodiment, the CAR-T cells or a population of CAR-T cells of the present disclosure may be used in combination with stimulator of interferon gene (STING) agonists, such as cyclic GMP-AMP synthase (cGAS).

[0264] Immune effector cell aplasia, particularly T cell aplasia is also a concern after adoptive cell transfer therapy. When the malignancy treated is a T-cell malignancy, and CAR-T cells target a T cell antigen, normal T cells and their precursors expressing the antigen will become depleted, and the immune system will be compromised. Accordingly, methods for managing these side effects are attendant to therapy. Such methods include selecting and retaining non-malignant T cells or precursors, either autologous or allogeneic (optionally engineered not to cause rejection or be rejected), for later expansion and re-infusion into the patient, after CAR-T cells are exhausted or deactivated. Alternatively, CAR-T cells which recognize and kill subsets of TCR-bearing cells, such as normal and malignant TRBC1.sup.+, but not TRBC2.sup.+ cells, or alternatively, TRBC2.sup.+, but not TRBC1.sup.+ cells, may be used to eradicate a T cell malignancy while preserving sufficient normal T cells to maintain normal immune system function.

Definitions

[0265] As used herein, the terms below have the meanings indicated. Other definitions may occur throughout the specification.

[0266] When ranges of values are disclosed, and the notation "from n.sub.1 . . . to n.sub.2" or "between n.sub.1 . . . and n.sub.2" is used, where n.sub.1 and n.sub.2 are the numbers, then unless otherwise specified, this notation is intended to include the numbers themselves and the range between them. This range may be integral or continuous between and including the end values. By way of example, the range "from 2 to 6 carbons" is intended to include two, three, four, five, and six carbons, since carbons come in integer units. Compare, by way of example, the range "from 1 to 3 .mu.M (micromolar)," which is intended to include 1 .mu.M, 3 .mu.M, and everything in between to any number of significant figures (e.g., 1.255 .mu.M, 2.1 .mu.M, 2.9999 .mu.M, etc.).

[0267] The term "about," as used herein, is intended to qualify the numerical values which it modifies, denoting such a value as variable within a margin of error. When no particular margin of error, such as a standard deviation to a mean value given in a chart or table of data, is recited, the term "about" should be understood to mean that range which would encompass the recited value and the range which would be included by rounding up or down to that figure as well, taking into account significant figures.

[0268] The term "activation" (and other conjugations thereof) in reference to cells is generally understood to be synonymous with "stimulating" and as used herein refers to treatment of cells that results in expansion of cell populations. In T cells, activation is often accomplished by exposure to CD2 and CD28 (and sometimes CD2 as well) agonists, typically antibodies, optionally coated onto magnetic beads or conjugated to a colloidal polymeric matrix.

[0269] The term "antigen" as used herein is a cell surface protein recognized by (i.e., that is the target of) T cell receptor or chimeric antigen receptor. In the classical sense antigens are substances, typically proteins, that are recognized by antibodies, but the definitions overlap insofar as the CAR comprises antibody-derived domains such as light (V.sub.L) and heavy (V.sub.H) chains recognizing one or more antigen(s).

[0270] The term "cancer" refers to a malignancy or abnormal growth of cells in the body. Many different cancers can be characterized or identified by particular cell surface proteins or molecules. Thus, in general terms, cancer in accordance with the present disclosure may refer to any malignancy that may be treated with an immune effector cell, such as a CAR-T cell as described herein, in which the immune effector cell recognizes and binds to the cell surface protein on the cancer cell. As used herein, cancer may refer to a hematologic malignancy, such as multiple myeloma, a T-cell malignancy, or a B cell malignancy. T cell malignancies may include, but are not limited to, T-cell acute lymphoblastic leukemia (T-ALL) or non-Hodgkin's lymphoma. A cancer may also refer to a solid tumor, such as including, but not limited to, cervical cancer, pancreatic cancer, ovarian cancer, mesothelioma, and lung cancer.

[0271] A "cell surface protein" as used herein is a protein (or protein complex) expressed by a cell at least in part on the surface of the cell. Examples of cell surface proteins include the TCR (and subunits thereof) and CD7.

[0272] The term "combination therapy" means the administration of two or more therapeutic agents to treat a therapeutic condition or disorder described in the present disclosure. Such administration encompasses co-administration of these therapeutic agents in a substantially simultaneous manner, such as in a single capsule having a fixed ratio of active ingredients or in multiple, separate capsules for each active ingredient. In addition, such administration also encompasses use of each type of therapeutic agent in a sequential manner. In either case, the treatment regimen will provide beneficial effects of the drug combination in treating the conditions or disorders described herein.

[0273] The term "composition" as used herein refers to an immunotherapeutic cell population combination with one or more therapeutically acceptable carriers.

[0274] The term "disease" as used herein is intended to be generally synonymous, and is used interchangeably with, the terms "disorder," "syndrome," and "condition" (as in medical condition), in that all reflect an abnormal condition of the human or animal body or of one of its parts that impairs normal functioning, is typically manifested by distinguishing signs and symptoms, and causes the human or animal to have a reduced duration or quality of life.

[0275] The term "donor template" refers to the reference genomic material that the cell uses as a template to repair the a double-stranded break through the homology-directed repair (HDR) DNA repair pathway. The donor template contains the piece of DNA to be inserted into the genome (containing the gene to be expressed, CAR, or marker) with two homology arms flanking the site of the double-stranded break. In some embodiments, a donor template may be an adeno-associated virus, a single-stranded DNA, or a double-stranded DNA.

[0276] The term "fratricide" as used herein means a process which occurs when a CAR-T cell (or other CAR-bearing immune effector cell) becomes the target of, and is killed by, another CAR-T cell comprising the same chimeric antigen receptor as the target of CAR-T cell, because the targeted cell expresses the antigen specifically recognized by the chimeric antigen receptor on both cells. CAR-T comprising a chimeric antigen receptor which are deficient in an antigen to which the chimeric antigen receptor specifically binds will be "fratricide-resistant."

[0277] The term "genome-edited" or "gene-edited" as used herein means having a gene or potion of the genome added, deleted, or modified (e.g., disrupted) to be non-functional. Thus, in certain embodiments, a "genome-edited T cell" is a T cell that has had a gene such as a CAR recognizing at least one antigen added; and/or has had a gene such as the gene(s) to the antigen(s) that are recognized by the CAR deleted, and/or has had the gene to the TCR or a subunit thereof disrupted.

[0278] A "healthy donor," as used herein, is one who does not have a malignancy (particularly a hematologic malignancy, e.g., a T-cell malignancy).

[0279] As used herein, an "immature dendritic cell" or "iDC" refers to an immature dendritic cell.

[0280] The term "therapeutically acceptable" refers to substances which are suitable for use in contact with the tissues of patients without undue toxicity, irritation, and allergic response, are commensurate with a reasonable benefit/risk ratio, and/or are effective for their intended use.

[0281] The term "therapeutically effective" is intended to qualify the amount of active ingredients used in the treatment of a disease or disorder or on the effecting of a clinical endpoint.

[0282] The term "patient" is generally synonymous with the term "subject" and includes all mammals including humans.

[0283] A "malignant B cell" is a B cell derived from a B-cell malignancy. B cell malignancies include, without limitation, (DLBCL), chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL), and B cell-precursor acute lymphoblastic leukemia (ALL).

[0284] The term "exposing to," as used herein, in the context of bringing compositions of matter (such as antibodies) into intimate contact with other compositions of matter (such as cells), is intended to be synonymous with "incubated with," and no lengthier period of time in contact is intended by the use of one term instead of the other.

[0285] A "malignant T cell" is a T cell derived from a T-cell malignancy. The term "T-cell malignancy" refers to a broad, highly heterogeneous grouping of malignancies derived from T-cell precursors, mature T cells, or natural killer cells. Non-limiting examples of T-cell malignancies include T-cell acute lymphoblastic leukemia/lymphoma (T-ALL), human T-cell leukemia virus type 1-positive (HTLV-1+) adult T-cell leukemia/lymphoma (ATL), T-cell prolymphocytic leukemia (T-PLL), Adult T-cell lymphoma/leukemia (HTLV-1 associated), Aggressive NK-cell leukemia, Anaplastic large-cell lymphoma (ALCL), ALK positive, Anaplastic large-cell lymphoma (ALCL), ALK negative, Angioimmunoblastic T-cell lymphoma (AITL), Breast implant-associated anaplastic large-cell lymphoma, Chronic lymphoproliferative disorder of NK cells, Extra nodal NK/T-cell lymphoma, nasal type, Enteropathy-type T-cell lymphoma, Follicular T-cell lymphoma, Hepatosplenic T-cell lymphoma, Indolent T-cell lymphoproliferative disorder of the GI tract, Monomorphic epitheliotrophic intestinal T-cell lymphoma, Mycosis fungoides, Nodal peripheral T-cell lymphoma with TFH phenotype, Peripheral T-cell lymphoma (PTCL), NOS, Primary cutaneous .alpha./.beta. T-cell lymphoma, Primary cutaneous CD8+ aggressive epidermotropic cytotoxic T-cell lymphoma, Primary cutaneous acral CD8+ T-cell lymphoma, Primary cutaneous CD4+ small/medium T-cell lymphoproliferative disorders [Primary cutaneous anaplastic large-cell lymphoma (C-ALCL), lymphoid papulosis], Sezary syndrome, Subcutaneous, panniculitis-like T-cell lymphoma, Systemic EBV+ T-cell lymphoma of childhood, and T-cell large granular lymphocytic leukemia (LGL).

[0286] A "malignant plasma cell" is a plasma cell derived from a plasma cell malignancy. The term "plasma-cell malignancy" refers to a malignancy in which abnormal plasma cells are overproduced. Non-limiting examples of plasma cell malignancies include lymphoplasmacytic lymphoma, plasmacytoma, and multiple myeloma.

[0287] As used herein, "suicide gene" refers to a nucleic acid sequence introduced to a CAR-T cell by standard methods known in the art, that when activated result in the death of the CAR-T cell. If required suicide genes may facilitate the tracking and elimination, i.e., killing, of CAR-T cells in vivo. Facilitated killing of CAR-T cells by activating a suicide gene can be accomplished by standard methods known in the art. Suicide gene systems known in the art include, but are not limited to, several herpes simplex virus thymidine kinase (HSVtk)/ganciclovir (GCV) suicide gene therapy systems and inducible caspase 9 proteins. In one embodiment, the suicide gene is a chimeric CD34/thymidine kinase.

[0288] As used herein, an "immune effector cell" is a leukocyte that can modulate an immune response. Immune effector cells include T cells, B cells, natural killer (NK) cells, iNKT cells (invariant T-cell receptor alpha natural killer T cells), and macrophages. T cell receptor (TCR)-bearing immune effector cells include, of course, T cells, but also cells which have been engineered to express a T cell receptor. Immune effector cells may be obtained or derived/generated from any appropriate source, such as including, but not limited to, healthy donors, peripheral blood mononuclear cells, cord blood, and induced pluripotent stem cells (iPSC).

[0289] As used herein, a "CAR-bearing immune effector cell" is an immune effector cell which has been transduced with at least one CAR. A "CAR-T cell" is a T cell which has been transduced with at least one CAR; CAR-T cells can be mono, dual, or tandem CAR-T cells. CAR-T cells can be autologous, meaning that they are engineered from a subject's own cells, or allogeneic, meaning that the cells are sourced from a healthy donor, and in many cases, engineered so as not to provoke a host-vs-graft or graft-vs-host reaction.

[0290] A "chimeric antigen receptor" or "CAR" as used herein and generally used in the art, refers to a recombinant fusion protein that has an extracellular ligand-binding domain, a transmembrane domain, and a signaling transducing domain that directs the cell to perform a specialized function upon binding of the extracellular ligand-binding domain to a component present on the target cell. For example, a CAR can have an antibody-based specificity for a desired antigen (e.g., tumor antigen) with a T cell receptor-activating intracellular domain to generate a chimeric protein that exhibits specific anti-target cellular immune activity. First-generation CARs include an extracellular ligand-binding domain and signaling transducing domain, commonly CD3.zeta. or Fc.epsilon.RI.gamma.. Second generation CARs are built upon first generation CAR constructs by including an intracellular costimulatory domain, commonly 4-1BB or CD28. These costimulatory domains help enhance CAR-T cell cytotoxicity and proliferation compared to first generation CARs. The third generation CARs include multiple costimulatory domains, primarily to increase CAR-T cell proliferation and persistence. Chimeric antigen receptors are distinguished from other antigen binding agents by their ability both to bind MHC-independent antigens and transduce activation signals via their intracellular domain.

[0291] The term "CAR-iNKT cell" (equivalently, iNKT-CAR) means an iNKT cell that expresses a chimeric antigen receptor. A dual iNKT-CAR cell (equivalently, iNKT-dCAR) is an iNKT-CAR cell that expresses two distinct chimeric antigen receptor polypeptides with affinity to different target antigens expressed within the same effector cell, wherein each CAR functions independently. The CAR may be expressed from a single or multiple polynucleotide sequences. A tandem iNKT-CAR cell (equivalently, iNKT-tCAR) is an iNKT-CAR cell with a single chimeric antigen polypeptide containing two distinct antigen recognition domains with affinity to different targets, wherein the antigen recognition domains are linked through a peptide linker and share common costimulatory domain(s), and wherein binding of either antigen recognition domain will signal though a common costimulatory domains(s) and signaling domain.

[0292] The term "chimeric antigen receptor T cell" (equivalently, CAR-T) means an T cell that expresses a chimeric antigen receptor.

[0293] The term dual CAR-T (dCAR-T), means a CAR-T cell that expresses cells two distinct chimeric antigen receptor polypeptides with affinity to different target antigen expressed within the same effector cell, wherein each CAR functions independently. The CAR may be expressed from single or multiple polynucleotide sequences.

[0294] The term tandem CAR-T (tCAR-T) means a single chimeric antigen polypeptide containing two distinct antigen recognition domains with affinity to different targets wherein the antigen recognition domain is linked through a peptide linker and share common costimulatory domain(s), wherein the binding of either antigen recognition domain will signal through a common co-stimulatory domains(s) and signaling domain.

[0295] As used herein, a chimeric antigen receptor natural killer (NK) cell (equivalently, NK-CAR) would have a meaning analogous to the definitions of CAR-T and iNKT-CAR.

[0296] As used herein, a chimeric antigen receptor macrophage (equivalently, CAR-macrophage) would have a meaning analogous to the definitions of CAR-T, iNKT-CAR, and NK-CAR.

[0297] As used herein, the term "cytokine release syndrome" refers to a condition that may occur after treatment with some types of immunotherapy, such as monoclonal antibodies and CAR-T or other CAR-bearing immune effector cells. Cytokine release syndrome is caused by a large, rapid release of cytokines into the blood from immune cells affected by the immunotherapy. Symptoms of CRS include fever, fatigue, loss of appetite, muscle and joint pain, nausea, vomiting, diarrhea, rashes, fast breathing, rapid heartbeat, low blood pressure, seizures, headache, confusion, delirium, hallucinations, tremor, and loss of coordination. CRS can manifest along a spectrum of mild to fatal, and can be ranked by severity as follows:

[0298] Grade 1: Mild reaction, infusion interruption not indicated; intervention not indicated

[0299] Grade 2: Therapy or infusion interruption indicated but responds promptly to symptomatic treatment (e.g., antihistamines, NSAIDS, narcotics, IV fluids); prophylactic medications indicated for <=24 hrs

[0300] Grade 3: Prolonged (e.g., not rapidly responsive to symptomatic medication and/or brief interruption of infusion); recurrence of symptoms following initial improvement; hospitalization indicated for clinical sequelae (e.g., renal impairment, pulmonary infiltrates)

[0301] Grade 4: Life-threatening consequences; pressor or ventilatory support indicated

[0302] Grade 5: Death See, e.g., "Common Terminology Criteria for Adverse Events (CTCAE) Version v4.03," National Institutes of Health and National Cancer Institute, Jun. 14, 2010; Lee D W et al., "Current concepts in the diagnosis and management of cytokine release syndrome," Blood 2014 124(2):188-95.

[0303] As used herein, the term "CAR-T associated neuropathy" means neuropathy that arises subsequent to administration of CAR-T therapy to a patient, often after intervening cytokine release syndrome has occurred and subsided. The term is relatively new, mainly because CAR-T therapy is relatively new; see, e.g., Vasthie P and Breitbart WS, "Chimeric antigen receptor T-cell neuropsychiatric toxicity in acute lymphoblastic leukemia," Palliat Support Care. 2017 August; 15(4): 499-503. Accordingly, CAR-T associated neuropathy should be understood at this time to be equivalent to the term "CAR-bearing immune effector cell associated neuropathy," since similar neuropathy could arise from therapy with, e.g., iNKT-CARs or NK-CARs.

[0304] As used herein, a "cytokine" is one of a class of small (.about.5-20 kDa), soluble signaling proteins that are that are synthesized and secreted by certain cells of the immune system at variable, and occasionally locally high, concentrations and by binding to receptors on other cells, send signals to and have an effect on those cells. A "chemokine" is a chemotactic cytokine, i.e., a subspecies of cytokine that is able to induce chemotaxis in nearby responsive cells.

[0305] As used herein, to be "deficient" in a cytokine or protein means to lack sufficient quantity of the cytokine or protein for the cytokine or protein to elicit its normal effect. A cell that is "deficient" in GM-CSF, for example, (a "GM-CSF deficient" cell) could be entirely lacking in GM-CSF, but it also could express such a negligible quantity of GM-CSF that the GM-CSF present could not contribute in any meaningful way to the development or maintenance of cytokine release syndrome.

[0306] The term "deletion" as used herein in reference to the effect of editing on a gene or its protein product, means alteration or loss of part the sequence of DNA encoding the protein so as to reduce or prevent expression of the protein product. The term "suppression" in the same context means to reduce expression of the protein product; and the term "ablation" in the same context means to knock out (KO) or prevent expression of the protein product. Deletion encompasses suppression and ablation.

[0307] As used herein, a "secretable protein" is s protein secreted by a cell which has an effect on other cells. By way of example, secretable proteins include cytokines, chemokines, and transcription factors.

[0308] As used herein, a "selectable marker" refers to a marker that allows distinguishing between different cell types, such as a cell into which a CAR has been successfully inserted (i.e., a gene-edited or modified cell). Selectable markers are well known in the art and materials and methods for their use are readily available. In some embodiments, a selectable marker appropriate in accordance with the present disclosure may be a fluorescent protein gene, such as including, but not limited to, a green fluorescence (GFP) gene or a yellow fluorescent protein (YFP) gene. In some embodiments, a selectable marker may be a splice variant of a CD34 gene, such as a truncated CD34 (tCD34) gene or a truncated EGFR (tEGFR) gene. In some embodiments, a selectable marker described herein, such as GFP, or others known and available in the art, may be inserted alone into a gene as described herein (i.e., without a CAR), or may be inserted as a component of a construct comprising the selectable marker and a CAR.

[0309] As used herein, a "short hairpin RNA" or "small hairpin RNA" (shRNA) is an artificial RNA molecule, often about 80 base pairs in length and with a tight hairpin turn, that can be used to silence target gene expression via processing within the cell into siRNA which in turn knocks down gene expression. ShRNAs can be incorporated into genomic DNA, and provide stable and long-lasting expression.

[0310] As used herein, "transduction" is the process by which foreign DNA is introduced into a cell by a virus or viral vector such as a plasmid, for example by short hairpin RNAs (shRNAs); it often provides long-lasting or permanent silencing of a gene. It may be accomplished by methods known in the art, including electroporation.

[0311] Transfection is the process of deliberately introducing purified nucleic acids into eukaryotic cells, for example small interfering RNAs (siRNAs); it produces transient silencing of a gene by RNA interference with mRNA transcripts. Transduction is the process by which foreign DNA is introduced into a cell by a virus or viral vector such as a plasmid, for example by short hairpin RNAs (shRNAs); it often provides long-lasting or permanent silencing of a gene. Both may be accomplished by methods known in the art, including electroporation.

EXAMPLES

[0312] The invention is further illustrated by the following examples.

Example 1

Method of Blocking Gene Translation by CAR Insertion

[0313] FIG. 1 shows the deletion of a cytokine gene by using Cas9/CRISPR to target a locus in a cytokine gene, then use homology-directed repair to insert the CAS construct. Optionally, the CAS construct would contain a marker, such as a selectable marker as described herein. One challenge with this concept is that is hard to select and sort out the cells have been edited from those that still express the cytokine/chemokine. One way to overcome this is to insert the CAR construct containing a marker, into gene that has been deleted. It has previously been demonstrated that inserting CAR19 into the TRAC gene allows the selection of TRAC-negative, CAR-positive cells. This would allow sorting of cells that have both expression of the car and have the cytokine deleted. Another alternative would be to express a shRNA from the CAR construct that would degrade the RNA encoding for the cytokine without altering the genome. A marker on the CAR construct (such as the truncated CD34 marker) could be used to select cells that downregulate the cytokine and express the CAR, i.e., CAR+=Cytokine negative.

[0314] As shown in FIG. 2, CAR-bearing immune effector cells (e.g., CAR-T) would be activated for two days prior to gene editing to delete the target cytokine gene and transduction of CAR.

Example 2

General Method of Making Genome-Edited CAR-Bearing Immune Effector Cells

[0315] Further details regarding the manner of making CAR-bearing immune effector cells are known in the art, e.g., as disclosed in WO2018027036A1.

[0316] The following general steps may be taken to provide CAR-bearing immune effector cells. As those of skill in the art will recognize, certain of the steps may be conducted sequentially or out of the order listed below, though perhaps leading to different efficiency.

[0317] Step 1. Cells are harvested, isolated, and purified, for example using magnetic selection with a labelled antibody-coated magnetic beads that bind to a cell-specific protein (available from, e.g., Miltenyi Biotec). For T cells, anti-CD3/CD28 beads could be used. Other purification techniques are known in the art and could be used.

[0318] Step 3. Cells are thereafter activated. There are several ways to activate immune effector cells. For example, T cells may be activated using antiCD3/CD28 beads for two days prior to bead removal. Alternatively, an antibody could be used.

[0319] Step 4. The antigen that is the target of the CAR may be deleted from the cell surface or its expression suppressed to prevent subsequent fratricide. Target deletion may be accomplished by electroporation with Cas9 mRNA and gRNA against the target(s). Other techniques, however, could be used to suppress expression of the target. These include other genome editing techniques such as TALENs, ZFNs, RNA interference, and eliciting of internal binding of the antigen to prevent cell surface expression. Deletion of the target may not be required in every circumstance. Examples of gRNAs that may be used include those shown in Tables 8-10, as well as others known in the art.

TABLE-US-00008 TABLE 8 Guide RNA sequences for use in removing surface antigens on immune effector cells Target gene gRNA sequence CD7 5'_2'OMe(A(ps)U(ps)C(ps))ACGGAGGUCAAUGUCUAGUUUUAGAGCUAGA AAUAGCAAGUUAAAAUAAGGCUAGUCCGUUAUCAACUUGAAAAAGUG GCACCGAGUCGGUGC2'OMe(U(ps)U(ps)U(ps)U_3' (SEQ ID NO: 40) CD7g10 5'_2'OMe(G(ps)U(ps)A(ps))GACAUUGACCUCCGUGAGUUUUAGAGCUAGA AAUAGCAAGUUAAAAUAAGGCUAGUCCGUUAUCAACUUGAAAAAGUG GCACCGAGUCGGUGC2'OMe(U(ps)U(ps)U(ps)U_3' (SEQ ID NO: 41) CD7g4 5'_2'OMe(A(ps)U(ps)C(ps))ACGGAGGUCAAUGUCUAGUUUUAGAGCUAGA AAUAGCAAGUUAAAAUAAGGCUAGUCCGUUAUCAACUUGAAAAAGUG GCACCGAGUCGGUGC2'OMe(U(ps)U(ps)U(ps)U_3' (SEQ ID NO: 42) TRACg 5'_2'OMe(G(ps)A(ps)G(ps))AAUCAAAAUCGGUGAAUGUUUUAGAGCUAGA AAUAGCAAGUUAAAAUAAGGCUAGUCCGUUAUCAACUUGAAAAAGUG GCACCGAGUCGGUGC2'OMe(U(ps)U(ps)U(ps)U_3' (SEQ ID NO: 43) CS1 5'_2'OMe(G(ps)A(ps)C(ps))CAAUCUGACAUGCUGCAGUUUUAGAGCUAGA AAUAGCAAGUUAAAAUAAGGCUAGUCCGUUAUCAACUUGAAAAAGUG GCACCGAGUCGGUGC2'OMe(U(ps)U(ps)U(ps)U_3' (SEQ ID NO: 44) CD2 5'_2'OMe(A(ps)C(ps)A(ps))GCUGACAGGCUCGACACGUUUUAGAGCUAGA AAUAGCAAGUUAAAAUAAGGCUAGUCCGUUAUCAACUUGAAAAAGUG GCACCGAGUCGGUGC2'OMe(U(ps)U(ps)U(ps)U_3' (SEQ ID NO: 45) CD2g 5'_2'OMe(G(ps)A(ps)G(ps))AAUCAAAAUCGGUGAAUGUUUUAGAGCUAGA AAUAGCAAGUUAAAAUAAGGCUAGUCCGUUAUCAACUUGAAAAAGUG GCACCGAGUCGGUGC2'OMe(U(ps)U(ps)U(ps)U 3' (SEQ ID NO: 46) CD3 g 5'_2'OMe(A(ps)G(ps)G(ps))GCAUGUCAAUAUUACUGGUUUUAGAGCUAGA AAUAGCAAGUUAAAAUAAGGCUAGUCCGUUAUCAACUUGAAAAAGUG GCACCGAGUCGGUGC2'OMe(U(ps)U(ps)U(ps)U 3' (SEQ ID NO: 47) CD5 5'_2'OMe(C(ps)G(ps)U(ps))UCCAACUCGAAGUGCCAGUUUUAGAGCUAGA AAUAGCAAGUUAAAAUAAGGCUAGUCCGUUAUCAACUUGAAAAAGUG GCACCGAGUCGGUGC2'OMe(U(ps)U(ps)U(ps))U_3' (SEQ ID NO: 48) CD5g 5'_2'OMe(C(ps)G(ps)U(ps))uCCAACUCGAAGUGCCAGUUUUAGAGCUAGA AAUAGCAAGUUAAAAUAAGGCUAGUCCGUUAUCAACUUGAAAAAGUG GCACCGAGUCGGUGC2'OMe(U(ps)U(ps)U(ps)U_3' (SEQ ID NO: 49) RNA; (ps) indicate phosphorothioate. Underlined bases denote target sequence.

[0320] Step 5. Cells may then be transduced with a CAR targeted to (i.e., that recognizes) one or more antigen or protein targets, for example with a lentivirus containing a CAR construct. Any other suitable method of transduction/transfection may be used, for example transfection using DNA-integrating viral or non-viral vectors containing transposable elements, or transient expressing of non-DNA integrating polynucleotides, such as mRNA, or insertion of CAR polynucleotide into site of nuclease activity using homologous or non-homologous recombination.

[0321] Step 6. CAR-bearing immune effector cells are then cultured to expand their population.

Example 3

Method of Making Genome-Edited Tandem CAR-Bearing Immune Effector Cells

[0322] In a variation of the protocol in the example above, a tCAR cell recognizing two antigens can be made. In Step 4, the two antigens can be deleted from the cell surface, or suppressed as described above, but electroporation with gRNA for each of the two targets and Cas9 mRNA. In Step 5, cells are then transduced with a CAR that recognizes two targets.

Example 4

Method of Making Genome-Edited Dual CAR-Bearing Immune Effector Cells

[0323] In a variation of the protocol in the example above, a dCAR cell targeting two antigens can be made. This variation would contain two separate CARs, each recognizing a different antigen.

Example 5

Method of Making and Testing a Genome-Edited CAR-T Cell with Suppressed Expression of Cytokine or Chemokine

[0324] The following steps may be taken to provide a genome-edited CAR-T cell with suppressed expression and/or secretion of a specific cytokine or chemokine. This example describes the making of a CD19 targeting CAR-T which is deficient in expression of GM-CSF. As those of skill in the art will recognize, certain of the steps may be conducted sequentially or out of the order listed below, though perhaps leading to different efficiency.

[0325] Tumor is injected into SCID-Beige mice (3e6 Raji containing Luciferase) if performing in vivo CRS experiment. This should be completed 3 weeks prior to infusion of CAR-T into mice.

[0326] T Cell Activation (Day 0).

[0327] T cells are purified via leukapheresis chamber using a Miltenyi human PanT isolation kit, then resuspended in media. Cells are counted and the number of human T cell activation CD3/CD28 beads required to obtain 3:1 bead:cell ratio determined. Beads are washed 2.times. with T cell media, then cells diluted at 1.256 cells/mL in hXcyte media. Human T cell activation CD3/CD28 beads are added. Into each well of a 6-well plate are aliquoted 4 mL/well of 1.256 cell/mL solution. Cells are incubated at 37.degree. C.

[0328] CRISPR (Day 2).

[0329] Target deletion may be accomplished by electroporating with Cas9 mRNA and gRNA against the target(s). Other techniques, however, could be used to suppress expression of the target. These include other genome editing techniques such as TALENs, RNA interference, and eliciting of internal binding of the antigen to prevent cell surface expression. Examples of gRNAs that may be used include those shown in Tables 8-10, as well as others known in the art.

TABLE-US-00009 Nucleofection Sample ID gRNA#1 Cas9 Buffer P3 20 .mu.g gGM-CSF 15 .mu.g Cas9 mRNA 100 .mu.l

TABLE-US-00010 Table 9 GUIDE RNA sequences for use in reducing CRS Target gene gRNA sequence GM-CSF 5'_2'OMe(U(ps)A(ps)C(ps))UCAGGUUCAGGAGACGC GUUUUAGAGCUAGAAAUAGCAAGUUAAAAUAAGGCUAGUCCG UUAUCAACUUGAAAAAGUGGCACCGAGUCGGUGC2'OMe (U(ps)U(ps)U(ps)U_3' (SEQ ID NO: 50) RNA; (ps) indicate phosphorothioate. Underlined bases denote target sequence.

TABLE-US-00011 TABLE 10 Additional guide RNA sequences for use in reducing the incidence of CRS Target Gene SEQ Symbol Guide RNA Sequence ID NO: Location Gene ID No. A2M GACAAAUCAAUCUACAAACC 56 chr12 ENST00000318602.11 A2M GGUCCGCUUCUUAAAUUCUU 57 chr12 ENST00000318602.11 A2M UCCUCAUUGGAUGAAGACUU 58 chr12 ENST00000318602.11 ACKR1 AACUGAGAACUCAAGUCAGC 59 chr1 ENST00000368122.2 ACKR1 GAAGGAAUCAUUCACACCAU 60 chr1 ENST00000368122.2 ACKR1 ACACUGGUGAGGAUGAAGAA 61 chr1 ENST00000368122.2 ACKR2 UCGGCAUCCUCAGUGGCGAG 62 chr3 ENST00000422265.5 ACKR2 GCAUGAAGGCCACUUCAUCC 63 chr3 ENST00000422265.5 ACKR2 AAAUCAGGCUAUAGAAGACU 64 chr3 ENST00000422265.5 ACKR3 UAGAGCAGGACGCUUUUGUU 65 chr2 ENST00000272928.3 ACKR3 CGGCAUGAUUGCCAACUCCG 66 chr2 ENST00000272928.3 ACKR3 CCCACAGGUCGGCAAUGGCC 67 chr2 ENST00000272928.3 ACVR1 UCUUUCCCUGCUCAUAAACC 68 chr2 ENST00000263640.7 ACVR1 UCCUCACUGAGCAUCAACGA 69 chr2 ENST00000263640.7 ACVR1 CUCUACAUGUGUGUGUGUGA 70 chr2 ENST00000263640.7 ACVR2B CUACAACGCCAACUGGGAGC 71 chr3 ENST00000352511.4 ACVR2B GCCAGAGCUGUUGCGCCAGG 72 chr3 ENST00000352511.4 ACVR2B AUGACUUCAACUGCUACGAU 73 chr3 ENST00000352511.4 ACVRL1 AGACCCUGUGAAGCCGUCUC 74 chr12 ENST00000388922.8 ACVRL1 GGCCUACCUGCCGGGGGGCC 75 chr12 ENST00000388922.8 ACVRL1 GGGGCUGCGGGAACUUGCAC 76 chr12 ENST00000388922.8 ADIPOQ GGGCUCAGGAUGCUGUUGCU 77 chr3 ENST00000320741.6 ADIPOQ CGUGGUUUCCUGGUCAUGAC 78 chr3 ENST00000320741.6 ADIPOQ GGGGGCCUGCACAGGUUGGA 79 chr3 ENST00000320741.6 AGER ACGGACUCGGUAGUUGGACU 80 chr6 ENST00000375076.8 AGER CUGUCGGGAUCCAGGAUGAG 81 chr6 ENST00000375076.8 AGER UCCCCAGGGAGGAGGCCCCU 82 chr6 ENST00000375076.8 AGRN CGGGGAAUGCUGUGCGGCUU 83 chr1 ENST00000379370.6 AGRN GAAGAGCCCGUGCCCCAGCG 84 chr1 ENST00000379370.6 AGRN GCAUUCGUUGCUGUAGGUGG 85 chr1 ENST00000379370.6 ##STR00001## ##STR00002## 86 ##STR00003## ##STR00004## ##STR00005## ##STR00006## 87 ##STR00007## ##STR00008## ##STR00009## ##STR00010## 88 ##STR00011## ##STR00012## ##STR00013## ##STR00014## 89 ##STR00015## ##STR00016## AIMP1 AACCAAUUCGAAGAUCCAGA 90 chr4 ENST00000358008.7 AIMP1 UAUGUGGAAGAAGUAGAUGU 91 chr4 ENST00000358008.7 AIMP1 CAAGAGGAACAUGAUUCACC 92 chr4 ENST00000358008.7 AREG GGUCCAAUCCAGCAGCAUAA 93 chr4 ENST00000395748.7 AREG CCACAGUGCUGAUGGAUUUG 94 chr4 ENST00000395748.7 AREG AGAAGGCAUUUCACUCACAG 95 chr4 ENST00000395748.7 BCL6 CUGUAAAGAUGCUAUAGAAC 96 chr3 ENST00000406870.6 BCL6 CACUAAGGUUGCAUUUCAAC 97 chr3 ENST00000406870.6 BCL6 GAUCUAGAUUGAUCACACUA 98 chr3 ENST00000406870.6 BCL6 AAUCCCUCAGGGUUGAUCUC 99 chr3 ENST00000406870.6 BMP1 CAGCGGCAGGCGGGCCACGC 100 chr8 ENST00000306385.9 BMP1 GGCCGACUACACCUAUGACC 101 chr8 ENST00000306385.9 BMP1 GGCGCUCACCCGCCUUGCAG 102 chr8 ENST00000306385.9 BMP10 GAAACUCAUCCUUCAUGCUC 103 chr2 ENST00000295379.1 BMP10 AGGGACAUAUCUUCUUCCAG 104 chr2 ENST00000295379.1 BMP10 CAGAAACCAAGUAAGCUGCC 105 chr2 ENST00000295379.1 BMP15 CGUGCUUUUCAUGGAACACA 106 chrX ENST00000252677.3 BMP15 CCCUACUUUGCCCCUGAUUG 107 chrX ENST00000252677.3 BMP15 AGUGAAUGCCCUAGGAGCCG 108 chrX ENST00000252677.3 BMP2 CGCAGGUCGACCAUGGUGGC 109 chr20 ENST00000378827.4 BMP2 GGGCCGCAGGAAGUUCGCGG 110 chr20 ENST00000378827.4 BMP2 GCCGCAACUCGAACUCGCUC 111 chr20 ENST00000378827.4 BMP3 AGGCUGCUCUUUCUGUGGCU 112 chr4 ENST00000282701.2 BMP3 GGCACAGCUUUGCGGAGCUC 113 chr4 ENST00000282701.2 BMP3 CGAGCUGCAGCCGCAAGACA 114 chr4 ENST00000282701.2 BMP4 UUCGUGGUGGAAGCUCCUCA 115 chr14 ENST00000245451.8 BMP4 GAAGAGCAGAUCCACAGCAC 116 chr14 ENST00000245451.8 BMP4 CACUCUUGCUAGGCUGCGGG 117 chr14 ENST00000245451.8 BMP5 ACUGAGUACUCCGACUCUUC 118 chr6 ENST00000370830.3 BMP5 AGACCCAGACCAUUUUCACC 119 chr6 ENST00000370830.3 BMP5 CGAAAGACGGGAAAUACAAA 120 chr6 ENST00000370830.3 BMP6 GAUGCAGAAGGAGAUCUUGU 121 chr6 ENST00000283147.6 BMP6 GGCUGUUGGAGGCCGUGCAG 122 chr6 ENST00000283147.6 BMP6 CCUCGCGGAGAGCCCCCUCC 123 chr6 ENST00000283147.6 BMP7 UCUCAUUGUCGAAGCGUUCC 124 chr20 ENST00000395863.7 BMP7 GCCGUGACAGCUUCCCCUUC 125 chr20 ENST00000395863.7 BMP7 UCUUCCAGUGGAACAUGACA 126 chr20 ENST00000395863.7 BMP8A CCAGAAGCCAGAGCGGUCCG 127 chr1 ENST00000331593.5 BMP8A UGGCGGUGCUCGGGCUACCC 128 chr1 ENST00000331593.5 BMP8A UGGCGGUGCUCGGGCUACCC 129 chr1 ENST00000331593.5 BMP8B CGGUGCUCGGGCUGCCUGGG 130 chr1 ENST00000372827.7 BMP8B CCCAGGAGCCAGAGCGGGCC 131 chr1 ENST00000372827.7 BMP8B CCCAGGAGCCAGAGCGGGCC 132 chr1 ENST00000372827.7 BMPR2 CACUUGCAGCUGAUUGGCCG 133 chr2 ENST00000374580.8 BMPR2 UUUCGUUGAUAAAAUUCUGA 134 chr2 ENST00000374580.8 BMPR2 CUCAUCUCCAACUAUAAAGC 135 chr2 ENST00000374580.8 C10orf99 GGAAAGGACUAGAAGCCUCA 136 chr10 ENST00000372126.3 C10orf99 CCUACCUUCUGUGGAGAAGA 137 chr10 ENST00000372126.3 C10orf99 CUCUGAUCAGGAUUUGUUGG 138 chr10 ENST00000372126.3 C1QTNF4 CCAUCUCCGACGUGCCCUCC 139 chr11 ENST00000302514.3 C1QTNF4 CAGCUCAGAGGAUCCCGGGC 140 chr11 ENST00000302514.3 C1QTNF4 CCCAGCAGGCCCAGCAGAAG 141 chr11 ENST00000302514.3 C5* UCCAGCACCGUCACUCCAGA 142 chr9 ENST00000223642.2 C5* ACACGUGUUACACUUUUGCU 143 chr9 ENST00000223642.2 C5* GAUUCGCUUGACCAGUUGGU 144 chr9 ENST00000223642.2 CCL1* AGAAACGUGGUCAGCCACUC 145 chr17 ENST00000225842.3 CCL1* CUCUUGCUGUCCACAUCUUC 146 chr17 ENST00000225842.3 CCL1* GCAGAUCAUCACCACAGCCC 147 chr17 ENST00000225842.3 CCL11 AGGUCUCCGCAGCACUUCUG 148 chr17 ENST00000305869.3 CCL11 CUGGCCCAGCGAGCCCCUGG 149 chr17 ENST00000305869.3 CCL11 UAACCACCUCCAGAGCUACU 150 chr17 ENST00000305869.3 CCL13* AUGUGAAGCAGCAAGUAGAU 151 chr17 ENST00000225844.6 CCL13* CUUCUGGGGACACCUGCUGG 152 chr17 ENST00000225844.6 CCL13* AACUUUGGAUUGGGGAAUGU 153 chr17 ENST00000225844.6 CCL14 CAGGAGUGAGGUUGGGGCUC 154 chr17 ENST00000618404.4 CCL14 GGCAUUGCACUCACGUGAGG 155 chr17 ENST00000618404.4 CCL14 CCACAGCAUGAAGAUCUCCG 156 chr17 ENST00000618404.4 CCL15* UCCCAGAGCUUGAGUUACCA 157 chr17 ENST00000617897.1 CCL15* CACCAUUUGUGAACUGGGCC 158 chr17 ENST00000617897.1 CCL15* CACCAUUUGUGAACUGGGCC 159 chr17 ENST00000617897.1 CCL16 GGACGUGCUUACAUGAUUGC 160 chr17 ENST00000611905.1 CCL16 GUUGCCAAGGAGACUAGUGG 161 chr17 ENST00000611905.1 CCL16 UCCUUCAGAAGUUCCUGAGU 162 chr17 ENST00000611905.1 CCL17 GCUCCUCUCCCUGCAGCUCG 163 chr16 ENST00000219244.8 CCL17 UGGCUCCCUUGAAGUACUCC 164 chr16 ENST00000219244.8 CCL17 UGGAGCAGUCCUCAGAUGUC 165 chr16 ENST00000219244.8 CCL18 GAGGCAGCAGAGCUCUUUGU 166 chr17 ENST00000616054.1 CCL18 UGGCUUGGGGCACUGGGGGC 167 chr17 ENST00000616054.1 CCL18 CCAUCCUCCCUCCCGAGGGG 168 chr17 ENST00000616054.1 CCL19 CCCACAACUCACACUACAGC 169 chr9 ENST00000311925.6 CCL19 AAGUUCCUCACGAUGUACCC 170 chr9 ENST00000311925.6 CCL19 CAUUGGUGCCACUCAGAGUU 171 chr9 ENST00000311925.6 CCL2 GUUAUAACAGCAGGUGACUG 172 chr17 ENST00000225831.4 CCL2 UUCUUUGGGACACUUGCUGC 173 chr17 ENST00000225831.4 CCL2 GGCUUGUCCCUUGCUCCACA 174 chr17 ENST00000225831.4 CCL20 CAAACUCUUGGUACAGCACA 175 chr2 ENST00000358813.4 CCL20 CACCUCUGCGGCGAAUCAGA 176 chr2 ENST00000358813.4 CCL20 CAGUUGAGCUCAAGGCUAAA 177 chr2 ENST00000358813.4 CCL21 CCCUGCAGGCAGUGAUGGAG 178 chr9 ENST00000259607.6 CCL21 CCUCCCUGCCUUGGUACCUU 179 chr9 ENST00000259607.6 CCL21 GGCUCUGAGCCUCCUUAUCC 180 chr9 ENST00000259607.6 CCL22 ACCCCUCCCCUAGGCCCCUA 181 chr16 ENST00000219235.4 CCL22 GACGGUAACGGACGUAAUCA 182 chr16 ENST00000219235.4 CCL22 AGGCCUCGGGCAGGAGUCUG 183 chr16 ENST00000219235.4 CCL23* UCGUUUCAAAGUAACUCUCC 184 chr17 ENST00000615050.1 CCL23* AGCAGUCAGCACUAGUAGCA 185 chr17 ENST00000615050.1 CCL23* GUGCUCUGGAGGAGAAAGAU 186 chr17 ENST00000615050.1 CCL24 CCUCAAGGCAGGAGUGAUGU 187 chr7 ENST00000222902.6 CCL24 GAGAAUUCCUGAGAACCGAG 188 chr7 ENST00000222902.6 CCL24 CUCUCCUCUUCUAGGCUCUG 189 chr7 ENST00000222902.6 CCL25 UGUGGUUGCAGGUGUCUUUG 190 chr19 ENST00000390669.7 CCL25 GGGCUGUGCUCCGGCGCGCC 191 chr19 ENST00000390669.7 CCL25 GGCCCCACUCACAUCGCAGC 192 chr19 ENST00000390669.7 CCL26 CCAUCCUGUUGCAUGACUGA 193 chr7 ENST00000005180.8 CCL26 CCAGUAACAGCUGCUCCCAG 194 chr7 ENST00000005180.8 CCL26 GUAUUGGAAGCAGCAGGUCU 195 chr7 ENST00000005180.8 CCL27 GAGCUCACACGAAAGCCUGG 196 chr9 ENST00000259631.4 CCL27 ACUGAGGAAGGUCAUCCAGG 197 chr9 ENST00000259631.4 CCL27 AGGCAGUGCUGGGUGGCAGU 198 chr9 ENST00000259631.4 CCL28 AAUCCUUCCAGCACAGAUUU 199 chr5 ENST00000361115.4 CCL28 GUGCCCCCACUCACCUUCUG 200 chr5 ENST00000361115.4 CCL28 CAGGCAGGAAUGCAGCAGAG 201 chr5 ENST00000361115.4 CCL3 GCCACAAGAAAAGAUUGAUG 202 chr17 ENST00000613922.1 CCL3 ACUCACGUGAUGCAGAGAAC 203 chr17 ENST00000613922.1 CCL3 UCACCUGCUCAGAAUCAUGC 204 chr17 ENST00000613922.1 CCL4* UGAGAGCGCUGGAGAGCAGA 205 chr17 ENST00000615863.1 CCL4* UGAGAGCGCUGGAGAGCAGA 206 chr17 ENST00000615863.1 CCL4* UGAGAGCGCUGGAGAGCAGA 207 chr17 ENST00000615863.1 CCL5 GACUCACACGACUGCUGGGU 208 chr17 ENST00000603197.5 CCL5 UGAUGUGGGCACGGGGCAGU 209 chr17 ENST00000603197.5 CCL5 CUUUCCUCUUCCAGAUUCCU 210 chr17 ENST00000603197.5 CCL7 AUUGAUAAAUCUGUAGCAGC 211 chr17 ENST00000378569.2 CCL7 CCACAUACAUUACAGCUUCC 212 chr17 ENST00000378569.2 CCL7 CUAGUCCUAUUCCCUGCCCA 213 chr17 ENST00000378569.2 CCL8* AAAGCAGCAGGUGAUUGGAA 214 chr17 ENST00000394620.1 CCL8* CACCAACAUCCAAUGUCCCA 215 chr17 ENST00000394620.1 CCL8* CCCCCAUUCAAAAGUUCUGA 216 chr17 ENST00000394620.1 CCR1 CCUGGUUGGAAACAUCCUGG 217 chr3 ENST00000296140.3 CCR1 AGGCCCUCUCGUUCACCUUC 218 chr3 ENST00000296140.3 CCR1 UCAUAGUCCUCUGUGGUGUU 219 chr3 ENST00000296140.3 CCR2 GAUAAACCGAGAACGAGAUG 220 chr3 ENST00000445132.2 CCR2 ACCUUUUUUGAUUAUGAUUA 221 chr3 ENST00000445132.2 CCR2 GUAGAGCGGAGGCAGGAGUU 222 chr3 ENST00000445132.2 CCR3 CUAGAUACAGUUGAGACCUU 223 chr3 ENST00000357422.2 CCR3 UAUCAGCUUUUUCACAGAGC 224 chr3 ENST00000357422.2 CCR3 GGUGUUCACUGUGGGCCUCU 225 chr3 ENST00000357422.2 CCR5 UUUUGCAGUUUAUCAGGAUG 226 chr3 ENST00000292303.4 CCR5 AAAACAGGUCAGAGAUGGCC 227 chr3 ENST00000292303.4 CCR5 UGUAUUUCCAAAGUCCCACU 228 chr3 ENST00000292303.4 CCR6 UUGUUCUUACUCUCCCAUUC 229 chr6 ENST00000341935.9 CCR6 GCCUUUUAGCAACUUGCACG 230 chr6 ENST00000341935.9 CCR6 CCGGUACAUCGCCAUUGUAC 231 chr6 ENST00000341935.9 CCR7 GGCCGCGCUGUAGGCCCAGA 232 chr17 ENST00000246657.2 CCR7 GAGCAGGUAGGUAUCGGUCA 233 chr17 ENST00000246657.2 CCR7 UAGGCCCACGAAACAAAUGA 234 chr17 ENST00000246657.2 CD109 UCCGGGCCUGAUGAUCCCUG 235 chr6 ENST00000287097.5 CD109 GCCUUCACAGUCACCUGUGA 236 chr6 ENST00000287097.5 CD109 CAAAGACUCCUUCUGCUUCC 237 chr6 ENST00000287097.5 CD27** CCUUCACGAGGAAUGUUCCU 238 chr12 ENST00000266557.3 CD27** UCCUUCACGAGGAAUGUUCC 239 chr12 ENST00000266557.3 CD27** GCUGGUCACAGUCCUUCACG 240 chr12 ENST00000266557.3 CD27** ACUGAGCAGCCUUUCUAUGC 241 chr12 ENST00000266557.3 CD28*** CACCAAAAUCUUGUUUCCUG 242 ch2 ENST00000458610.6 CD28*** UCACCAAAAUCUUGUUUCCU 243 ch2 ENST00000458610.6 CD28*** UUGUCGUACGCUACAAGCAU 244 ch2 ENST00000458610.6 CD28*** AUUGUCGUACGCUACAAGCA 245 ch2 ENST00000458610.6 CD36 CAAGAAAAAUGGGCUGUGAC 246 chr7 ENST00000309881.11 CD36 GGUGCUGUCCUGGCUGUGUU 247 chr7 ENST00000309881.11 CD36 UAUCCAGAAGACAAUUAAAA 248 chr7 ENST00000309881.11 CD4** AGUGCAAUGUAGGAGUCCAA 249 chr12 ENST00000011653.8 CD4** CUGGAGCUCCAGCUGAGACA 250 chr12 ENST00000011653.8 CD4** UUUUGAACUCCACCUUCUUC 251 chr12 ENST00000011653.8 CD40LG** CAAAAUAGAUAGAAGAUGAA 252 chrX ENST00000370629.6 CD40LG** ACGAUACAGAGAUGCAACAC 253 chrX ENST00000370629.6 CD40LG** CCAGUUUGAAGGCUUUGUGA 254 chrX ENST00000370629.6 CD70 AGCGCUGGAUGCACACCACG 255 chr19 ENST00000245903.3 CD70 AGCCCGCAGGACGCACCCAU 256 chr19 ENST00000245903.3 CD70 CGCCGCGGCGAUGCCGGAGG 257 chr19 ENST00000245903.3 CD74 UGCUCACACAUACCUCUCCG 258 chr5 ENST00000009530.11 CD74 UGUUGGAGAUAAGGUCGCGC 259 chr5 ENST00000009530.11 CD74 AGAUGCACAGGAGGAGAAGC 260 chr5 ENST00000009530.11 CD8A** CCGGAACUGGCUCGGCCUGG 261 ch2 ENST00000409511.6 CD8A** CACCCGGAACUGGCUCGGCC 262 ch2 ENST00000409511.6 CD8A** GGCGACACCCGGAACUGGCU 263 ch2 ENST00000409511.6 CD8A** CGCCAGGCCGAGCCAGUUCC 264 ch2 ENST00000409511.6 CER1 GGCACUGCGACAAACAGAUC 265 chr9 ENST00000380911.3 CER1 AAAGAGAACUCUGAUUCUGG 266 chr9 ENST00000380911.3 CER1 CUGCUGGUACUCCUGCCUCU 267 chr9 ENST00000380911.3 CHRD GCCGGCGGGGCCGGGAGGCU 268 chr3 ENST00000204604.5 CHRD UCCCGGCCGGCCCGCGGCGC 269 chr3 ENST00000204604.5 CHRD CUGCCCGUUCGGGGAGCGGC 270 chr3 ENST00000204604.5 CKLF GUGAUAACAAUAUAUGGUUC 271 chr16 ENST00000264001.8 CKLF GACUUGAUCGAUUAAUGAAG 272 chr16 ENST00000264001.8 CKLF GUAGGAAAAAGUAAAAUUUA 273 chr16 ENST00000264001.8 CLCF1 CAUAGGUCCCAGCCAAGCUG 274 chr11 ENST00000312438.7 CLCF1 CAUAGGUUUUCUGGAUGGAG 275 chr11 ENST00000312438.7 CLCF1 GGUGCCAGAGCACCGUGCAC 276 chr11 ENST00000312438.7 CMTM1 GACUCAGGUUUGGCGUGUUC 277 chr16 ENST00000379500.6 CMTM1 UACGCUGCCGCUACUUGCCA 278 chr16 ENST00000379500.6 CMTM1 UGCGGGGUGCUUCCGGGGUG 279 chr16 ENST00000379500.6 CMTM2 CGAGUCAGUCAUGGCACCUA 280 chr16 ENST00000268595.2 CMTM2 UCCACCCGGGGCCAAACCCG 281 chr16 ENST00000268595.2 CMTM2 AAAGGCGGUGCAGGACCAUA 282 chr16 ENST00000268595.2 CMTM3 CCGGACCCCGAGCCUGCCGG 283 chr16 ENST00000361909.8 CMTM3 GGAAAGCCCGCGCCGGCAGC 284 chr16 ENST00000361909.8 CMTM3 UCCCGCCGCACUCACCGACU 285 chr16 ENST00000361909.8 CMTM4 CCGCCCGGCACCUACCACUU 286 chr16 ENST00000394106.6 CMTM4 GGUAGUCGGGGUCGCAGCGC 287 chr16 ENST00000394106.6 CMTM4 GCUGCUGGCGCCCGAGAUCA 288 chr16 ENST00000394106.6 CMTM5 GCUCAGUGCUCGAGAUCGCC 289 chr14 ENST00000359320.7 CMTM5 CCAGGGCUUCGCGGUGGACA 290 chr14 ENST00000359320.7 CMTM5 UUACCAGCUCGGUUUCCAGC 291 chr14 ENST00000359320.7 CMTM6 UUGAGAACGCGCCGGAGCAA 292 chr3 ENST00000205636.3 CMTM6 CGCUCCGGGGGCCUCUGGCG 293 chr3 ENST00000205636.3

CMTM6 CGGCCCGAGGCGAUGGAGAA 294 chr3 ENST00000205636.3 CMTM7 GGAGCUCCGCACACAGAUGA 295 chr3 ENST00000334983.9 CMTM7 AAUGAUCCUCGCCUUUUACC 296 chr3 ENST00000334983.9 CMTM7 CGACAGGGGCCAGCUGAUAC 297 chr3 ENST00000334983.9 CMTM8 GUGUGCGAGCGGGCGCGCUG 298 chr3 ENST00000307526.3 CMTM8 CAGCAGCUUCGCCUACGACC 299 chr3 ENST00000307526.3 CMTM8 CCCGUCGGCACUCACGAUCU 300 chr3 ENST00000307526.3 CNTF AUCAACCUGGACUCUGCGGA 301 chr11 ENST00000361987.5 CNTF GGAAGGUACGAUAAGCUUGA 302 chr11 ENST00000361987.5 CNTF GUGCAUUUUACCCCAACCGA 303 chr11 ENST00000361987.5 CNTFR CCAGCUGAGAGCCGUUGAGC 304 chr9 ENST00000351266.8 CNTFR GGGAUGCUGCGGUGACGUGG 305 chr9 ENST00000351266.8 CNTFR CAGGCGCUCGUACUGCACAU 306 chr9 ENST00000351266.8 COPS5 UAGUCCAGGGCUUCGCCGCC 307 chr8 ENST00000357849.8 COPS5 CUGAGCUUCCUGCAUGUUGU 308 chr8 ENST00000357849.8 COPS5 CCUCGGCGAUGGCGGCGUCC 309 chr8 ENST00000357849.8 CRLF1 CCAGCGUGAGUACAUCGGAG 310 chr19 ENST00000392386.7 CRLF1 CAUAGGGCGUAAAGAGAGCC 311 chr19 ENST00000392386.7 CRLF1 ACUCCUCACAUGUGUUGUCC 312 chr19 ENST00000392386.7 CSF1* GCCUUCUUAAGGUAGCACAC 313 chr1 ENST00000329608.10 CSF1* GGUGUUAUCUCUGAAGCGCA 314 chr1 ENST00000329608.10 CSF1* GUCAUGCUCUUCAUAAUCCU 315 chr1 ENST00000329608.10 CSF1R CACCUUUCUGCACUUUCAGC 316 chr5 ENST00000286301.7 CSF1R CAAUGCAGUGCCCUGAUGGG 317 chr5 ENST00000286301.7 CSF1R CCAGGGCGAGAAGGAGUAGU 318 chr5 ENST00000286301.7 CSF2* CCACAGUGCCCAAGAGCAGC 319 chr5 ENST00000296871.3 CSF2* CAGGGCUGCGUGCUGGGGCU 320 chr5 ENST00000296871.3 CSF2* UAGAGACACUGCUGCUGAGA 321 chr5 ENST00000296871.3 CSF3 UGUGCCACAGCAGCAGCUGC 322 chr17 ENST00000225474.6 CSF3 GAAGCUCUGGGGCAGGGAGC 323 chr17 ENST00000225474.6 CSF3 GGGCGAUGGCGCAGCGCUCC 324 chr17 ENST00000225474.6 CSF3R GCAAUAGCAACAAGACCUGG 325 chr1 ENST00000361632.8 CSF3R AUAGCCCUGAGGCCAUGGAU 326 chr1 ENST00000361632.8 CSF3R GCAUGGAGUCUGGUCAGAGC 327 chr1 ENST00000361632.8 CTF1 UCUCCGCAGGUGCAGCUCCA 328 chr16 ENST00000279804.2 CTF1 CCGGCCACCGGCAGCCGCGG 329 chr16 ENST00000279804.2 CTF1 AGCCGCAGCCGCUCGUGCAC 330 chr16 ENST00000279804.2 CX3CL1 GUGCCGACCCGAAGGAGCAA 331 chr16 ENST00000006053.6 CX3CL1 CUUCGAGAAGCAGAUCGGCG 332 chr16 ENST00000006053.6 CX3CL1 CGCCUGUGGCUUCGGGCUCC 333 chr16 ENST00000006053.6 CX3CR1** CUACCAACAAAUUUCCCACC 334 chr3 ENST00000399220.2 CX3CR1** UUGGGGACAUCGUGGUCUUU 335 chr3 ENST00000399220.2 CX3CR1** AAGUUUUCUGUCACUGAUUC 336 chr3 ENST00000399220.2 CXCL1 GGAGAGAGCAGCGCGGGCCA 337 chr4 ENST00000395761.3 CXCL1 CUGGCCGGCGCGCAGCAGGU 338 chr4 ENST00000395761.3 CXCL1 GUGCCUACCCCAGCCGCGUC 339 chr4 ENST00000395761.3 CXCL10 UACAGUAUAUAAUUACAACC 340 chr4 ENST00000306602.2 CXCL10 CGUGGACAAAAUUGGCUUGC 341 chr4 ENST00000306602.2 CXCL10 UUGAUUACUAAUGCUGAUGC 342 chr4 ENST00000306602.2 CXCL11 GCUGAAGAUGACAAUGGUGC 343 chr4 ENST00000306621.7 CXCL11 GUUGUUACUUGGGUACAUUA 344 chr4 ENST00000306621.7 CXCL11 AGCGUCCUCUUUUGAACAUG 345 chr4 ENST00000306621.7 CXCL12 CUACACCUUUAAUAAGACUC 346 chr10 ENST00000343575.10 CXCL12 UCAAGACUUACACAAUCUGA 347 chr10 ENST00000343575.10 CXCL12 UGACGUUGGCUCUGGCAACA 348 chr10 ENST00000343575.10 CXCL13 AGGUCUAUUACACAAGCUUG 349 chr4 ENST00000286758.4 CXCL13 UUCGAUCAAUGAAGCGUCUA 350 chr4 ENST00000286758.4 CXCL13 ACUUACAUGAUUUCUUUUCU 351 chr4 ENST00000286758.4 CXCL14 AAUUGGCGCUUGGGUUCCCC 352 chr5 ENST00000337225.5 CXCL14 CUGUACACCGCGCGUGUGGA 353 chr5 ENST00000337225.5 CXCL14 GAGGGGCGCGGCGUGGGAGC 354 chr5 ENST00000337225.5 CXCL16 GCGCUGAGUGGACUGCAAGG 355 chr17 ENST00000293778.10 CXCL16 UACCAGCCCCCCAAUUUCUC 356 chr17 ENST00000293778.10 CXCL16 AAUGUGGACAUGCUUACUCG 357 chr17 ENST00000293778.10 CXCL17 AUUGGUCUCAGAGGGGCCCA 358 chr19 ENST00000601181.5 CXCL17 GACCUUUGCACUCACAUUCU 359 chr19 ENST00000601181.5 CXCL17 CUUCCGACAGGGGUCGCCAG 360 chr19 ENST00000601181.5 CXCL2 GCAGUGGCAGCGGCAGCGAU 361 chr4 ENST00000508487.2 CXCL2 UUCUUCCCUAGGAGCGCCCC 362 chr4 ENST00000508487.2 CXCL2 UUCUUCCCUAGGAGCGCCCC 363 chr4 ENST00000508487.2 CXCL3* UGGCAGCGGAAGCGCGGGGC 364 chr4 ENST00000296026.4 CXCL3* GGGACCUUACAUUCACACUU 365 chr4 ENST00000296026.4 CXCL3* GGGACCUUACAUUCACACUU 366 chr4 ENST00000296026.4 CXCL5 CCCUUUAUAGGGCAGGUUGC 367 chr4 ENST00000296027.4 CXCL5 GCGCCAUGCGCUCUCACCGC 368 chr4 ENST00000296027.4 CXCL5 GAGCUCCUUGUGCGCGCUGU 369 chr4 ENST00000296027.4 CXCL6* GCCCGAAGGACCCGGGACAC 370 chr4 ENST00000226317.9 CXCL6* GGGGCCCCGGCGGCGUCAGC 371 chr4 ENST00000226317.9 CXCL6* UUUUUAUAGGGCAGGUUGCU 372 chr4 ENST00000226317.9 CXCL8 CAACAGGUGCAGUUUUGCCA 373 chr4 ENST00000307407.7 CXCL8 AAAUUUGGGGUGGAAAGGUU 374 chr4 ENST00000307407.7 CXCL8 UACUUACAUAAUUUCUGUGU 375 chr4 ENST00000307407.7 CXCL9* UUUCAAUUUUCUCGCAGGAA 376 chr4 ENST00000264888.5 CXCL9* AUUGUAGGUGGAUAGUCCCU 377 chr4 ENST00000264888.5 CXCL9* GGAACCCCAGUAGUGAGAAA 378 chr4 ENST00000264888.5 CXCR1 GAUGGUAAGCCUGGCGGAAA 379 chr2 ENST00000295683.2 CXCR1 UUGGUCAAGUUUGUUUGUCU 380 chr2 ENST00000295683.2 CXCR1 CUACAGUGGCAUCCUGCUGU 381 chr2 ENST00000295683.2 CXCR2 GUGACAGCUUUGAAGAUUUC 382 chr2 ENST00000318507.6 CXCR2 AUCUAGUAGAAAAGGGGGCA 383 chr2 ENST00000318507.6 CXCR2 UGUGGUCAUUAUCUAUGCCC 384 chr2 ENST00000318507.6 CXCR3{circumflex over ( )} GCAGAAAGAGGAGGCUGUAG 385 chrX ENST00000373693.3 CXCR3{circumflex over ( )} UACCUCCCCGCCCUGCCCAC 386 chrX ENST00000373693.3 CXCR3{circumflex over ( )} AAGAGCUGAAGUUCUCCAGG 387 chrX ENST00000373693.3 CXCR4{circumflex over ( )} CCCAAAGUACCAGUUUGCCA 388 chr2 ENST00000409817.1 CXCR4{circumflex over ( )} AGAGGAGGUCGGCCACUGAC 389 chr2 ENST00000409817.1 CXCR4{circumflex over ( )} UGGAUUGGUCAUCCUGGUCA 390 chr2 ENST00000409817.1 CXCR6** GGAAGUCUUGAUGCUCCUCC 391 chr3 ENST00000304552.4 CXCR6** GGUGUUUGUCUGUGGUCUGG 392 chr3 ENST00000304552.4 CXCR6** CCGUCAGGCUCUGCAACUUA 393 chr3 ENST00000304552.4 EBI3 CACCCUGUGCAGGCUCGGCA 394 chr19 ENST00000221847.5 EBI3 GGAUGUCCAGCUGUUCUCCA 395 chr19 ENST00000221847.5 EBI3 AGCUGCUGCUGGAGCCCCAG 396 chr19 ENST00000221847.5 EDN1 UUUCUCUCCCCAGCAGUCUU 397 chr6 ENST00000379375.5 EDN1 CCACUCCCAGUCCACCCUGG 398 chr6 ENST00000379375.5 EDN1 UCUGCCACCUGGACAUCAUU 399 chr6 ENST00000379375.5 ELANE CACAAUCUCCGAGGCCAGCG 400 chr19 ENST00000263621.1 ELANE GUGUCCCUGCAGCUGCGCGG 401 chr19 ENST00000263621.1 ELANE GCGGCCGACAUGACGAAGUU 402 chr19 ENST00000263621.1 ENG CCGGGCCACUCGGCCGGGUA 403 chr9 ENST00000344849.4 ENG CGCCUUCCAAGUGGCAGCCC 404 chr9 ENST00000344849.4 ENG CGUGCGGCCCAUGUCCUGGC 405 chr9 ENST00000344849.4 EPO CUGUUCUAGAAUGUCCUGCC 406 chr7 ENST00000252723.2 EPO CCCUCUGGGCCUCCCAGUCC 407 chr7 ENST00000252723.2 EPO CCUGGAGAGGUACCUCUUGG 408 chr7 ENST00000252723.2 FAM3B UUACAGCUCCAGUCCCCAAA 409 chr21 ENST00000357985.6 FAM3B UGUAGGCAUAGGUGUCAGAU 410 chr21 ENST00000357985.6 FAM3B GUUAUCCUCAAAGCAGAUUU 411 chr21 ENST00000357985.6 FAM3C CUGAUAGUGCAUUUUACUUU 412 chr7 ENST00000359943.7 FAM3C AUUGUUCUUACCAUUUGCCA 413 chr7 ENST00000359943.7 FAM3C UCCCCCUUCAGUUUAAUGAG 414 chr7 ENST00000359943.7 FAM3D GUGUCUUAGGUACUUACAUG 415 chr3 ENST00000358781.6 FAM3D UUUGCGUUUAAAAUCUGCAG 416 chr3 ENST00000358781.6 FAM3D GAGGUUAAAAAGUACAAGUG 417 chr3 ENST00000358781.6 FAS CACUUGGGCAUUAACACUUU 418 chr10 ENST00000355740.6 FAS UACAGUUGAGACUCAGAACU 419 chr10 ENST00000355740.6 FAS GUGUAACAUACCUGGAGGAC 420 chr10 ENST00000355740.6 FASLG UGGGGAUAUGGGUAAUUGAA 421 chr1 ENST00000367721.2 FASLG AACUGUGCCUGGAGGGGCCC 422 chr1 ENST00000367721.2 FASLG GGUGGUGGCCUCCUUUGACC 423 chr1 ENST00000367721.2 FGF2 CCGCAGGGACCAUGGCAGCC 424 chr4 ENST00000608478.1 FGF2 GGGUCCUUGAAGUGGCCGGG 425 chr4 ENST00000608478.1 FGF2 ACGGCCGAGUUGACGGGGUC 426 chr4 ENST00000608478.1 FLT3LG CUCUAGGAGGAGCUCUGCGG 427 chr19 ENST00000594009.5 FLT3LG GAGCGGCUCAAGACUGUCGC 428 chr19 ENST00000594009.5 FLT3LG GCUGACCUGAAAGGCACAUU 429 chr19 ENST00000594009.5 FOXP3 AGGACCCGAUGCCCAACCCC 430 chrX ENST00000376207.8 FOXP3 CCGAGGGCUUGCCAGGCCUG 431 chrX ENST00000376207.8 FOXP3 CCGAUGCCCAACCCCAGGCC 432 chrX ENST00000376207.8 FOXP3 CCCCAGGCCUGGCAAGCCCU 433 chrX ENST00000376207.8 FZD4 UCGUCCCCGAAGCCCCGCGC 434 chr11 ENST00000531380.1 FZD4 CAGACUGAGACCGACGCCCC 435 chr11 ENST00000531380.1 FZD4 CGAUGCUGGCCAUGGCCUGG 436 chr11 ENST00000531380.1 GATA3 GAGCACAGCCGAGGCCAUGG 437 chr10 ENST00000346208.4 GATA3 CUGGUCCGCCGUCACCUCCA 438 chr10 ENST00000346208.4 GATA3 AGCCGAGGCCAUGGAGGUGA 439 chr10 ENST00000346208.4 GATA3 CGAGGCCAUGGAGGUGACGG 440 chr10 ENST00000346208.4 GBP1 UCCUCACAUCUUCAUAAUGG 441 chr1 ENST00000370473.4 GBP1 CAAGCUGGCUGGAAAGAAAA 442 chr1 ENST00000370473.4 GBP1 UUCUGCCAUUACACAGCCUA 443 chr1 ENST00000370473.4 GDF1 CGUCCGCCGCGAGCCAGACC 444 chr19 ENST00000247005.7 GDF1 GGCCGGUUCCCCCGGUCAUG 445 chr19 ENST00000247005.7 GDF1 GGGGCACGGGGGCGCGGGUC 446 chr19 ENST00000247005.7 GDF10 CCAUGGCUCAUGUCCCCGCU 447 chr10 ENST00000580279.1 GDF10 CGUUGUUUCUGCUGUUGCUC 448 chr10 ENST00000580279.1 GDF10 CGCGGGCAGUGCGGACCAGG 449 chr10 ENST00000580279.1 GDF11 ACGGGGCAGCCGUCCGGCUC 450 chr12 ENST00000257868.9 GDF11 UCUGCGACUUGAUGCUCUCU 451 chr12 ENST00000257868.9 GDF11 CACCACCUCGCGGCUGAUGU 452 chr12 ENST00000257868.9 GDF15 CACCGUCCUGAGUUCUUGCC 453 chr19 ENST00000252809.3 GDF15 GCUCGCCUCGGCCAGAGACA 454 chr19 ENST00000252809.3 GDF15 CUCUCGGAAUCUGGAGUCUU 455 chr19 ENST00000252809.3 GDF2 GCGGGCCUAAGAUGUGUCCU 456 chr10 ENST00000581492.2 GDF2 CUGCAGUGGCUUCCCCUGUA 457 chr10 ENST00000581492.2 GDF2 AGGCACCCCCAGUGGGCUGU 458 chr10 ENST00000581492.2 GDF3 AAAAUUUUCUUCAAGAUAUA 459 chr12 ENST00000329913.3 GDF3 CCUUAUCUAAGCCCAGAAAU 460 chr12 ENST00000329913.3 GDF3 GUUAAUUCUGGCUUUGGGCC 461 chr12 ENST00000329913.3 GDF5 CCCUGGCCUGAAGACGUUCC 462 chr20 ENST00000374369.7 GDF5 UGACUUGGGCCAGAGACCCC 463 chr20 ENST00000374369.7 GDF5 GGUACCAAAGCAAGAAAGUG 464 chr20 ENST00000374369.7 GDF6 GCGGCUUCGCAUGCCCUUGG 465 chr8 ENST00000287020.6 GDF6 GGAUUUGCCCGGUUUCCAGC 466 chr8 ENST00000287020.6 GDF6 GCCCGCCAUGGAUACUCCCA 467 chr8 ENST00000287020.6 GDF7 AGCGCCUGCCGCCCCCGCGA 468 chr2 ENST00000272224.4 GDF7 GCUGGGCCGGUCCGGAGCCC 469 chr2 ENST00000272224.4 GDF7 UGCGGGCGCCGCGGCUGUCC 470 chr2 ENST00000272224.4 GDF9 AUACCUGUUACCUGGUCUCC 471 chr5 ENST00000378673.2 GDF9 AGAGCCGAACAGUGUUGUAG 472 chr5 ENST00000378673.2 GDF9 CUAUAAGACAUAUGCUACCA 473 chr5 ENST00000378673.2 GPI GUCCCGGGUGAGAGCGGCCA 474 chr19 ENST00000356487.9 GPI UCAGCUCGGAGCGGUGCUCG 475 chr19 ENST00000356487.9 GPI CGGCCCGCCCGCACCUGAAG 476 chr19 ENST00000356487.9 GREM1 UAUGAGCCGCACAGCCUACA 477 chr15 ENST00000622074.1 GREM1 CCCUUCAGCAGCCGGCAGCA 478 chr15 ENST00000622074.1 GREM1 UUGUGCUGGGCCUUGUCUGG 479 chr15 ENST00000622074.1 GREM2 CGGUGACCACCAGGGCCUCC 480 chr1 ENST00000318160.4 GREM2 GCAGCAACAACUCGGAGAGA 481 chr1 ENST00000318160.4 GREM2 GCUUUCCCUGUCCUUGUUCC 482 chr1 ENST00000318160.4 GRN CAGGCAGACCAUGUGGACCC 483 chr17 ENST00000053867.7 GRN GCUGGAACGCGGUGCCCAGA 484 chr17 ENST00000053867.7 GRN AGCUGGCUCCUCCGGGGUCC 485 chr17 ENST00000053867.7 HAX1 CACCUUUCUGCAGAACUUCC 486 chr1 ENST00000328703.11 HAX1 UACGGGAGGGACAGACACUU 487 chr1 ENST00000328703.11 HAX1 CCAGUCUGGUGCUGGUUGGG 488 chr1 ENST00000328703.11 HFE2 AGGAGCGGAGGGCUCGACAG 489 chr1 ENST00000336751.10 HFE2 UCAUCAGGAGCACUUCGAGG 490 chr1 ENST00000336751.10 HFE2 CGUACUCAGCAUUGCAGCGG 491 chr1 ENST00000336751.10 HMGB1* GAUACUCACGGAGGCCUCUU 492 chr13 ENST00000339872.8 HMGB1* GAUACUCACGGAGGCCUCUU 493 chr13 ENST00000339872.8 HMGB1* GAUACUCACGGAGGCCUCUU 494 chr13 ENST00000339872.8 HYAL2 GCGUGGGCCACAGUCCUGUG 495 chr3 ENST00000357750.8 HYAL2 UGCUGUGGGCUUGAGCUCCA 496 chr3 ENST00000357750.8 HYAL2 GCAGCCCCCAGCAUGCGGGC 497 chr3 ENST00000357750.8 ICAM3** UCAUGUUCCUGAAGGUGUCC 498 chr19 ENST00000160262.9 ICAM3** CAUGUUCCUGAAGGUGUCCA 499 chr19 ENST00000160262.9 ICAM3** AUGUUCCUGAAGGUGUCCAG 500 chr19 ENST00000160262.9 ICAM3** UCCUGAAGGUGUCCAGGGGC 501 chr19 ENST00000160262.9 ICOS** UUUUAUGCAGGAGAAAUCAA 502 ch2 ENST00000316386.10 ICOS** GAGAUGUUUAUAUUUCACAA 503 ch2 ENST00000316386.10 ICOS** AUGUUUAUAUUUCACAACGG 504 ch2 ENST00000316386.10 ICOS** UUUAAAAUGCAGUUGCUGAA 505 ch2 ENST00000316386.10 IFNA10 CAAACUCCUCCUGGGGGAUU 506 chr9 ENST00000357374.2 IFNA10 CAAACUCCUCCUGGGGGAUU 507 chr9 ENST00000357374.2 IFNA10 CAAACUCCUCCUGGGGGAUU 508 chr9 ENST00000357374.2 IFNA14 CAGGAGGACUUUGAUGCUCA 509 chr9 ENST00000380222.3 IFNA14 AAGCAAAGGGCAAUGCCAUU 510 chr9 ENST00000380222.3 IFNA14 AAGCAAAGGGCAAUGCCAUU 511 chr9 ENST00000380222.3 IFNA16 CAUCUCAUGGAAGGCAGAGA 512 chr9 ENST00000380216.1 IFNA16 AUAUGAUUUCGGAUUCCCCC 513 chr9 ENST00000380216.1 EFNA16 AUAUGAUUUCGGAUUCCCCC 514 chr9 ENST00000380216.1 IFNA2 UCAAGGUCCUCCUGCUACCC 515 chr9 ENST00000380206.3 IFNA2 CACCAGUAAAGCAAAGGUCA 516 chr9 ENST00000380206.3 IFNA2 CACCAGUAAAGCAAAGGUCA 517 chr9 ENST00000380206.3 IFNA5 UUGAUGAUAAUGGCACAAAU 518 chr9 ENST00000610521.1 IFNA5 CUUGCCCUUUGUUUUACUGA 519 chr9 ENST00000610521.1 IFNA5 CUUGCCCUUUGUUUUACUGA 520 chr9 ENST00000610521.1 IFNA6 AGGUCUGCUGAAUCACCUCA 521 chr9 ENST00000380210.1 IFNA6 ACAUGACUUCAGAUUUCCCC 522 chr9 ENST00000380210.1 IFNA6 UCAUGGUCCUCCUGUGACCC 523 chr9 ENST00000380210.1 IFNA8 UACAAGUCAUUCAGCUCUCU 524 chr9 ENST00000380205.1 IFNA8 GUUUAUCAUCAAACUCCUCC 525 chr9 ENST00000380205.1 IFNA8 GUUUAUCAUCAAACUCCUCC 526 chr9 ENST00000380205.1 IFNAR1 UUUACUUUAAAGAACUGGGA 527 chr21 ENST00000270139.7 IFNAR1 GAGUGAAGAAAAGUUGCAUU 528 chr21 ENST00000270139.7 IFNAR1 AAACACUUCUUCAUGGUAUG 529 chr21 ENST00000270139.7 IFNAR2 UAAACCAGAAGAUUUGAAGG 530 chr21 ENST00000342136.8 IFNAR2 UGAGUGGAGAAGCACACACG 531 chr21 ENST00000342136.8 IFNAR2 UCAGUUGCUCACACAAUUUC 532 chr21 ENST00000342136.8 IFNB1 UUGAAUACUGCCUCAAGGAC 533 chr9 ENST00000380232.3 IFNB1 GAAAAUUGCUGCUUCUUUGU 534 chr9 ENST00000380232.3 IFNB1 AGCACAACAGGAGAGCAAUU 535 chr9 ENST00000380232.3 IFNE UGGCCAGAGUGUGUCCUUUU 536 chr9 ENST00000448696.4 IFNE UAGACACUGCUGAAUUGACA 537 chr9 ENST00000448696.4 IFNE CUUGAUUCACUUGUCUUUGC 538 chr9 ENST00000448696.4

IFNG* UUUUUAAUAGUACUUGUUUG 539 chr12 ENST00000229135.3 IFNG* CUUCUUUUACAUAUGGGUCC 540 chr12 ENST00000229135.3 IFNG* GAAAUAUACAAGUUAUAUCU 541 chr12 ENST00000229135.3 IFNGR1** AUUGUACACCCUAAUGUAAC 542 chr6 ENST00000367739.8 IFNGR1** CUCCAUUUACAAAAACUGAA 543 chr6 ENST00000367739.8 IFNGR1** UUUCUGAUAUCCAGUUUAGG 544 chr6 ENST00000367739.8 IFNK UUGUGGCUUGAGAUCCUUAU 545 chr9 ENST00000276943.2 IFNK CGUUCAGUAAGUUACAGUCC 546 chr9 ENST00000276943.2 IFNK UUUUCUCGUAGACAUUCUAC 547 chr9 ENST00000276943.2 IFNL1 AUUUAGCCAUGGCUGCAGCU 548 chr19 ENST00000333625.2 IFNL1 GUGGCAGCCCUUCCCAGUUG 549 chr19 ENST00000333625.2 IFNL1 UAGCGAGCUUCAAGAAGGCC 550 chr19 ENST00000333625.2 IFNL3 CGGGCCUGUGUGAGUCGUCA 551 chr19 ENST00000413851.2 IFNL3 CCAAGACAUCCCCCAGGGCU 552 chr19 ENST00000413851.2 IFNL3 CCAAGACAUCCCCCAGGGCU 553 chr19 ENST00000413851.2 IFNW1 CUCCCUUUUACCAUCUCCUG 554 chr9 ENST00000380229.3 IFNW1 CAUUUGGUGCAGAAGCACCA 555 chr9 ENST00000380229.3 IFNW1 AGAUCCAACAGGGCUAUAGC 556 chr9 ENST00000380229.3 IL10* CGGAGAUCUCGAAGCAUGUU 557 chr1 ENST00000423557.1 IL10* UCAGACUGGGUGCCCUGGCC 558 chr1 ENST00000423557.1 IL10* CUCAGCACUGCUCUGUUGCC 559 chr1 ENST00000423557.1 IL10RA** GGUCUGGCUACAGUUGGAGA 560 chr11 ENST00000227752.7 IL10RA** GGUAGCCAUUGCUGUGGUAC 561 chr11 ENST00000227752.7 IL10RA** GGUGUUGGUGACGGUCCAGU 562 chr11 ENST00000227752.7 IL11 CGUGCCGCAGGUAGGACAGU 563 chr19 ENST00000264563.6 IL11 CGGCUCUAUCCCCAGCUCCC 564 chr19 ENST00000264563.6 IL11 CACUGGGAGCUCUACAGGUA 565 chr19 ENST00000264563.6 IL11RA AGUGUCCUGGUUUCGGGAUG 566 chr9 ENST00000318041.13 IL11RA GCUAGGGCAUGAACUGGUCC 567 chr9 ENST00000318041.13 IL11RA UGCCCCCAAGUGCACCAUCC 568 chr9 ENST00000318041.13 IL12A CCAGGGUAGCCACAAGGAGG 569 chr3 ENST00000305579.6 IL12A GGUCUGGAGUGGCCACGGGG 570 chr3 ENST00000305579.6 IL12A UGACGGCCCUCAGCAGGUUU 571 chr3 ENST00000305579.6 IL12B ACUCUUUGACUUGGAUGGUC 572 chr5 ENST00000231228.2 IL12B GGUGAUACCAUCUUCUUCAG 573 chr5 ENST00000231228.2 IL12B UUUAUGUCGUAGAAUUGGAU 574 chr5 ENST00000231228.2 IL12RB1{circumflex over ( )} CACUUCCUGCGGUGUUGGUG 575 chr19 ENST00000593993.6 IL12RB1{circumflex over ( )} GGAGCACUCGUAACGAUCAC 576 chr19 ENST00000593993.6 IL12RB1{circumflex over ( )} AUCUCUUCCAGGCUCGGCCU 577 chr19 ENST00000593993.6 IL13* CAUGGCGCUUUUGUUGACCA 578 chr5 ENST00000304506.7 IL13* GCCUCCCUCUACAGCCCUCA 579 chr5 ENST00000304506.7 IL13* CGACACUCACCUUCUGGUUC 580 chr5 ENST00000304506.7 IL15 AUGGAAAUACUUCUCAAAUG 581 chr4 ENST00000296545.11 IL15 GGCAUUCAUGUCUUCAUUUU 582 chr4 ENST00000296545.11 IL15 AUGGUCAUGAUGAUUGUCCU 583 chr4 ENST00000296545.11 IL16 CAAAAUUUCGGUCCAUCUCC 584 chr15 ENST00000302987.8 IL16 AGGGCUAGAGCCAUCAUCAC 585 chr15 ENST00000302987.8 IL16 GGAAAAUUCCCUCCUUGCCC 586 chr15 ENST00000302987.8 IL17A{circumflex over ( )} GCUACUGCUGCUGAGCCUGG 587 chr6 ENST00000340057.1 IL17A{circumflex over ( )} UCAACCUGAACAUCCAUAAC 588 chr6 ENST00000340057.1 IL17A{circumflex over ( )} GGAUCGGUUGUAGUAAUCUG 589 chr6 ENST00000340057.1 IL17B{circumflex over ( )} GCUCUGAGCUGUUCCUCAGC 590 chr5 ENST00000261796.3 IL17B{circumflex over ( )} GAAACCGUAUGCCCGCAUGG 591 chr5 ENST00000261796.3 IL17B{circumflex over ( )} CUCUUGCUUUUGGGGCUCCU 592 chr5 ENST00000261796.3 IL17C{circumflex over ( )} UCAGAAACAGGAGGCCGGGG 593 chr16 ENST00000244241.4 IL17C{circumflex over ( )} CGGUACCCCACACUGCUACU 594 chr16 ENST00000244241.4 IL17C{circumflex over ( )} GCACCUCGAGCCAGCAGGUG 595 chr16 ENST00000244241.4 IL17D{circumflex over ( )} CGGCAGCGCCAGCAGGAAGC 596 chr13 ENST00000304920.3 IL17D{circumflex over ( )} GGACCGGCCGGAGGAGCUAC 597 chr13 ENST00000304920.3 IL17D{circumflex over ( )} GUGGAAGGCACUGAGCACGC 598 chr13 ENST00000304920.3 IL17F{circumflex over ( )} GGUAGUAUGAAGCUUGACAU 599 chr6 ENST00000336123.4 IL17F{circumflex over ( )} GAAAAAAGUAUGUCCUACUU 600 chr6 ENST00000336123.4 IL17F{circumflex over ( )} UACUUGCUGCUGUCGAUAUU 601 chr6 ENST00000336123.4 IL18 GGAAAUAAUUUUGUUCUCAC 602 chr11 ENST00000280357.11 IL18 UUACAGCCAUACCUCUAGGC 603 chr11 ENST00000280357.11 IL18 UUAUUUCAGAUAAUGCACCC 604 chr11 ENST00000280357.11 IL18BP GCAGGACCCACAAAGGGCUG 605 chr11 ENST00000260049.9 IL18BP UGUGCUUCUAACUGAGGCAG 606 chr11 ENST00000260049.9 IL18BP GCUGGACACUGCUUAGCUGC 607 chr11 ENST00000260049.9 IL19 AGUUACAGUGUGUUUCCCUU 608 chr1 ENST00000270218.10 IL19 CAGUAGACAACCACGGUCUC 609 chr1 ENST00000270218.10 IL19 CUUGGAAACUCUCUUCUAUA 610 chr1 ENST00000270218.10 IL1A GGAAGGUUCUGAAGAAGAGA 611 chr2 ENST00000263339.3 IL1A GGUAAGCUUGGAUGUUUUAG 612 chr2 ENST00000263339.3 IL1A GCCAUAGCUUACAUGAUAGA 613 chr2 ENST00000263339.3 IL1B* CAUUCUCCUGGAAGGUCUGU 614 chr2 ENST00000263341.6 IL1B* CAUGGCCACAACAACUGACG 615 chr2 ENST00000263341.6 IL1B* CUCUCCGCAGUGCUCCUUCC 616 chr2 ENST00000263341.6 IL1F10 AUCUGCAUACUUCCUAACAG 617 chr2 ENST00000341010.6 IL1F10 CCAGGCAGCGGCUCCCUCCC 618 chr2 ENST00000341010.6 IL1F10 GGCCUCUCACCUCCAGCUGU 619 chr2 ENST00000341010.6 IL1R1** UCCUUUUAAAGAUAAAUGCA 620 chr2 ENST00000410023.5 IL1R1** CUUAACCCAAAUGAACACAA 621 chr2 ENST00000410023.5 IL1R1** UAUCUACAGAACAAGCCUCC 622 chr2 ENST00000410023.5 IL1R2** CCAGAAGCUGCCGGUUUCGU 623 chr2 ENST00000332549.7 IL1R2** UGUAGCCCUGAGGUGCCCCC 624 chr2 ENST00000332549.7 IL1R2** UAAAAAUGACUCUGCUAGGA 625 chr2 ENST00000332549.7 IL1RAPL1** AAUUCUUAAGGAGCAUCUUG 626 chrX ENST00000378993.5 IL1RAPL1** CUCUGUGGAAGAAGGUGACU 627 chrX ENST00000378993.5 IL1RAPL1** UACACUCACCUCGUUUAUGA 628 chrX ENST00000378993.5 IL1RL1** UUUCUUAUUUCAGAAUUGUC 629 chr2 ENST00000233954.5 IL1RL1** AAUGUGAUGACUGAGGACGC 630 chr2 ENST00000233954.5 IL1RL1** ACCCUUGACCGUGAAGGACC 631 chr2 ENST00000233954.5 IL1RN** UUCCCCAGAAAAGAUAGAUG 632 chr2 ENST00000409930.3 IL1RN** ACAGGCACAUCUUCCCUCCA 633 chr2 ENST00000409930.3 IL1RN** AGCAUGUUUUUACCUCCAGC 634 chr2 ENST00000409930.3 IL2 UGUAAUAAUUUUAGUAAGAA 635 chr4 ENST00000226730.4 IL2 ACAACUGGAGCAUUUACUGC 636 chr4 ENST00000226730.4 IL2 GACUUAGUGCAAUGCAAGAC 637 chr4 ENST00000226730.4 IL20 AAGGCUGAAGGCAAGACUAG 638 chr1 ENST00000367096.7 IL20 UGGACUGAAGACACUCAAUU 639 chr1 ENST00000367096.7 IL20 UUCUGAGAUACGGGGCAGUG 640 chr1 ENST00000367096.7 IL20RA CAUCCCCGACCCGCACCUGG 641 chr6 ENST00000316649.9 IL20RA UGUUGCUCCUGGCGGCGCCU 642 chr6 ENST00000316649.9 IL20RA CCGCCGCCCAUGCGGGCUCC 643 chr6 ENST00000316649.9 IL20RB AGUGAGUGAGCACCAGCUGC 644 chr3 ENST00000329582.8 IL20RB UGCCAUACAACCUUCGUGUC 645 chr3 ENST00000329582.8 IL20RB UUCUAUUAAAGGGAUGCUUC 646 chr3 ENST00000329582.8 IL21 GAAAAAUUAUGUGAAUGACU 647 chr4 ENST00000264497.7 IL21 UCAUGUGGCGAUCUUGACCU 648 chr4 ENST00000264497.7 IL21 ACAAUCCUCUCCAUGUUGCC 649 chr4 ENST00000264497.7 IL22{circumflex over ( )} UGGACUUGUCAAGCCUGCAG 650 chr12 ENST00000328087.5 IL22{circumflex over ( )} UCUCUUGGCCCUCUUGGUAC 651 chr12 ENST00000328087.5 IL22{circumflex over ( )} AAGAGCUCACAGAUUUCUGC 652 chr12 ENST00000328087.5 IL22RA1{circumflex over ( )} GAUGUCUGGCUGCCCUAAGU 653 chr1 ENST00000270800.1 IL22RA1{circumflex over ( )} UCUGGACCCAGGGAGCCCGC 654 chr1 ENST00000270800.1 IL22RA1{circumflex over ( )} CAGGGAUCAGGACGUGCUCC 655 chr1 ENST00000270800.1 IL22RA2{circumflex over ( )} UUCUGAGUAGCUCCCAGCCG 656 chr6 ENST00000349184.8 IL22RA2{circumflex over ( )} CUGUAUGUCUGAGGUUUCAC 657 chr6 ENST00000349184.8 IL22RA2{circumflex over ( )} ACAGAUAUGGACAGAGACAA 658 chr6 ENST00000349184.8 IL23A* CUGCUGCCCUGGACAGCUCA 659 chr12 ENST00000228534.5 IL23A* AAGCUGCUGGCACUGAGUCC 660 chr12 ENST00000228534.5 IL23A* CUCACCAUGUGUCCCACUAG 661 chr12 ENST00000228534.5 IL23R** CUGUUGCACAUAUGUAAAAU 662 chr1 ENST00000347310.9 IL23R** GAUGUCAAGAAACAGGCAAA 663 chr1 ENST00000347310.9 IL23R** UAAGUACACUCACCUGUUUC 664 chr1 ENST00000347310.9 IL24 UGAGAGGCUGUCGCCAGCAA 665 chr1 ENST00000294984.6 IL24 CUUCUCUGGAGCCAGGUAUC 666 chr1 ENST00000294984.6 IL24 ACAACCCCCUUCACUUGGCA 667 chr1 ENST00000294984.6 IL25 CCUACAGGUGGUUGCAUUCU 668 chr14 ENST00000329715.2 IL25 GAGGUGUCCUGCCCUUUGCU 669 chr14 ENST00000329715.2 IL25 UGCCUCCCCUAGAGCCUGCU 670 chr14 ENST00000329715.2 IL26 AUAGAGAGCGUCAACAGCUU 671 chr12 ENST00000229134.4 IL26 AGAUUGCUUGUGCUUGGCAA 672 chr12 ENST00000229134.4 IL26 UGCUGGUGAAUUUCAUUUUG 673 chr12 ENST00000229134.4 IL27 CAUUAGGGGGACUUACAAAG 674 chr16 ENST00000356897.1 IL27 GCAGCUCCUGCAGGCUCAGC 675 chr16 ENST00000356897.1 IL27 ACCAGCUUGAACCAGGAGCA 676 chr16 ENST00000356897.1 IL2RA CAGAGCUUGUGCAUUGACAU 677 chr10 ENST00000379959.7 IL2RA GUGACCCGCUUUUUAUUCUG 678 chr10 ENST00000379959.7 IL2RA AUGGCUUUGAAUGUGGCGUG 679 chr10 ENST00000379959.7 IL2RB UGUGGCCUGGGGACAGCGUC 680 chr22 ENST00000216223.9 IL2RB CCCACAGAUGCAACAUAAGC 681 chr22 ENST00000216223.9 IL2RB GUUGUCUCCAGUUCGCCUGA 682 chr22 ENST00000216223.9 IL2RG CAUACCAAUAAUGCAGAGUG 683 chrX ENST00000374202.6 IL2RG UCGAGUACAUGAAUUGCACU 684 chrX ENST00000374202.6 IL2RG GAAACACUGAGGGAGUCAGU 685 chrX ENST00000374202.6 IL3* GCAGGAGCAGGACGGGCAGG 686 chr5 ENST00000296870.2 IL3* CAACGCCCUUGAAGACAAGC 687 chr5 ENST00000296870.2 IL3* CUACUCACCAGCAAAGGCAA 688 chr5 ENST00000296870.2 IL31 CUUUCAAAAGCAUCUUCGAG 689 chr12 ENST00000377035.1 IL31 GUAAACGGACGGGCAACGUG 690 chr12 ENST00000377035.1 IL31 AGAAAGAGCACAGACGUCGA 691 chr12 ENST00000377035.1 IL31RA CAACUUCGCUAAGAACCGUA 692 chr5 ENST00000447346.6 IL31RA AGCUCUGCGAUGUGCGGUCA 693 chr5 ENST00000447346.6 IL31RA CAGUCAUUCCCAUUUUUUCU 694 chr5 ENST00000447346.6 IL32 CUGCCUCUCUUCACAGCACC 695 chr16 ENST00000325568.9 IL32 AGAAUCAGGACGUGGACAGG 696 chr16 ENST00000325568.9 IL32 UCAGGGUGAGAAGGAUGAAG 697 chr16 ENST00000325568.9 IL33 UUGUUUAGAAUCCCAACAGA 698 chr9 ENST00000381434.7 IL33 CUCUGGCCUUAUGAUAAAAA 699 chr9 ENST00000381434.7 IL33 UUUCAGUGAAGGCCUUUUGG 700 chr9 ENST00000381434.7 IL34 UCUUGGGAUCUUCCUUGGCG 701 chr16 ENST00000288098.6 IL34 GCACUCCUCAUUCUGCGUCA 702 chr16 ENST00000288098.6 IL34 CAGGAGCCGACUUCAGUACA 703 chr16 ENST00000288098.6 IL36A CACAUGUCGGCAUGAGAUUA 704 chr2 ENST00000259211.6 IL36A GAUUGAGUCCAUUCAGGCCC 705 chr2 ENST00000259211.6 IL36A ACUCACCUUCAGCUGCAGUG 706 chr2 ENST00000259211.6 IL36B CAAGCCUACUUUGCAGCUUA 707 chr2 ENST00000327407.2 IL36B UAUGGUUUACCUGGGAAUCA 708 chr2 ENST00000327407.2 IL36B GCUAUUAAAUGAAGAGUGAC 709 chr2 ENST00000327407.2 IL36G UCAGUGUGUAAACCUAUUAC 710 chr2 ENST00000259205.4 IL36G CACAAGGUUCUGACCCUGAA 711 chr2 ENST00000259205.4 IL36G CUGUUUGCACUGCUGUGGCU 712 chr2 ENST00000259205.4 IL36RN CACAGGUGAAGAGAUCAGCG 713 chr2 ENST00000346807.7 IL36RN CACCCAGGAUGACGGGGGAC 714 chr2 ENST00000346807.7 IL36RN GGAGCCGACUCUAACACUAG 715 chr2 ENST00000346807.7 IL37 GCUAAUGCAAAGAAGAUCUC 716 chr2 ENST00000263326.7 IL37 AUUCUCCUGGGGGUCUCUAA 717 chr2 ENST00000263326.7 IL37 AACUCUCACCUUCAGCUGAA 718 chr2 ENST00000263326.7 IL4* CAGAGGGGGAAGCAGUUGGG 719 chr5 ENST00000231449.6 IL4* UGAUAUCGCACUUGUGUCCG 720 chr5 ENST00000231449.6 IL4* UACUCACCUUCUGCUCUGUG 721 chr5 ENST00000231449.6 IL5* CAUAAAGAAAAUUACCUCAU 722 chr5 ENST00000231454.5 IL5* UGCAUUGGUGAAAGAGACCU 723 chr5 ENST00000231454.5 IL5* CAUUUGAGUUUGCUAGCUCU 724 chr5 ENST00000231454.5 IL6* CCCUCCGGCACAGGCGCCUU 725 chr7 ENST00000258743.9 IL6* ACAUCUUUGGAAUCUUCUCC 726 chr7 ENST00000258743.9 IL6* AACGAAUUGACAAACAAAUU 727 chr7 ENST00000258743.9 IL6R** CAGUCCGGCCGAAGACUUCC 728 chr1 ENST00000368485.7 IL6R** UAACUGGCAGGAGAACUUCU 729 chr1 ENST00000368485.7 IL6R** CAGCAAAACUCAAACCUUUC 730 chr1 ENST00000368485.7 IL6ST AUUUACCUGGCUCCAAGUUG 731 chr5 ENST00000336909.9 IL6ST UUAUAACACUCUUAAUACUU 732 chr5 ENST00000336909.9 IL6ST UGAUAAAUUAUGUGGCGGAU 733 chr5 ENST00000336909.9 IL7 GGUCAGCAUCGAUCAAUUAU 734 chr8 ENST00000263851.8 IL7 AUGCUACUGGCAACAGAACA 735 chr8 ENST00000263851.8 IL7 UGUCAAAUUUAGUUUCUUUU 736 chr8 ENST00000263851.8 IL9{circumflex over ( )} CUACCUGCAUCUUGUUGAUG 737 chr5 ENST00000274520.1 IL9{circumflex over ( )} UGGACACCCCUGGCCUGCCA 738 chr5 ENST00000274520.1 IL9{circumflex over ( )} UGUCAAGAUGCUUCUGGCCA 739 chr5 ENST00000274520.1 INHA UCAGCAGCAAGAAGAGCAGU 740 chr2 ENST00000243786.2 INHA CCGGGAACUUGUUCUGGCCA 741 chr2 ENST00000243786.2 INHA CCGCGGUGACCAGGGAAGGU 742 chr2 ENST00000243786.2 INHBA UGAACUUAUGGAGCAGACCU 743 chr7 ENST00000242208.4 INHBA GAACGGGUAUGUGGAGAUAG 744 chr7 ENST00000242208.4 INHBA GGGUACCGGCUGGGUGACAU 745 chr7 ENST00000242208.4 INHBB GGCGGCGGCGCGGCAGGCGU 746 chr2 ENST00000295228.3 INHBB GUACGUCGUGCGGCGGCUUC 747 chr2 ENST00000295228.3 INHBB UGUGCCGCUUCACCGCCUCC 748 chr2 ENST00000295228.3 INHBC AAAGGCCAGAAGCAAUGAGG 749 chr12 ENST00000309668.2 INHBC UGGACACUGACCGCCAGCUC 750 chr12 ENST00000309668.2 INHBC GCGGGAGCUGCUUCUUGAUC 751 chr12 ENST00000309668.2 INHBE AAAAGUGAGCAGGGAGCUGU 752 chr12 ENST00000266646.2 INHBE CAAGCAAAGAGUGCCAGGAA 753 chr12 ENST00000266646.2 INHBE CCAGGAGAGUGCGGGACCCU 754 chr12 ENST00000266646.2 ITGA4** CCACCGAGAGCGCAUGGCUU 755 chr2 ENST00000397033.6 ITGA4** GACCGGCCGCCCCUACAACG 756 chr2 ENST00000397033.6 ITGA4** AGCCGAACAGCGUGUUGUGG 757 chr2 ENST00000397033.6 ITGAV** CGGCGAUGGCUUUUCCGCCG 758 chr2 ENST00000261023.7 ITGAV** GUCCCGAGAGAAGAAGCGGG 759 chr2 ENST00000261023.7 ITGAV** GACAGUCCUGCCGAGUACUC 760 chr2 ENST00000261023.7 ITGB1** UGCUGUUCCUUUGCUACGGU 761 chr10 ENST00000302278.7 ITGB1** GAUGACAUAGAAAAUCCCAG 762 chr10 ENST00000302278.7

ITGB1** AUUUAGACAUUUUUACAGGA 763 chr10 ENST00000302278.7 ITGB3** GCGAGGUGAGCCCAGAGGCA 764 chr17 ENST00000559488.5 ITGB3** AGGCCCGAGUACUAGAGGAC 765 chr17 ENST00000559488.5 ITGB3** GGGGACUGACUUGAGUGACC 766 chr17 ENST00000559488.5 KIT** CUCAACCAUCUGUGAGUCCA 767 chr4 ENST00000288135.5 KIT** AUCAGACUUAAUAGUCCGCG 768 chr4 ENST00000288135.5 KIT** AAAGUCCAUUUGACAAAGCC 769 chr4 ENST00000288135.5 KITLG UUUCUUUCACGCACUCCACA 770 chr12 ENST00000228280.9 KITLG AAGUUUUCAAAUAUUUCUGA 771 chr12 ENST00000228280.9 KITLG UCUUGCAGCCAAGUCAUUGU 772 chr12 ENST00000228280.9 KLHL20 GCACCGGGAGCUAUGUGAUG 773 chr1 ENST00000209884.4 KLHL20 UACUUCCGAGCUAUGUUUAC 774 chr1 ENST00000209884.4 KLHL20 UAGCCCUCUCGUCAAUGUCU 775 chr1 ENST00000209884.4 LEFTY1 GCUGCAGCAGGGCCACGUAC 776 chr1 ENST00000272134.5 LEFTY1 CCUCCAUGUCGGCCCUGUCC 777 chr1 ENST00000272134.5 LEFTY1 GUGUUGCCCCUGGCCAGCCC 778 chr1 ENST00000272134.5 LEFTY2 AUGUCGGCCCUGUCCAGUAC 779 chr1 ENST00000366820.9 LEFTY2 CUCCUCGGUCAGGGCCGCCC 780 chr1 ENST00000366820.9 LEFTY2 GCAGCACCAUGUGGCCCCUG 781 chr1 ENST00000366820.9 LIF GUCCCGGGUGAUGUUGCCCA 782 chr22 ENST00000249075.3 LIF UGCCGUUGGCGUGGAAGGGC 783 chr22 ENST00000249075.3 LIF UGUUGGGGAACGGCUCCCCC 784 chr22 ENST00000249075.3 LIFR UGAUGCACUUACCCUUUUUC 785 chr5 ENST00000263409.8 LIFR UAAAUGUUGAUAACAGCCAC 786 chr5 ENST00000263409.8 LIFR GAAACGACCAUCCUGGAUGG 787 chr5 ENST00000263409.8 LTA CCCUAGGGGCUCCCUGGUGU 788 chr6 ENST00000418386.2 LTA GAUGCAUCUUGGGGUGCUGA 789 chr6 ENST00000418386.2 LTA CAGGUGGAUGUUUACCAAUG 790 chr6 ENST00000418386.2 LTB UAUCACUGUCCUGGCUGUGC 791 chr6 ENST00000429299.2 LTB UCCCUCCUGCUAGCUGUGGC 792 chr6 ENST00000429299.2 LTB UUCAGUCUCAAUGGGGGCAC 793 chr6 ENST00000429299.2 LTBP1 AUGGUGGCCAGUGCAGUUCA 794 chr2 ENST00000407925.5 LTBP1 GUUUAGGCACGCUGGCACCA 795 chr2 ENST00000407925.5 LTBP1 GAGGCAAGGUAUGUGUUGAA 796 chr2 ENST00000407925.5 LTBP3 GCCCUCACCCACGCGGAAGC 797 chr11 ENST00000322147.8 LTBP3 AUGACGCUCAUCGGAGAGAA 798 chr11 ENST00000322147.8 LTBP3 CUGCAAGCGGACCUGUCUCA 799 chr11 ENST00000322147.8 LTBP4 CCCUUGAUCUGUCACAAUGG 800 chr19 ENST00000308370.11 LTBP4 GGCCGGGGGCCGGGCGCCCG 801 chr19 ENST00000308370.11 LTBP4 GUGCUCGUCGUCGCGGUGGU 802 chr19 ENST00000308370.11 MAF CAGGAGAAUGGCAUCAGAAC 803 chr16 ENST00000326043.4 MAF CAGGGGACUGGUGGGCAGGU 804 chr16 ENST00000326043.4 MAF UCCAUGGCCAGGGGACUGGU 805 chr16 ENST00000326043.4 MAF CGACCUGCCCACCAGUCCCC 806 chr16 ENST00000326043.4 MIF UUGGUGUUUACGAUGAACAU 807 chr22 ENST00000215754.7 MIF CAGCAGCUGGCGCAGGCCAC 808 chr22 ENST00000215754.7 MIF GCGCGGAACCCCUCGUCCGG 809 chr22 ENST00000215754.7 MINOS1- GGCCACGGGCAUGAUGCUUC 810 chr1 ENST00000602662.1 MINOS1- GAACAGUGCCAGCUUGUUGA 811 chr1 ENST00000602662.1 MINOS1- AGCCGCUGUGGCCCACGAUC 812 chr1 ENST00000602662.1 MSTN UGACGAUUAUCACGCUACAA 813 chr2 ENST00000260950.4 MSTN UUCCCGGAGUGGAGGAGCUU 814 chr2 ENST00000260950.4 MSTN AAUCCUCAGUAAACUUCGUC 815 chr2 ENST00000260950.4 NAMPT GCUGGGGACGAGCGCGCGGC 816 chr7 ENST00000222553.7 NAMPT CUUUACCUUGUAGGAGUCGG 817 chr7 ENST00000222553.7 NAMPT CCGGCCCGAGAUGAAUCCUG 818 chr7 ENST00000222553.7 NBL1 GGCCACGGGCAUGAUGCUUC 819 chr1 ENST00000375136.7 NBL1 GAACAGUGCCAGCUUGUUGA 820 chr1 ENST00000375136.7 NBL1 AGCCGCUGUGGCCCACGAUC 821 chr1 ENST00000375136.7 NDP UUGAGCUACACUUGUACAAU 822 chrX ENST00000378062.5 NDP CAGCUCAUUCAUAAUGGACU 823 chrX ENST00000378062.5 NDP CAGCAGGGAGAGCAUAGAAA 824 chrX ENST00000378062.5 NLRP7 GCCUCUUCCACCUCAGACCA 825 chr19 ENST00000328092.9 NLRP7 GAGUUUCAAAUCCCUUUUAU 826 chr19 ENST00000328092.9 NLRP7 CUGCAGAGUCCACUCUAGCU 827 chr19 ENST00000328092.9 NODAL UGACCAGGCCUCUCUCCAAG 828 chr10 ENST00000287139.7 NODAL GGGACAAAGUGACAGUGAAU 829 chr10 ENST00000287139.7 NODAL CUGUGUCGGGCUUUGGCUGG 830 chr10 ENST00000287139.7 NOG GACCACCACCAGGGCGUAGA 831 chr17 ENST00000332822.4 NOG GGCGGAUGUGGAGAUAGUGC 832 chr17 ENST00000332822.4 NOG UUGGGGUCAAAGAUAGGGUC 833 chr17 ENST00000332822.4 NRG1 GCUACAUCUACAUCCACCAC 834 chr8 ENST00000287842.7 NRG1 AAACUUUCUGUGUGAAUGGA 835 chr8 ENST00000287842.7 NRG1 UUACUUGCACAAGUAUCUCG 836 chr8 ENST00000287842.7 NRP1 UUGCAGAGCAGUGUCUCAGA 837 chr10 ENST00000265371.8 NRP1 GCUGUCGGUGUAAAAAACCA 838 chr10 ENST00000265371.8 NRP1 CCACAGUAACGCCCAAUGUG 839 chr10 ENST00000265371.8 NRP2 CUUUCAGACCCACCGUGCGG 840 chr2 ENST00000357785.9 NRP2 UCUGGUGGGAGGGGUAGUCC 841 chr2 ENST00000357785.9 NRP2 UUGAGGACAAUCUUCUGGUU 842 chr2 ENST00000357785.9 OSM AGGGCCCAGGUGCUUACAUA 843 chr22 ENST00000215781.2 OSM GAUCUGUCUGCUUCUGGAGC 844 chr22 ENST00000215781.2 OSM GUUUCCAAGCAUGGCGAGCA 845 chr22 ENST00000215781.2 OSMR AUUACAGCACCACUGUGAAG 846 chr5 ENST00000274276.7 OSMR CUUUGUAAGAAUAAAGAGUU 847 chr5 ENST00000274276.7 OSMR GAGCAACUGGAGUUCCUGGG 848 chr5 ENST00000274276.7 PARK7 UAGAUUAAGGUCACCGUUGC 849 chr1 ENST00000338639.9 PARK7 CAGGACAAAUGACCACAUCA 850 chr1 ENST00000338639.9 PARK7 CAUGGAGUUAUUCCUUCAUA 851 chr1 ENST00000338639.9 PDPN CAACUGCAAAGUUUGCUGUC 852 chr1 ENST00000294489.10 PDPN CCCCACCGUCGCGCUCCUCC 853 chr1 ENST00000294489.10 PDPN CAGCUCAGAAUCUUGCUGCU 854 chr1 ENST00000294489.10 PF4 UGUGAGGGCUGGCAGCGGCG 855 chr4 ENST00000296029.3 PF4 GUGGCAGGAGCAGCAACCCC 856 chr4 ENST00000296029.3 PF4 CGCAGCAUGAGCUCCGCAGC 857 chr4 ENST00000296029.3 PF4V1 GGCGCGGGUGAGGCGGGACC 858 chr4 ENST00000226524.3 PF4V1 AGAGCAGAAACCAGGCUGGG 859 chr4 ENST00000226524.3 PF4V1 AGAGCAGAAACCAGGCUGGG 860 chr4 ENST00000226524.3 PGLYRP1 CGAUACCACCACAUAGCGUA 861 chr19 ENST00000008938.4 PGLYRP1 CAGGGCCUUCCACUCGUUCC 862 chr19 ENST00000008938.4 PGLYRP1 GCCGCUCUAUGCUGCUUGCC 863 chr19 ENST00000008938.4 PLP2 ACCCUUCCAGAUAUUAUGCC 864 chrX ENST00000376327.5 PLP2 ACCGACAGGGAGGAGUAGCC 865 chrX ENST00000376327.5 PLP2 GGACCCCUUCUCACACUCCA 866 chrX ENST00000376327.5 PPBP UUGGCGAAAGGCAAAGGUAG 867 chr4 ENST00000296028.3 PPBP GUCAUUGCUGCUGACUGCUC 868 chr4 ENST00000296028.3 PPBP AAGGGGUGGUAUCAAGUCUG 869 chr4 ENST00000296028.3 PXDN ACCACAGUUCAGCUCUUCCG 870 chr2 ENST00000252804.8 PXDN GCGUCUGGGAUAUUCACAGA 871 chr2 ENST00000252804.8 PXDN ACUGCGACUGUGAAAUCCUG 872 chr2 ENST00000252804.8 RORC CCGCGUUACAGCGCUGGCUC 873 chr1 ENST00000318247.6 RORC AGUAGGCCGCGUUACAGCGC 874 chr1 ENST00000318247.6 RORC CUGCUGACGGGUGCAGGAGU 875 chr1 ENST00000318247.6 RORC GCAGUUCUGCUGACGGGUGC 876 chr1 ENST00000318247.6 SCG2 AGCCCUGAUCAUUUCAGGAC 877 chr2 ENST00000305409.2 SCG2 CUGGUUCUUUCUGAAGCAGC 878 chr2 ENST00000305409.2 SCG2 UGGCUGAAGCAAAGACCCAC 879 chr2 ENST00000305409.2 SCGB3A1 CCUCUAUGAGGUGGUUCACG 880 chr5 ENST00000292641.3 SCGB3A1 GGUGCCGAGGGGGUUGGCCA 881 chr5 ENST00000292641.3 SCGB3A1 UGCAGCUGCUGCUUUCUUAG 882 chr5 ENST00000292641.3 SECTM1 ACAGCCCAGCAUGGGAGUCC 883 chr17 ENST00000269389.7 SECTM1 CUGGAGCUGCCAGCCGUCCC 884 chr17 ENST00000269389.7 SECTM1 CUUGAUGUUGACAUGGGAGA 885 chr17 ENST00000269389.7 SLURP1 CCCUGACUCCAGUGCACCCA 886 chr8 ENST00000246515.1 SLURP1 CGUCACCAGCGUGGUCAUGC 887 chr8 ENST00000246515.1 SLURP1 CUUGCAGGUGUAGCACUUGA 888 chr8 ENST00000246515.1 SOSTDC1 AUCAAGCCAGAAAUGGAGGC 889 chr7 ENST00000307068.4 SOSTDC1 AGAAAUCCUUUAUUCACAUG 890 chr7 ENST00000307068.4 SOSTDC1 UUAGGAUGCAUGCAAGGGGA 891 chr7 ENST00000307068.4 SP100 UCUGAGAGUCCAUUUUCAGG 892 chr2 ENST00000340126.8 SP100 AGUGACAAAGAUGAUUCGCU 893 chr2 ENST00000340126.8 SP100 ACCCAGUCAGUCUUACCUGU 894 chr2 ENST00000340126.8 SPI1 GUCCCCCACAGACCAUUACU 895 chr11 ENST00000378538.7 SPI1 GGGGGUGGAAGUCCCAGUAA 896 chr11 ENST00000378538.7 SPI1 CGCUGUGCACGUGGUGGGGG 897 chr11 ENST00000378538.7 SPI1 ACUCGCUGUGCACGUGGUGG 898 chr11 ENST00000378538.7 SPP1 AAUGGUGAGACUCAUCAGAC 899 chr4 ENST00000237623.11 SPP1 UCGGUUGCUGGCAGGUCCGU 900 chr4 ENST00000237623.11 SPP1 UGAUGGCCGAGGUGAUAGUG 901 chr4 ENST00000237623.11 TBX21 CCCGCCCCGGAUGGGCAUCG 902 ch17 ENST00000177694.1 TBX21 GGCAUCGUGGAGCCGGGUUG 903 ch17 ENST00000177694.1 TBX21 GGGUUGCGGAGACAUGCUGA 904 ch17 ENST00000177694.1 TBX21 GUCGCUCCCCGGCAUCGGCU 905 ch17 ENST00000177694.1 TCAP GCACUGCCCCUGCUGGUGGU 906 chr17 ENST00000309889.2 TCAP AGUACCAGCUGCCCUACCAG 907 chr17 ENST00000309889.2 TCAP CUCCUUGGUGGCGCCCAUCU 908 chr17 ENST00000309889.2 TGFB1* GCCGCAGCUUGGACAGGAUC 909 chr19 ENST00000221930.5 TGFB1* CUCCAUGUCGAUAGUCUUGC 910 chr19 ENST00000221930.5 TGFB1* AGCAGCCGCAGCCCGGAGGG 911 chr19 ENST00000221930.5 TGFB2* UACCUGCAGCACACUCGAUA 912 chr1 ENST00000366930.8 TGFB2* UCGGGCUCAGGAUAGUCUUC 913 chr1 ENST00000366930.8 TGFB2* CUUCUCCUGGAGCAAGUCCC 914 chr1 ENST00000366930.8 TGFB3* GACAGAUCUUGAGCAAGCUC 915 chr14 ENST00000238682.7 TGFB3* UGGUGCAAGUGGACAGAGAG 916 chr14 ENST00000238682.7 TGFB3* GCACUUGCAAAGGGCUCUGG 917 chr14 ENST00000238682.7 TGFBR1** UUUUCAGUAAAGUCAUCACC 918 chr9 ENST00000374994.8 TGFBR1** CUGCAUCUCACUCAUGUUGA 919 chr9 ENST00000374994.8 TGFBR1** CCUCUUCAUUUGGCACUCGA 920 chr9 ENST00000374994.8 TGFBR2** UCUACUGCUACCGCGUUAAC 921 chr3 ENST00000295754.9 TGFBR2** CGAGCACUGUGCCAUCAUCC 922 chr3 ENST00000295754.9 TGFBR2** GUUGAUGUUGUUGGCACACG 923 chr3 ENST00000295754.9 TGFBR3** CAGCCCAGUUGUGCCUCUGC 924 chr1 ENST00000212355.8 TGFBR3** CAUCAAGGCCUGGACAGGAU 925 chr1 ENST00000212355.8 TGFBR3** CCCUUGGCAGGUCCAGAGCC 926 chr1 ENST00000212355.8 THBS1 UCCUGUCUAACAGAGUCUGG 927 chr15 ENST00000260356.5 THBS1 GUCGGCGCCCAGACCCCUUG 928 chr15 ENST00000260356.5 THBS1 UCAGGUUGGCAUCCUCGAUG 929 chr15 ENST00000260356.5 THNSL2 GAGAAGUGGUCCAUCUGUCC 930 chr2 ENST00000324166.6 THNSL2 UGGCGUCACAUAUGCAUUUA 931 chr2 ENST00000324166.6 THNSL2 UCUUCUCCAGGAAGUACUGC 932 chr2 ENST00000324166.6 THPO CCUGUCCAGAAAGCUGCCCC 933 chr3 ENST00000204615.11 THPO CCAUCACUCCCUCCAGCAGA 934 chr3 ENST00000204615.11 THPO UCUUUCUCAGGAGGAGACCA 935 chr3 ENST00000204615.11 TIMP1 CAGGGGCUCAAAGGGGGCCA 936 chrX ENST00000218388.8 TIMP1 GACACAGGUGCAGGCCCUGC 937 chrX ENST00000218388.8 TIMP1 GGGUGAGGACUCACCGAGGU 938 chrX ENST00000218388.8 TNF* GAUCAUGCUUUCAGUGCUCA 939 chr6 ENST00000449264.2 TNF* CAAGAAGACAGGGGGGCCCC 940 chr6 ENST00000449264.2 TNF* GGCGCCUGCCACGAUCAGGA 941 chr6 ENST00000449264.2 TNFRSF4** CCGGCCCCUGCUCAGGAAGU 942 chr1 ENST00000379236.3 TNFRSF4** UGAGCGGAAGCAGCUGUGCA 943 chr1 ENST00000379236.3 TNFRSF4** GCAGCUGUGCACGGCCACAC 944 chr1 ENST00000379236.3 TNFRSF4** GCGGCAGACUGUGUCCUGUG 945 chr1 ENST00000379236.3 TNFRSF11** GUCUCCCGCAGGCAAGGCCC 946 chr18 ENST00000586569.2 TNFRSF11** CCCCCGGCGCUGCGCGUGCA 947 chr18 ENST00000586569.2 TNFRSF11** CCGCAACACCGAGUGCGCGC 948 chr18 ENST00000586569.2 TNFRSF11** GCCAGCUGUCUGUGUAGUAG 949 chr8 ENST00000297350.8 TNFRSF11** AACAACACUGUACAGCAAAG 950 chr8 ENST00000297350.8 TNFRSF11** ACUUUGGAGGAAACGUUUCC 951 chr8 ENST00000297350.8 TNFRSF1A AGCAAAUCGAAUUAUUUUGA 952 chr12 ENST00000162749.6 TNFRSF1A UUCUCCCUGUCCCCUAGGUG 953 chr12 ENST00000162749.6 TNFRSF1A CCAGGUGCUCCUGGAGCUGU 954 chr12 ENST00000162749.6 TNFRSF9** UGUGAACAGGAUUGUAAACA 955 chr1 ENST00000377507.7 TNFRSF9** CAGAGUGUGACUGCACUCCA 956 chr1 ENST00000377507.7 TNFRSF9** GGGACUUUGUAGGUGUUUUC 957 chr1 ENST00000377507.7 TNFSF9*** GGGGUCCAGUGAAGCGUCAG 958 chr19 ENST00000245817.4 TNFSF9*** AUACGCCUCUGACGCUUCAC 959 chr19 ENST00000245817.4 TNFSF9*** CGGGAGGCCACGGGGCUUCG 960 chr19 ENST00000245817.4 TNFSF9*** CACUGGACCCCGAAGCCCCG 961 chr19 ENST00000245817.4 TNFSF10 CUACCUUUCUAACGAGCUGA 962 chr3 ENST00000241261.6 TNFSF10 GUUCAUACUCUCUUCGUCAU 963 chr3 ENST00000241261.6 TNFSF10 GAAACAAGCAAUGCCACUUU 964 chr3 ENST00000241261.6 TNFSF11 CCAUCUUCUGAUAUUCUAUU 965 chr13 ENST00000398795.6 TNFSF11 AGAUUUUCAAGACACAACUC 966 chr13 ENST00000398795.6 TNFSF11 UUCAUGUAGGAGAAUUAAAC 967 chr13 ENST00000398795.6 TNFSF12 CCGCCCCCAUGGCCGCCCGU 968 chr17 ENST00000293825.10 TNFSF12 CCUGCUGGUCCCGCUCGCGC 969 chr17 ENST00000293825.10 TNFSF12 CCGGGCAUCGCUGUCCGCCC 970 chr17 ENST00000293825.10 TNFSF12- CCGCCCCCAUGGCCGCCCGU 971 chr17 ENST00000293826.4 TNFSF12- CCUGCUGGUCCCGCUCGCGC 972 chr17 ENST00000293826.4 TNFSF12- CCGGGCAUCGCUGUCCGCCC 973 chr17 ENST00000293826.4 TNFSF13 GGGGGGCCCAGUCAGAGAGC 974 chr17 ENST00000338784.8 TNFSF13 CAGAGCCAUGGCACAAGCCA 975 chr17 ENST00000338784.8 TNFSF13 AGAGAGGUGAGCCGGCUGCA 976 chr17 ENST00000338784.8 TNFSF13B UCAUUUCUUCUCUUUUCUUA 977 chr13 ENST00000375887.8 TNFSF13B CUCCAAAGACGGAAAGCUGC 978 chr13 ENST00000375887.8 TNFSF13B CACGGUGGUGUCUUUCUACC 979 chr13 ENST00000375887.8 TNFSF14 CACACCGCCCAGCUGCACCU 980 chr19 ENST00000599359.1 TNFSF14 GGGCCCCAUCGUGGUAGCUG 981 chr19 ENST00000599359.1 TNFSF14 GCUGCCGGUCAAGCUGGAGU 982 chr19 ENST00000599359.1 TNFSF15 UCAUCCCACGGAAUGUGACC 983 chr9 ENST00000374045.4 TNFSF15 AUUUGUUGGUAUAGUUCAUU 984 chr9 ENST00000374045.4 TNFSF15 UGAUUUUUAAAGUGCUGUGU 985 chr9 ENST00000374045.4 TNFSF18 AAUAAAGAUUAGCCAACUGA 986 chr1 ENST00000404377.3 TNFSF18 GCAAAAGAGCCACAGCUUCC 987 chr1 ENST00000404377.3 TNFSF18 AAGUGGCUCAAACACAUUUU 988 chr1 ENST00000404377.3 TNFSF4 CCUCAUCCUUCUGGUAAUGA 989 chr1 ENST00000281834.3 TNFSF4 GUUUUAUCUCAUCUCCCUGA 990 chr1 ENST00000281834.3 TNFSF4 CUAGAAUAUAAGAAGGAGAA 991 chr1 ENST00000281834.3 TNFSF8 UCUGUGCCUUGUCUUCACGG 992 chr9 ENST00000223795.2 TNFSF8 GCUCGUGGUCCCCAGGUGGC 993 chr9 ENST00000223795.2 TNFSF8 UGAGUGCUUGCUGCAGCCCU 994 chr9 ENST00000223795.2 TNFSF9 AUACGCCUCUGACGCUUCAC 995 chr19 ENST00000245817.4 TNFSF9 ACGCGGCAGGCGCGAGCGCG 996 chr19 ENST00000245817.4 TNFSF9 CGUCUUCCUCGCCUGCCCCU 997 chr19 ENST00000245817.4 TRIM16 CUCCUCGGAGAAGCUUGGCA 998 chr17 ENST00000336708.11 TRIM16 GGUCACCCAGCCCAGAUUCU 999 chr17 ENST00000336708.11 TRIM16 AGCCUCCCAGAUGGCUGAGU 1000 chr17 ENST00000336708.11 TSLP UGGAUUUCAGUAAGGCAAUG 1001 chr5 ENST00000344895.3 TSLP AAUGUUCGCCAUGAAAACUA 1002 chr5 ENST00000344895.3 TSLP CAAGGUACAGCAAACGUCUG 1003 chr5 ENST00000344895.3 TWSG1 GUGAGUGCCCGGAAGAGAGA 1004 chr18 ENST00000262120.9 TWSG1 UGUGAAAGUUCUUCUGCAAC 1005 chr18 ENST00000262120.9 TWSG1 ACAGACACAUUCUGGUGGUG 1006 chr18 ENST00000262120.9 TXLNA UAACCAGGGGGGCCCCGGCG 1007 chr1 ENST00000373609.1 TXLNA AGAGAAGUCCCGGACCUAUG 1008 chr1 ENST00000373609.1 TXLNA UGUGUUUGGAUCCCCCUUGG 1009 chr1 ENST00000373609.1 VASN GGCAGCUUUGCCGGCCUGCC 1010 chr16 ENST00000304735.3 VASN ACUCGCCAACCUCAGCAACC 1011 chr16 ENST00000304735.3 VASN AUGAGACCUUCCGUGGCCUG 1012 chr16 ENST00000304735.3 VEGFA CAGGGGCCGGAGCCCGCGCC 1013 chr6 ENST00000425836.6

VEGFA UUCUCGCUUCGGAGGAGCCG 1014 chr6 ENST00000425836.6 VEGFA AAGUGCUAGCUCGGGCCGGG 1015 chr6 ENST00000425836.6 VSTM1 CGAAGCUGAAUUCCCCUUCA 1016 chr19 ENST00000338372.6 VSTM1 UGCGCAAGGUGAACGACUCU 1017 chr19 ENST00000338372.6 VSTM1 UUCAACCACCGAGCUGGGCC 1018 chr19 ENST00000338372.6 WFIKKN1 GCUCCUUCUCACAGCGGUCG 1019 chr16 ENST00000319070.2 WFIKKN1 CCGCUGCUAUAUGGACGCCG 1020 chr16 ENST00000319070.2 WFIKKN1 CCUGCAAGCACGUGCUCAGC 1021 chr16 ENST00000319070.2 WFIKKN2 GUGCAAAGACCGCUGUGAGA 1022 chr17 ENST00000311378.4 WFIKKN2 CCGCUGCUACAUGGAUGCCG 1023 chr17 ENST00000311378.4 WFIKKN2 CCUGCCGCUAUCACUUCACC 1024 chr17 ENST00000311378.4 WNT1 AGACUCCAAGAGUCUGCAAC 1025 chr12 ENST00000293549.3 WNT1 GCGUCUGAUACGCCAAAAUC 1026 chr12 ENST00000293549.3 WNT1 GGCAGUUCCGGAAUCGCCGC 1027 chr12 ENST00000293549.3 WNT2 UGUUGCAAUUCCAGCGGUGC 1028 chr7 ENST00000265441.7 WNT2 CUAAUGGCACGCAUCACAUC 1029 chr7 ENST00000265441.7 WNT2 GAGCUACAGGUGGCUCCUCC 1030 chr7 ENST00000265441.7 WNT5A UGCAGUUCCACCUUCGAUGU 1031 chr3 ENST00000264634.8 WNT5A CUUCUCCGAUGUACUGCAUG 1032 chr3 ENST00000264634.8 WNT5A CCUGCCAGUUGGCUGCAGAG 1033 chr3 ENST00000264634.8 WNT7A AGAGCGCACCGUCUUCGGGA 1034 chr3 ENST00000285018.4 WNT7A ACUGAAACUGACACUCGUCC 1035 chr3 ENST00000285018.4 WNT7A UGGCAGAUCGCCCGCUGUCU 1036 chr3 ENST00000285018.4 XCL1* GGAGUGAAGUCUCAGAUAAG 1037 chr1 ENST00000367818.3 XCL1* GGAGUGAAGUCUCAGAUAAG 1038 chr1 ENST00000367818.3 XCL1* GGAGUGAAGUCUCAGAUAAG 1039 chr1 ENST00000367818.3 XCL2* GAGUGUAUUUCUAUACCUCU 1040 chr1 ENST00000367819.2 XCL2* UAGGGAGUGAAGUCUCACAU 1041 chr1 ENST00000367819.2 XCL2* UAGGGAGUGAAGUCUCACAU 1042 chr1 ENST00000367819.2 ZFP36 CCUCCAUGGUCGGAUGGCAC 1043 chr19 ENST00000597629.1 ZFP36 UCGGAGGGGCUCAGGCUCCA 1044 chr19 ENST00000597629.1 ZFP36 GGAGGGCCGCAGCUGUGGCU 1045 chr19 ENST00000597629.1 *indicates cytokines/chemokines produced by T cells that activate or localize myeloid cells **indicates T cell surface receptor genes that activate myeloid or CAR-T cells ***indicates T cell surface receptors that are integrated into CAR-T cell signaling thus endogenous receptors are redundant {circumflex over ( )}indicates cytokines that drive T cell/CAR-T cell differentiation Bold rows indicate transcription factors that drive T cell/CAR-T cell differentiation

Example 6

Protocol--Nucleofection Using Nucleofector 4D

[0330] 4.times.10.sup.6 cells per reaction are used. EO-115--100 .mu.l transfection volume is programmed, and the entire supplement added to the Nucleofector.TM. Solution P3. Cell culture plates are prepared by filling appropriate number of wells with desired volume of recommended culture media (2 ml in 6 well plate) and pre-incubating/equilibrating plates in a humidified 37.degree. C./5% CO.sub.2 incubator. Beads are magnetically removed (twice to ensure complete removal), then cells counted and cell density determined. The required number of cells are centrifuged at 90.times.g for 10 minutes at room temperature, the supernatant removed completely. Cells are then resuspended in PBS (1 ml) and transferred to a microcentrifuge tube, and the required number of cells centrifuged at 90.times.g for 10 minutes at room temperature. The supernatant is removed completely, and the cell pellet resuspended carefully in complete room temperature 4D Nucleofector.TM. Solution P3, 4.times.10.sup.6 per 100 .mu.l). Twenty .mu.g of gRNA (gGM-CSF) is added to each tube of 15 .mu.g Cas9 mRNA. Then 100 .mu.l of cells is added to each tube of Cas9/gRNA, gently mixed and everything transferred into the Nucleocuvette.TM.. The cuvette is gently tapped to remove bubbles. Electroporation is carried out using program (Human T cell stim EO-115). After run completion, the Nucleocuvette.TM. is carefully removed from the vessel from the retainer using a specialized tool. Cells are resuspended with pre-warmed medium. The media is then taken up from destination well, added to cuvette, and gently pipetted up and down two to three times. This is then transferred to well. This procedure is repeated with media from same well and incubated at 37.degree. C.

[0331] CAR Transduction (Day 2).

[0332] Genome-edited CAR-T cells may then be transduced with one or more CARs targeted to (i.e., that recognizes) one or more targets, for example with a lentivirus containing a CAR construct. Any other suitable method of transduction may be used.

[0333] Protocol--To transduce T cells with lentivirus: One .mu.l of polybrene is added for each ml media (8 mg/ml stock). The required amount of virus is then added to give required M.O.I. Cells and virus are mixed and placed back in incubator at 37.degree. C.

[0334] Assessment of Transduction Efficiency (Day 10).

[0335] Samples of cells may then be assessed for transduction efficiency by taking a 5.times.10.sup.5 cells from each sample and analyzing by flow cytometry. Samples are washed with RB, and 3 .mu.l of anti-CD34 PE antibody added (to detect the CAR as the construct contains human truncated CD34). Thereafter, 5 ul of CD3 APC is added, the cells washed, and flow cytometry performed. CAR-T cells should be CD3.epsilon. positive, CD34 positive.

[0336] Assessment of Genetic Deletion.

[0337] To assess genetic deletion, 5.times.10.sup.5 cells are harvested from each sample and their DNA extracted. Gene editing efficiency is assessed using target sequencing of the target loci using TIDE-analysis or deep sequencing.

[0338] Assessment of Tumor Burden and Cytokine Level.

[0339] T cells are harvested (Day 11). Tumor burden may be imaged in mouse using bioluminescent imaging. 3.times.10.sup.7 CAR-T are injected per mouse I.P.

[0340] Serum cytokine levels (Day 12) are measured, e.g., using the Luminex multiplex cytokine profiling assay to check for elevations in CRS-related cytokines. A 4-hr chromium release assay against targets cells (Raji) may be performed to assess in vitro activity (Day 11).

Example 7

Additional Examples of CAR-Bearing Immune Effector Cells

[0341] Several types of chimeric antigen receptor (CAR)-bearing immune effector cells that are deficient in a cytokine may be made using the methods above. Tables 11-13 below give Examples.

TABLE-US-00012 TABLE 11 Mono, Gene Dual, or CAR Antigen TCR Deleted/ Example Cell Tandem Target(s) Deletion(s) Modifications Suppressed 1 T-Cell Mono CD19 -- -- GM-CSF 2 T-Cell Mono CD19 -- -- CCL2 3 T-Cell Mono CD19 -- -- MCP-2 4 T-Cell Mono CD19 -- -- G-CSF 5 T-Cell Mono CD19 -- -- M-CSF 6 T-Cell Mono CD19 -- -- Il-4 7 T-Cell Mono CD19 -- -- IFN.gamma. 8 T-Cell Mono CD19 -- TRAC GM-CSF 9 T-Cell Mono CD19 -- TRAC CCL2 10 T-Cell Mono CD19 -- TRAC MCP-2 11 T-Cell Mono CD19 -- TRAC G-CSF 12 T-Cell Mono CD19 -- TRAC M-CSF 13 T-Cell Mono CD19 -- TRAC Il-4 14 T-Cell Mono CD19 -- TRAC IFN.gamma. 15 T-Cell Mono CD20 -- -- GM-CSF 16 T-Cell Mono CD20 -- -- CCL2 17 T-Cell Mono CD20 -- -- MCP-2 18 T-Cell Mono CD20 -- -- G-CSF 19 T-Cell Mono CD20 -- -- M-CSF 20 T-Cell Mono CD20 -- -- Il-4 21 T-Cell Mono CD20 -- -- IFN.gamma. 22 T-Cell Mono CD20 -- TRAC GM-CSF 23 T-Cell Mono CD20 -- TRAC CCL2 24 T-Cell Mono CD20 -- TRAC MCP-2 25 T-Cell Mono CD20 -- TRAC G-CSF 26 T-Cell Mono CD20 -- TRAC M-CSF 27 T-Cell Mono CD20 -- TRAC Il-4 28 T-Cell Mono CD20 -- TRAC IFN.gamma. 29 T-Cell Mono BCMA -- -- GM-CSF 30 T-Cell Mono BCMA -- -- CCL2 31 T-Cell Mono BCMA -- -- MCP-2 32 T-Cell Mono BCMA -- -- G-CSF 33 T-Cell Mono BCMA -- -- M-CSF 34 T-Cell Mono BCMA -- -- Il-4 35 T-Cell Mono BCMA -- -- IFN.gamma. 36 T-Cell Mono BCMA -- TRAC GM-CSF 37 T-Cell Mono BCMA -- TRAC CCL2 38 T-Cell Mono BCMA -- TRAC MCP-2 39 T-Cell Mono BCMA -- TRAC G-CSF 40 T-Cell Mono BCMA -- TRAC M-CSF 41 T-Cell Mono BCMA -- TRAC Il-4 42 T-Cell Mono BCMA -- TRAC IFN.gamma. 43 T-Cell Mono Mesothelin -- -- GM-CSF 44 T-Cell Mono Mesothelin -- -- CCL2 45 T-Cell Mono Mesothelin -- -- MCP-2 46 T-Cell Mono Mesothelin -- -- G-CSF 47 T-Cell Mono Mesothelin -- -- M-CSF 48 T-Cell Mono Mesothelin -- -- Il-4 49 T-Cell Mono Mesothelin -- -- IFN.gamma. 50 T-Cell Mono Mesothelin -- TRAC GM-CSF 51 T-Cell Mono Mesothelin -- TRAC CCL2 52 T-Cell Mono Mesothelin -- TRAC MCP-2 53 T-Cell Mono Mesothelin -- TRAC G-CSF 54 T-Cell Mono Mesothelin -- TRAC M-CSF 55 T-Cell Mono Mesothelin -- TRAC Il-4 56 T-Cell Mono Mesothelin -- TRAC IFN.gamma. 57 T-Cell Mono CD7 CD7 TRAC GM-CSF 58 T-Cell Mono CD7 CD7 TRAC CCL2 59 T-Cell Mono CD7 CD7 TRAC MCP-2 60 T-Cell Mono CD7 CD7 TRAC G-CSF 61 T-Cell Mono CD7 CD7 TRAC M-CSF 62 T-Cell Mono CD7 CD7 TRAC Il-4 63 T-Cell Mono CD7 CD7 TRAC IFN.gamma. 64 T-Cell Mono CD3.epsilon. CD3.epsilon. -- GM-CSF 65 T-Cell Mono CD3.epsilon. CD3.epsilon. -- CCL2 66 T-Cell Mono CD3.epsilon. CD3.epsilon. -- MCP-2 67 T-Cell Mono CD3.epsilon. CD3.epsilon. -- G-CSF 68 T-Cell Mono CD3.epsilon. CD3.epsilon. -- M-CSF 69 T-Cell Mono CD3.epsilon. CD3.epsilon. -- Il-4 70 T-Cell Mono CD3.epsilon. CD3.epsilon. -- IFN.gamma. 71 T-Cell Mono CD2 CD2 TRAC GM-CSF 72 T-Cell Mono CD2 CD2 TRAC CCL2 73 T-Cell Mono CD2 CD2 TRAC MCP-2 74 T-Cell Mono CD2 CD2 TRAC G-CSF 75 T-Cell Mono CD2 CD2 TRAC M-CSF 76 T-Cell Mono CD2 CD2 TRAC Il-4 77 T-Cell Mono CD2 CD2 TRAC IFN.gamma. 78 T-Cell Mono CD5 -- TRAC GM-CSF 79 T-Cell Mono CD5 -- TRAC CCL2 80 T-Cell Mono CD5 -- TRAC MCP-2 81 T-Cell Mono CD5 -- TRAC G-CSF 82 T-Cell Mono CD5 -- TRAC M-CSF 83 T-Cell Mono CD5 -- TRAC Il-4 84 T-Cell Mono CD5 -- TRAC IFN.gamma. 85 T-Cell Mono CD5 CD5 TRAC GM-CSF 86 T-Cell Mono CD5 CD5 TRAC CCL2 87 T-Cell Mono CD5 CD5 TRAC MCP-2 88 T-Cell Mono CD5 CD5 TRAC G-CSF 89 T-Cell Mono CD5 CD5 TRAC M-CSF 90 T-Cell Mono CD5 CD5 TRAC Il-4 91 T-Cell Mono CD5 CD5 TRAC IFN.gamma. 92 T-Cell Tandem CD7xCD2 CD7 & CD2 TRAC GM-CSF 93 T-Cell Tandem CD7xCD2 CD7 & CD2 TRAC CCL2 94 T-Cell Tandem CD7xCD2 CD7 & CD2 TRAC MCP-2 95 T-Cell Tandem CD7xCD2 CD7 & CD2 TRAC G-CSF 96 T-Cell Tandem CD7xCD2 CD7 & CD2 TRAC M-CSF 97 T-Cell Tandem CD7xCD2 CD7 & CD2 TRAC Il-4 98 T-Cell Tandem CD7xCD2 CD7 & CD2 TRAC IFN.gamma. 99 T-Cell Tandem CD3.epsilon.xCD2 CD3 & CD2 -- GM-CSF 100 T-Cell Tandem CD3.epsilon.xCD2 CD3 & CD2 -- CCL2 101 T-Cell Tandem CD3.epsilon.xCD2 CD3 & CD2 -- MCP-2 102 T-Cell Tandem CD3.epsilon.xCD2 CD3 & CD2 -- G-CSF 103 T-Cell Tandem CD3.epsilon.xCD2 CD3 & CD2 -- M-CSF 104 T-Cell Tandem CD3.epsilon.xCD2 CD3 & CD2 -- Il-4 105 T-Cell Tandem CD3.epsilon.xCD2 CD3 & CD2 -- IFN.gamma. 106 T-Cell Tandem CD19xCD20 -- TRAC GM-CSF 107 T-Cell Tandem CD19xCD20 -- TRAC CCL2 108 T-Cell Tandem CD19xCD20 -- TRAC MCP-2 109 T-Cell Tandem CD19xCD20 -- TRAC G-CSF 110 T-Cell Tandem CD19xCD20 -- TRAC M-CSF 111 T-Cell Tandem CD19xCD20 -- TRAC Il-4 112 T-Cell Tandem CD19xCD20 -- TRAC IFN.gamma. 113 T-Cell Dual CD7xCD2 CD7 & CD2 TRAC GM-CSF 114 T-Cell Dual CD7xCD2 CD7 & CD2 TRAC CCL2 115 T-Cell Dual CD7xCD2 CD7 & CD2 TRAC MCP-2 116 T-Cell Dual CD7xCD2 CD7 & CD2 TRAC G-CSF 117 T-Cell Dual CD7xCD2 CD7 & CD2 TRAC M-CSF 118 T-Cell Dual CD7xCD2 CD7 & CD2 TRAC Il-4 119 T-Cell Dual CD7xCD2 CD7 & CD2 TRAC IFN.gamma. 120 T-Cell Dual CD3.epsilon.xCD2 CD3 & CD2 -- GM-CSF 121 T-Cell Dual CD3.epsilon.xCD2 CD3 & CD2 -- CCL2 122 T-Cell Dual CD3.epsilon.xCD2 CD3 & CD2 -- MCP-2 123 T-Cell Dual CD3.epsilon.xCD2 CD3 & CD2 -- G-CSF 124 T-Cell Dual CD3.epsilon.xCD2 CD3 & CD2 -- M-CSF 125 T-Cell Dual CD3.epsilon.xCD2 CD3 & CD2 -- Il-4 126 T-Cell Dual CD3.epsilon.xCD2 CD3 & CD2 -- IFN.gamma. 127 T-Cell Dual CD19xCD20 -- TRAC GM-CSF 128 T-Cell Dual CD19xCD20 -- TRAC CCL2 129 T-Cell Dual CD19xCD20 -- TRAC MCP-2 130 T-Cell Dual CD19xCD20 -- TRAC G-CSF 131 T-Cell Dual CD19xCD20 -- TRAC M-CSF 132 T-Cell Dual CD19xCD20 -- TRAC Il-4 133 T-Cell Dual CD19xCD20 -- TRAC IFN.gamma.

TABLE-US-00013 TABLE 12 Mono, Gene Dual, or CAR Antigen Deleted/ Example Cell Tandem Target(s) Deletion(s) Suppressed 134 NK Cell Mono CD19 -- GM-CSF 135 NK Cell Mono CD19 -- CCL2 136 NK Cell Mono CD19 -- MCP-2 137 NK Cell Mono CD19 -- G-CSF 138 NK Cell Mono CD19 -- M-CSF 139 NK Cell Mono CD19 -- Il-4 140 NK Cell Mono CD19 -- IFN.gamma. 141 NK Cell Mono CD19 -- GM-CSF 142 NK Cell Mono CD19 -- CCL2 143 NK Cell Mono CD19 -- MCP-2 144 NK Cell Mono CD19 -- G-CSF 145 NK Cell Mono CD19 -- M-CSF 146 NK Cell Mono CD19 -- Il-4 147 NK Cell Mono CD19 -- IFN.gamma. 148 NK Cell Mono CD20 -- GM-CSF 149 NK Cell Mono CD20 -- CCL2 150 NK Cell Mono CD20 -- MCP-2 151 NK Cell Mono CD20 -- G-CSF 152 NK Cell Mono CD20 -- M-CSF 153 NK Cell Mono CD20 -- Il-4 154 NK Cell Mono CD20 -- IFN.gamma. 155 NK Cell Mono CD20 -- GM-CSF 156 NK Cell Mono CD20 -- CCL2 157 NK Cell Mono CD20 -- MCP-2 158 NK Cell Mono CD20 -- G-CSF 159 NK Cell Mono CD20 -- M-CSF 160 NK Cell Mono CD20 -- Il-4 161 NK Cell Mono CD20 -- IFN.gamma. 162 NK Cell Mono BCMA -- GM-CSF 163 NK Cell Mono BCMA -- CCL2 164 NK Cell Mono BCMA -- MCP-2 165 NK Cell Mono BCMA -- G-CSF 166 NK Cell Mono BCMA -- M-CSF 167 NK Cell Mono BCMA -- Il-4 168 NK Cell Mono BCMA -- IFN.gamma. 169 NK Cell Mono BCMA -- GM-CSF 170 NK Cell Mono BCMA -- CCL2 171 NK Cell Mono BCMA -- MCP-2 172 NK Cell Mono BCMA -- G-CSF 173 NK Cell Mono BCMA -- M-CSF 174 NK Cell Mono BCMA -- Il-4 175 NK Cell Mono BCMA -- IFN.gamma. 176 NK Cell Mono Mesothelin -- GM-CSF 177 NK Cell Mono Mesothelin -- CCL2 178 NK Cell Mono Mesothelin -- MCP-2 179 NK Cell Mono Mesothelin -- G-CSF 180 NK Cell Mono Mesothelin -- M-CSF 181 NK Cell Mono Mesothelin -- Il-4 182 NK Cell Mono Mesothelin -- IFN.gamma. 183 NK Cell Mono Mesothelin -- GM-CSF 184 NK Cell Mono Mesothelin -- CCL2 185 NK Cell Mono Mesothelin -- MCP-2 186 NK Cell Mono Mesothelin -- G-CSF 187 NK Cell Mono Mesothelin -- M-CSF 188 NK Cell Mono Mesothelin -- Il-4 189 NK Cell Mono Mesothelin -- IFN.gamma. 190 NK Cell Mono CD7 CD7 GM-CSF 191 NK Cell Mono CD7 CD7 CCL2 192 NK Cell Mono CD7 CD7 MCP-2 193 NK Cell Mono CD7 CD7 G-CSF 194 NK Cell Mono CD7 CD7 M-CSF 195 NK Cell Mono CD7 CD7 Il-4 196 NK Cell Mono CD7 CD7 IFN.gamma. 197 NK Cell Mono CD3.epsilon. CD3.epsilon. GM-CSF 198 NK Cell Mono CD3.epsilon. CD3.epsilon. CCL2 199 NK Cell Mono CD3.epsilon. CD3.epsilon. MCP-2 200 NK Cell Mono CD3.epsilon. CD3.epsilon. G-CSF 201 NK Cell Mono CD3.epsilon. CD3.epsilon. M-CSF 202 NK Cell Mono CD3.epsilon. CD3.epsilon. Il-4 203 NK Cell Mono CD3.epsilon. CD3.epsilon. IFN.gamma. 204 NK Cell Mono CD2 CD2 GM-CSF 205 NK Cell Mono CD2 CD2 CCL2 206 NK Cell Mono CD2 CD2 MCP-2 207 NK Cell Mono CD2 CD2 G-CSF 208 NK Cell Mono CD2 CD2 M-CSF 209 NK Cell Mono CD2 CD2 Il-4 210 NK Cell Mono CD2 CD2 IFN.gamma. 211 NK Cell Mono CD5 -- GM-CSF 212 NK Cell Mono CD5 -- CCL2 213 NK Cell Mono CD5 -- MCP-2 214 NK Cell Mono CD5 -- G-CSF 215 NK Cell Mono CD5 -- M-CSF 216 NK Cell Mono CD5 -- Il-4 217 NK Cell Mono CD5 -- IFN.gamma. 218 NK Cell Tandem CD7xCD2 CD7 & CD2 GM-CSF 219 NK Cell Tandem CD7xCD2 CD7 & CD2 CCL2 220 NK Cell Tandem CD7xCD2 CD7 & CD2 MCP-2 221 NK Cell Tandem CD7xCD2 CD7 & CD2 G-CSF 222 NK Cell Tandem CD7xCD2 CD7 & CD2 M-CSF 223 NK Cell Tandem CD7xCD2 CD7 & CD2 Il-4 224 NK Cell Tandem CD7xCD2 CD7 & CD2 IFN.gamma. 225 NK Cell Tandem CD3.epsilon.xCD2 CD3 & CD2 GM-C SF 226 NK Cell Tandem CD3.epsilon.xCD2 CD3 & CD2 CCL2 227 NK Cell Tandem CD3.epsilon.xCD2 CD3 & CD2 MCP-2 228 NK Cell Tandem CD3.epsilon.xCD2 CD3 & CD2 G-CSF 229 NK Cell Tandem CD3.epsilon.xCD2 CD3 & CD2 M-CSF 230 NK Cell Tandem CD3.epsilon.xCD2 CD3 & CD2 Il-4 231 NK Cell Tandem CD3.epsilon.xCD2 CD3 & CD2 IFN.gamma. 232 NK Cell Tandem CD19xCD20 -- GM-CSF 233 NK Cell Tandem CD19xCD20 -- CCL2 234 NK Cell Tandem CD19xCD20 -- MCP-2 235 NK Cell Tandem CD19xCD20 -- G-CSF 236 NK Cell Tandem CD19xCD20 -- M-CSF 237 NK Cell Tandem CD19xCD20 -- Il-4 238 NK Cell Tandem CD19xCD20 -- IFN.gamma. 239 NK Cell Dual CD7xCD2 CD7 & CD2 GM-C SF 240 NK Cell Dual CD7xCD2 CD7 & CD2 CCL2 241 NK Cell Dual CD7xCD2 CD7 & CD2 MCP-2 242 NK Cell Dual CD7xCD2 CD7 & CD2 G-CSF 243 NK Cell Dual CD7xCD2 CD7 & CD2 M-CSF 244 NK Cell Dual CD7xCD2 CD7 & CD2 Il-4 245 NK Cell Dual CD7xCD2 CD7 & CD2 IFN.gamma. 246 NK Cell Dual CD3.epsilon.xCD2 CD3 & CD2 GM-CSF 247 NK Cell Dual CD3.epsilon.xCD2 CD3 & CD2 CCL2 248 NK Cell Dual CD3.epsilon.xCD2 CD3 & CD2 MCP-2 249 NK Cell Dual CD3.epsilon.xCD2 CD3 & CD2 G-CSF 250 NK Cell Dual CD3.epsilon.xCD2 CD3 & CD2 M-CSF 251 NK Cell Dual CD3.epsilon.xCD2 CD3 & CD2 Il-4 252 NK Cell Dual CD3.epsilon.xCD2 CD3 & CD2 IFN.gamma. 253 NK Cell Dual CD19xCD20 -- GM-CSF 254 NK Cell Dual CD19xCD20 -- CCL2 255 NK Cell Dual CD19xCD20 -- MCP-2 256 NK Cell Dual CD19xCD20 -- G-CSF 257 NK Cell Dual CD19xCD20 -- M-CSF 258 NK Cell Dual CD19xCD20 -- Il-4 259 NK Cell Dual CD19xCD20 -- IFN.gamma.

TABLE-US-00014 TABLE 13 Mono, Gene Dual, or CAR Antigen Deleted/ Example Cell Tandem Target(s) Deletion(s) Suppressed 260 iNKT Mono CD19 -- GM-CSF 261 iNKT Mono CD19 -- CCL2 262 iNKT Mono CD19 -- MCP-2 263 iNKT Mono CD19 -- G-CSF 264 iNKT Mono CD19 -- M-CSF 265 iNKT Mono CD19 -- Il-4 266 iNKT Mono CD19 -- IFN.gamma. 267 iNKT Mono CD19 -- GM-CSF 268 iNKT Mono CD19 -- CCL2 269 iNKT Mono CD19 -- MCP-2 270 iNKT Mono CD19 -- G-CSF 271 iNKT Mono CD19 -- M-CSF 272 iNKT Mono CD19 -- Il-4 273 iNKT Mono CD19 -- IFN.gamma. 274 iNKT Mono CD20 -- GM-CSF 275 iNKT Mono CD20 -- CCL2 276 iNKT Mono CD20 -- MCP-2 277 iNKT Mono CD20 -- G-CSF 278 iNKT Mono CD20 -- M-CSF 279 iNKT Mono CD20 -- Il-4 280 iNKT Mono CD20 -- IFN.gamma. 281 iNKT Mono CD20 -- GM-CSF 282 iNKT Mono CD20 -- CCL2 283 iNKT Mono CD20 -- MCP-2 284 iNKT Mono CD20 -- G-CSF 285 iNKT Mono CD20 -- M-CSF 286 iNKT Mono CD20 -- Il-4 287 iNKT Mono CD20 -- IFN.gamma. 288 iNKT Mono BCMA -- GM-CSF 289 iNKT Mono BCMA -- CCL2 290 iNKT Mono BCMA -- MCP-2 291 iNKT Mono BCMA -- G-CSF 292 iNKT Mono BCMA -- M-CSF 293 iNKT Mono BCMA -- Il-4 294 iNKT Mono BCMA -- IFN.gamma. 295 iNKT Mono BCMA -- GM-CSF 296 iNKT Mono BCMA -- CCL2 297 iNKT Mono BCMA -- MCP-2 298 iNKT Mono BCMA -- G-CSF 299 iNKT Mono BCMA -- M-CSF 300 iNKT Mono BCMA -- Il-4 301 iNKT Mono BCMA -- IFN.gamma. 302 iNKT Mono Mesothelin -- GM-CSF 303 iNKT Mono Mesothelin -- CCL2 304 iNKT Mono Mesothelin -- MCP-2 305 iNKT Mono Mesothelin -- G-CSF 306 iNKT Mono Mesothelin -- M-CSF 307 iNKT Mono Mesothelin -- Il-4 308 iNKT Mono Mesothelin -- IFN.gamma. 309 iNKT Mono Mesothelin -- GM-CSF 310 iNKT Mono Mesothelin -- CCL2 311 iNKT Mono Mesothelin -- MCP-2 312 iNKT Mono Mesothelin -- G-CSF 313 iNKT Mono Mesothelin -- M-CSF 314 iNKT Mono Mesothelin -- Il-4 315 iNKT Mono Mesothelin -- IFN.gamma. 316 iNKT Mono CD7 CD7 GM-CSF 317 iNKT Mono CD7 CD7 CCL2 318 iNKT Mono CD7 CD7 MCP-2 319 iNKT Mono CD7 CD7 G-CSF 320 iNKT Mono CD7 CD7 M-CSF 321 iNKT Mono CD7 CD7 Il-4 322 iNKT Mono CD7 CD7 IFN.gamma. 323 iNKT Mono CD3.epsilon. CD3.epsilon. GM-CSF 324 iNKT Mono CD3.epsilon. CD3.epsilon. CCL2 325 iNKT Mono CD3.epsilon. CD3.epsilon. MCP-2 326 iNKT Mono CD3.epsilon. CD3.epsilon. G-CSF 327 iNKT Mono CD3.epsilon. CD3.epsilon. M-CSF 328 iNKT Mono CD3.epsilon. CD3.epsilon. Il-4 329 iNKT Mono CD3.epsilon. CD3.epsilon. IFN.gamma. 330 iNKT Mono CD2 CD2 GM-CSF 331 iNKT Mono CD2 CD2 CCL2 332 iNKT Mono CD2 CD2 MCP-2 333 iNKT Mono CD2 CD2 G-CSF 334 iNKT Mono CD2 CD2 M-CSF 335 iNKT Mono CD2 CD2 Il-4 336 iNKT Mono CD2 CD2 IFN.gamma. 337 iNKT Mono CD5 -- GM-CSF 338 iNKT Mono CD5 -- CCL2 339 iNKT Mono CD5 -- MCP-2 340 iNKT Mono CD5 -- G-CSF 341 iNKT Mono CD5 -- M-CSF 342 iNKT Mono CD5 -- Il-4 343 iNKT Mono CD5 -- IFN.gamma. 344 iNKT Mono CD5 CD5 GM-C SF 345 iNKT Mono CD5 CD5 CCL2 346 iNKT Mono CD5 CD5 MCP-2 347 iNKT Mono CD5 CD5 G-CSF 348 iNKT Mono CD5 CD5 M-CSF 349 iNKT Mono CD5 CD5 Il-4 350 iNKT Mono CD5 CD5 IFN.gamma. 351 iNKT Tandem CD7xCD2 CD7 & CD2 GM-C SF 352 iNKT Tandem CD7xCD2 CD7 & CD2 CCL2 353 iNKT Tandem CD7xCD2 CD7 & CD2 MCP-2 354 iNKT Tandem CD7xCD2 CD7 & CD2 G-CSF 355 iNKT Tandem CD7xCD2 CD7 & CD2 M-CSF 356 iNKT Tandem CD7xCD2 CD7 & CD2 Il-4 357 iNKT Tandem CD7xCD2 CD7 & CD2 IFN.gamma. 358 iNKT Tandem CD3.epsilon.xCD2 CD3 & CD2 GM-C SF 359 iNKT Tandem CD3.epsilon.xCD2 CD3 & CD2 CCL2 360 iNKT Tandem CD3.epsilon.xCD2 CD3 & CD2 MCP-2 361 iNKT Tandem CD3.epsilon.xCD2 CD3 & CD2 G-CSF 362 iNKT Tandem CD3.epsilon.xCD2 CD3 & CD2 M-CSF 363 iNKT Tandem CD3.epsilon.xCD2 CD3 & CD2 Il-4 364 iNKT Tandem CD3.epsilon.xCD2 CD3 & CD2 IFN.gamma. 365 iNKT Tandem CD19xCD20 -- GM-C SF 366 iNKT Tandem CD19xCD20 -- CCL2 367 iNKT Tandem CD19xCD20 -- MCP-2 368 iNKT Tandem CD19xCD20 -- G-CSF 369 iNKT Tandem CD19xCD20 -- M-CSF 370 iNKT Tandem CD19xCD20 -- Il-4 371 iNKT Tandem CD19xCD20 -- IFN.gamma. 372 iNKT Dual CD7xCD2 CD7 & CD2 GM-C SF 373 iNKT Dual CD7xCD2 CD7 & CD2 CCL2 374 iNKT Dual CD7xCD2 CD7 & CD2 MCP-2 375 iNKT Dual CD7xCD2 CD7 & CD2 G-CSF 376 iNKT Dual CD7xCD2 CD7 & CD2 M-CSF 377 iNKT Dual CD7xCD2 CD7 & CD2 Il-4 378 iNKT Dual CD7xCD2 CD7 & CD2 IFN.gamma. 379 iNKT Dual CD3.epsilon.xCD2 CD3 & CD2 GM-C SF 380 iNKT Dual CD3.epsilon.xCD2 CD3 & CD2 CCL2 381 iNKT Dual CD3.epsilon.xCD2 CD3 & CD2 MCP-2 382 iNKT Dual CD3.epsilon.xCD2 CD3 & CD2 G-CSF 383 iNKT Dual CD3.epsilon.xCD2 CD3 & CD2 M-CSF 384 iNKT Dual CD3.epsilon.xCD2 CD3 & CD2 Il-4 385 iNKT Dual CD3.epsilon.xCD2 CD3 & CD2 IFN.gamma. 386 iNKT Dual CD19xCD20 -- GM-CSF 387 iNKT Dual CD19xCD20 -- CCL2 388 iNKT Dual CD19xCD20 -- MCP-2 389 iNKT Dual CD19xCD20 -- G-CSF 390 iNKT Dual CD19xCD20 -- M-CSF 391 iNKT Dual CD19xCD20 -- Il-4 392 iNKT Dual CD19xCD20 -- IFN.gamma.

Example 8

Biological Assays

[0342] The following assays, or variations thereon, may be used to assess efficacy of the cytokine-deficient chimeric antigen receptor (CAR)-bearing immune effector cells disclosed herein.

[0343] T-ALL. Testing efficacy of cells in a xenogeneic model of T-ALL: 1.times.10.sup.5 Click Beetle Red luciferase (CBR) labeled CCRF-CEM T-ALL (99% CD7+ by FACS) cells will be injected I.V. into NSG recipients prior to infusion of 2.times.10.sup.6 to 1.times.10.sup.7 CART-bearing immune effector cells or non-targeting CAR19-bearing immune effector cells control cells i.v. on day +4. In contrast to mice receiving CART19-bearing immune effector cells or mice injected with tumor only, mice receiving CART-bearing immune effector cells will demonstrate significantly prolonged survival and reduced tumor burden as determined by bioluminescent imaging.

[0344] Multiple Myeloma. Testing efficacy of iNKT-CAR-CS1 in a xenogeneic model of multiple myeloma: 5.times.10.sup.5 Click Beetle Red luciferase (CBR) labeled MM.1S (99% CS1+ by FACS) cells will be injected I.V. into NSG recipients prior to infusion of 2.times.10.sup.6 to 1.times.10.sup.7 iNKT-CAR-CS1 or non-targeting iNKT-CAR19 control cells i.v. on day +4, or +14 or +28. In contrast to mice receiving iNKT-CAR19 or mice injected with tumor only, mice receiving iNKT-CAR-CS1 will demonstrate significantly prolonged survival and reduced tumor burden as determined by bioluminescent imaging.

[0345] In Vivo Models of Cytokine Release Syndrome and Neurotoxicity

[0346] An in vivo mouse model of CRS is disclosed in Giavridis et al., "CART cell-induced cytokine release syndrome is mediated by macrophages and abated by IL-1 blockade," Nat Med 2018 May 28. For example, in order to initiate CRS as a model system, tumor cells are injected intraperitoneally into immune deficient mice and allowed to develop into a tumor. The mice are then given CAR-T cells targeting the cancerous cells and monitored for several days to induce the onset of CRS, after which mice are sacrificed and cells and tissue obtained for analysis. Mice may also be treated for CRS and monitored for success or failure of treatment (i.e., administering antibodies against cytokines produces as a result of administration of CAR-T cells).

[0347] Analyses appropriate for monitoring CRS in such a model may include monitoring of weight change in the mice after administration of CAR-T cells, percent survival of mice, serum levels of inflammatory factors, i.e., murine SAA3 (equivalent to human C-reactive protein), cytokine levels before and after administration of CAR-T cells, species of origin of pro-inflammatory cytokines (i.e., human versus murine cytokines; and/or percent survival of mice treated with CAR-T cells that received antibodies against specific cytokines.

[0348] Mice that eventually die from CRS symptoms or complications may be classified as having severe CRS, while mice that survive but suffer greater than 10% weight loss may be classified as having non-severe CRS. Using this model, it was discovered that monocytes and macrophages are the main source for IL-6 in CRS.

[0349] Another model useful for assessing both CRS and CAR-T associated neuropathy is disclosed in Norelli, "Monocyte-derived IL-1 and IL-6 are differentially required for cytokine-release syndrome and neurotoxicity due to CART cells," Nat Med 2018 May 28. In this model, human stem cells, such as hematopoietic stem and progenitor cells (HSPCs), are injected into humanized NSG mice, which are immunocompromised transgenic mice expressing human stem cell factor, GM-CSF, and IL-3 to support and enhance hematopoiesis from the injected human stem cells. The mice are given tumor cells to serve as targets for subsequently administered CAR-T cells, and then monitored for CRS symptoms. Following injection of CAR-T cells, these mice exhibit typical symptoms of CRS, including high fever and elevated levels of certain cytokines implicated in CRS, such as IL-1 and/or IL-6. Control of CRS in these mice may be accomplished by blocking the receptor for the cytokine using, for example, antibodies, depletion of cell types expressing the cytokine, or administration of an antagonist of the cytokine. As above, it was determined that monocytes are the main source of the pro-CRS cytokine IL-6, and depletion of monocytes eliminated CRS and protected the mice from death from CRS.

[0350] Other CRS animal models are known in the art and may also be used as deemed appropriate.

[0351] Methods for Inducing and Testing Cytokine Release Syndrome for Control Purposes

[0352] In one model, IL-7 may be directly injected into a mouse or other animal model to induce or initiate CRS for control purposes, as described herein. In yet another example, recombinant or transgenic IL-7 may be expressed in a cell to result in increased IL-7 signaling.

[0353] In a still further example, a constitutively signaling cytokine receptor, such as an IL-7 receptor, may be engineered into an immune effector cell such that the immune effector cell itself triggers IL-7 signaling, but is unresponsive to extracellular IL-7, and initiation of IL-7 signaling of surrounding lymphocytes is avoided. Additionally, co-expressing a constitutively signaling IL-7 receptor with a CAR recognizing a specific disease or tumor antigen results in increased T-cell proliferation, survival, and antitumor activity. A constitutively expressing IL-7 receptor is able to transmit IL-7 signaling without the need for IL-7 ligand or the common gamma .gamma..sub.c chain, a component of the native IL-7 receptor, along with IL-7R.alpha.. This can be accomplished by engineering cysteine and/or proline into the transmembrane domain of the IL-7R.alpha. chain, which results in homodimerization of IL-7R.alpha. and subsequent phosphorylation of JAK1/JAK1, which then activates downstream signaling of IL-7.

[0354] An example of a method for making and testing a genome-edited CAR-T cell deficient at inducing CRS by insertion of selectable marker into gene edited locus is provided below.

Example 9

Insertion of CAR into T Cell Receptor Gene

[0355] A CAR or any protein of interest may be inserted into the gene for the T cell receptor. MacLeod et al. ("Integration of a CD19 CAR into the TCR Alpha Chain Locus Streamlines Production of Allogeneic Gene-Edited CAR T Cells,"Molec Therapy 25(4):P949-961, 2017) reports the generation of allogeneic CART cells by targeting the insertion of a CAR transgene directly into the native TCR locus using an engineered homing endonuclease and an AAV donor template. Anti-CD19 CAR T cells produced in this manner do not express the endogenous cell-surface TCR, exhibit potent effector functions in vitro, and mediate clearance of CD19+ tumors in an in vivo mouse model. The resulting gene-edited CAR T cells exhibit potent anti-tumor activity in vitro and in vivo in preclinical models, suggesting that these cells have potential for safe and efficacious use as adoptive cellular therapy in unrelated patients with CD19+ hematological malignancies.

Example 10

Anti-Cytokine/Chemokine Antibodies to Reduce CRS

[0356] Introduction of immune effector cells to a patient or subject for treatment of cancer often results in CRS due to the production and secretion of cytokines and/or chemokines by the immune effector cells. One way to prevent CRS is to administer antibodies recognizing a specific CRS-inducing cytokine or chemokine to the patient or subject such that the amount of circulating cytokine/chemokine is reduced. For example, as reported by Sachdeva et al., (J Biol Chem 294(14):5430-5437, 2019), administration of anti-GMCSF antibodies reduced the GMCSF secretion thereby effectively reducing CRS. Therefore, administering antibodies recognizing a specific cytokine and/or chemokine can prevent or reduce the occurrence of CRS in a patient or subject.

Example 11

Insertion of CAR into GMCSF Gene

[0357] One exemplary way to prevent CRS is to insert a CAR into a gene for a cytokine or chemokine that is involved in initiation or prolonging of CRS. Disruption or ablation of a cytokine or chemokine gene in a CAR-T or other immune effector cell prevents the initiation of CRS by that particular cytokine or chemokine. One example of such a gene is GMCSF, although other genes involved in initiating or prolonging CRS may also be disrupted in this or a similar manner as described herein. Disruption of the GMCSF gene is described at least in Sachdeva et al. (J Biol Chem 294(14):5430-5437, 2019) and a description of making and testing a CAR-T cell inserted into the GM-CSF gene is provided below. Briefly, a TALEN or other gene-editing enzyme may be designed or engineered to target a cytokine or chemokine gene of choice in a CAR-T cell, and the expression of the gene monitored by methods known in the art. Significant reduction in the expression and secretion of the cytokine or chemokine gene by the CAR-T cell was reported, which implies that the occurrence of CRS would be reduced. Additionally, this approach was found to simultaneously maintain both the proliferation capability and the anti-tumor activity of the CAR-T cell, as assessed by transwell assays and serial killing assays.

[0358] In addition to the use of gene editing to delete a gene such as GM-CSF, antibodies to a cytokine or chemokine causing or contributing to CRS may also be used. For example, an antibody recognizing the GM-CSF protein may be administered to a patient or subject receiving CAR-T therapy. This practice is known in the art, particularly for reduction of CRS as a result of IL-6 signaling using the IL-6R antagonist tocilizumab, however other antibodies or antagonists recognizing cytokines or chemokines, or antagonists of their receptors, may be used as deemed appropriate by a clinician. Appropriate antibodies will bind to the circulating cytokine or chemokine, and antagonists will bind to the native receptors for the cytokine or chemokine, thus preventing downstream CRS-promoting activities in the subject. In some instances, both of these approaches may be employed in a subject, i.e., insertion of a CAR into the gene for a cytokine or chemokine to inactivate the gene, and also administering antibodies against the same cytokine or chemokine to the subject. This approach has been shown to be effective while conferring no negative effects on the activity of the CAR-T cells in vivo or in vitro (Sterner et al., "GM-CSF inhibition reduces cytokine release syndrome and neuroinflammation but enhances CAR-T cell function in xenografts," Blood 133:697-709, 2019).

Example 12

Method of Making and Testing Genome-Edited CAR-T Cells Deficient at Inducing CRS by Insertion of Selectable Marker into Gene Edited Loci

[0359] Inject tumor in SCID-Beige mice (3e6 Raji containing Luciferase) if performing in vivo CRS experiment. This should be completed 3 weeks prior to infusion of CAR-T into mice.

[0360] The following steps may be taken to provide a genome-edited, CRS-resistant, CAR-T cell in which the CAR is expressed from the gene edited loci with a selectable marker disclosed herein. It is not possible to select and purify edited cells based on the deletion of genes that encode internal or secreted proteins, thus a selectable marker is required to enrich for this gene modification. This example describes the making of a CD19CART.DELTA.GMCSF.DELTA.CD3.epsilon. cell, in which the deletion of GM-CSF mitigates risk of CRS and deletion of CD3.epsilon. prevents TCR signaling and graft vs host disease (GvHD). As those of skill in the art will recognize, certain of the steps may be conducted sequentially or out of the order listed below, though perhaps leading to different efficiency.

[0361] Step 1: T Cell Activation (Day 0)

[0362] Purify T cells from leukapheresis chamber using a Miltenyi human PanT isolation kit. Resuspend in media. Count cells. Determine number of human T cell activation CD3/CD28 beads required to obtain 3:1 bead:cell ratio. Wash beads 2.times. with T cell media. Dilute cells at 1.256 cells/mL in hXcyte media. Add human T cell activation CD3/CD28 beads. Aliquot 4 mL/well of 1.256 cell/mL solution into 6 well plate. Incubate cells at 37.degree. C.

[0363] Step 2: CRISPR (Day 2)

[0364] The target gene is genetically deleted and the CAR inserted into the gene edited loci. The DNA double-stranded break can be repaired using homology directed repair using a donor template to repair the break and insert the desired sequence into the edited loci. Target deletion may be accomplished by electroporating with Cas9 mRNA and gRNA against the target(s). The donor template may be a DNA plasmid, or a double-stranded linear DNA, or a single stranded-stranded linear DNA containing homology to the DNA surrounding the double-stranded breaks electroplated with the Cas9/gRNA. In this example the homology arms align to either side of the double-stranded break induced by gRNA GM-CSF. Additionally, a viral vector such as AAV may be used as the source of the donor template. Other techniques, however, could be used to induce DNA double strand breaks. These include other genome editing techniques such as TALENs and mega-nucleases.

[0365] The sequences of the gRNAs for GM-CSF and CD3.epsilon. are as follows:

TABLE-US-00015 hGMCSF gRNA: (SEQ ID NO: 50) 5'_2'OMe(U(ps)A(ps)C(ps))UCAGGUUCAGGAGACGCGUUUUAGA GCUAGAAAUAGCAAGUUAAAAUAAGGCUAGUCCGUUAUCAACUUGAAAAA GUGGCACCGAGUCGGUGC2'OMe(U(ps)U(ps)U(ps)U_3' CD38 gRNA: (SEQ ID NO: 47) 5'_2'OMe(A(ps)G(ps)G(ps))GCAUGUCAAUAUUACUGGUUUUAGA GCUAGAAAUAGCAAGUUAAAAUAAGGCUAGUCCGUUAUCAACUUGAAAAA GUGGCACCGAGUCGGUGC2'OMe(U(ps)U(ps)U(ps)U 3'

TABLE-US-00016 Nucleofection Sample ID gRNA#1 gRNA#2 Cas9 Buffer P3 UCART19 20 .mu.g 20 .mu.g 15 .mu.g Cas9 100 .mu.l gGM-CSF gCD3.epsilon. mRNA

Nucleofection Using Nucleofector 4D:

[0366] Perform nucleofection protocol as described above (Example 6), using 20 .mu.g of each gRNA (gGM-CSF and gCD3.epsilon.) to each tube of 15 .mu.g cas9 mRNA.

[0367] Step 3: Transduction of T Cells with AAV Vector Containing HDR Repair Construct to Introduce CAR and a Selectable Marker into GM-CSF Loci

[0368] Sequences for components of vectors described herein are provided in the sequence listing, such as including, but not limited to, SEQ ID NOs:3048-3064. For example, recombinant AAV6 donor vector (FIG. 3, containing ITR-Right homology arm (SEQ ID NO:51), EF1a promotor (SEQ ID NO:52), CAR19 p2a trCD34 (SEQ ID NO:53), Left homology arm (SEQ ID NO:54), ITR (SEQ ID NO:55), is added to the cell culture 2-4 hrs after electroporation with a MOI between 1.times.10.sup.4 and 1.times.10.sup.6.

[0369] Step 4: Assessment of CRISPR Activity and Td Efficiency (Day 10)

[0370] Take 5.times.10.sup.5 cells from each sample and analyze by flow cytometry. Wash samples with RB. Add 3 .mu.l of anti-CD34 PE antibody (This detects the insertion TrCD34 tag into GM-CSF loci). Add 5 .mu.l of CD3 APC and 2 .mu.l of anti-FAB BV421 (detects CAR transduction). Wash. Perform Flow cytometry. Cells should be CD3.epsilon.-negative, CD34-positive and FAB+. Harvest T cells (Day 11).

[0371] Purification of CAR-T cells. TCR-negative cells can be purified using TCRa/b negative selection to remove TCR positive cells. GM-CSF deleted cells can be enriched using a CD34-positive selection on the Miltenyi Automacs. This enriches the GM-SCF- cells and removes TCR+ cells.

[0372] Step 5: Assessment of CAR-T Activity In Vivo

[0373] Inject 3.times.10.sup.7 CAR-T per mouse I.P. Assess serum cytokine levels. (Day 12, Day 13, Day 14) Measure serum cytokine levels using Luminex multiplex cytokine profiling assay to check for elevations in CRS related cytokines. Perform a 4 hr chromium release assay against targets cells (Raji) to assess in vitro activity (Day 11).

Example 13

Confirmation of GFP Expression with EGFP Integration into CD3e Locus of Jurkats Under Control of CD3e Promotor

[0374] Direct insertion of GFP into the CD3e locus of a Jurkat cell line may be performed using the method details below.

[0375] Days prior: Digest plasmid with PST1 (FIG. 4). Two fragments (3.5 kb and 2.6 kb) are generated upon digestion. Purify using gel extraction kit and ethanol precipitate. Resuspend at 500 ng/.mu.l. This generates donor template `DNA` in table below

[0376] Make and titre AAV. The sequence of the AAV is shown in FIG. 5 and provided in SEQ ID NOs:______. This generates donor template `AAV` in the table below.

[0377] Donor template `plasmid` is shown in the table below.

[0378] Day 0:

[0379] Harvest jurkats and count. Spin cells down @100 g for 10 mins. Transfer cells to 1.5 m microcentrifuge tube and wash in PBS. Spin cells down @100.times.g for 10 mins. Resuspend in pre-warmed buffer SE. Add 100 .mu.l to tube containing gRNA/Cas9. Transfer to nucleocuvette and zap using the Jurkat program on 4D. Transfer to pre-warmed media in 2 ml respective media in a 6-well plate. Return to incubator and expand for 4 days.

TABLE-US-00017 TABLE 14 Nucleofector Cell Cas9 Donor Name Solution Cell line number mRNA gRNA template 1 WT -- Jurkat 4 .times. 10.sup.6 -- 20 .mu.g CD3e -- 2 3.DELTA. SE Jurkat 4 .times. 10.sup.6 15 .mu.g 20 .mu.g CD3e -- 3 P-1ug SE Jurkat 4 .times. 10.sup.6 15 .mu.g 20 .mu.g CD3e Plasmid 1 ug 4 P-2ug SE Jurkat 4 .times. 10.sup.6 15 .mu.g 20 .mu.g CD3e Plasmid 2 ug 5 P-2ug SE Jurkat 4 .times. 10.sup.6 15 .mu.g 20 .mu.g CD3e Plasmid 3 ug 6 D-1ug SE Jurkat 4 .times. 10.sup.6 15 .mu.g 20 .mu.g CD3e DNA 1ug 7 D-2ug SE Jurkat 4 .times. 10.sup.6 15 .mu.g 20 .mu.g CD3e DNA 2ug 8 D-4ug SE Jurkat 4 .times. 10.sup.6 15 .mu.g 20 .mu.g CD3e DNA 3ug 9 AAV Td SE Jurkat 4 .times. 10.sup.6 15 .mu.g 20 .mu.g CD3e AAV 1e4 10 AAV Td SE Jurkat 4 .times. 10.sup.6 15 .mu.g 20 .mu.g CD3e AAV 1e5 11 AAV Td SE Jurkat 4 .times. 10.sup.6 15 .mu.g 20 .mu.g CD3e AAV 1e6

[0380] Day 4: FACS cells for GFP and CD3 APC. Assess editing efficiency by loss of CD3 and integration of the AAV-GFP donor by GFP fluorescence.

Example 14

Method of Making and Testing a Genome-Edited CAR-T Cells by Insertion of CAR into CD3e Loci

[0381] The following steps may be taken to provide a genome-edited CAR-T cell in which the car is expressed from the gene edited loci (CAR-T) disclosed herein. This example describes the making of a CD7CART ACD7 ACD3c cell. As those of skill in the art will recognize, certain of the steps may be conducted sequentially or out of the order listed below, though perhaps leading to different efficiency.

[0382] Step 1: T Cell Activation (Day 0)

[0383] Purify T cells from leukapheresis chamber using Miltenyi human PanT isolation kit. Resuspend in media. Count cells. Determine number of human T cell activation CD3/CD28 beads required to obtain 3:1 bead:cell ratio. Wash beads 2.times. with T cell media. Dilute cells at 1.256 cells/mL in hXcyte media. Add human T cell activation CD3/CD28 beads. Aliquot 4 mL/well of 1.256 cell/mL solution into 6 well plate. Incubate cells at 37.degree. C.

[0384] Step 2: CRISPR (Day 2)

[0385] The target gene is genetically deleted and the CAR inserted into the gene edited loci. The DNA double-stranded break can be repaired using homology-directed repair using a donor template to repair the break and insert the desired sequence into the edited loci. Target deletion may be accomplished by electroporating with Cas9 mRNA and gRNA against the target(s). The donor template may be a DNA plasmid, or double-stranded linear DNA, or single-stranded linear DNA containing homology to the DNA surrounding the double-stranded breaks electroporated with the Cas9/gRNA. Additionally, a viral vector such as AAV may be used as the source of the donor template. Other techniques, however, could be used to induce DNA double-stranded breaks. These include other genome editing techniques, such as TALENs and mega-nucleases.

TABLE-US-00018 Nucleofection Sample ID gRNA#1 gRNA#2 Cas9 Buffer P3 UCART7 20 .mu.g 20 .mu.g 15 .mu.g Cas9 100 .mu.l gCD7 gCD3.epsilon. mRNA

Nucleofection Using Nucleofector 4D:

[0386] Perform nucleofection protocol as described above (Example 6), using 20 .mu.g of each gRNA (gCD7 and gCD3.epsilon.) to each tube of 15 .mu.g Cas9.

[0387] Step 3: Transduction of T cells with AAV vector containing HDR repair construct

[0388] Recombinant AAV6 (or other serotypes of AAV) donor vector is added to the cell culture 2-4 hrs after electroporation with an MOI between 1.times.10.sup.4 and 1.times.10.sup.6.

[0389] Step 4: Assessment of CRISPR Activity and Td Efficiency (Day 10)

[0390] Take 5.times.10.sup.5 cells from each sample and analyze by flow cytometry. Wash samples with RB. Add 3 .mu.l of anti-CD34 PE antibody (This detects the CAR, as the construct contains human truncated CD34). Add 5 .mu.l of CD3 APC and 2 .mu.l of CD7 BV421. Wash. Perform Flow cytometry. Cells should be CD3.epsilon.-negative, CD7-negative and CD34-positive. Harvest T cells (Day 11).

[0391] Purification of CAR-T cells. CD34+ (CAR+) and TCR-negative cells can be purified in a single step using a positive selection of CD34+ cells on a Miltenyi Automacs. This enriches the CAR+ cells and removes and TCR+ cells (as CAR insertion disrupts TCR signaling).

[0392] Step 5: Assessment of CAR-T Activity In Vivo

[0393] Inject tumor in NSG mice (5.times.10.sup.5 MOLT3 or HH: containing Luciferase) if performing in vivo imaging experiment (Day 7).

[0394] Image tumor burden in mouse using bioluminescent imaging. Inject 2.times.10.sup.6 CD34+ CAR-T per mouse I.V. via tail vein or perform a 4hr chromium release assay against targets cell (MOLT3 or HH) (Day 11). Those of skill in the art will appreciate that some flexibility is possible in the specified time frames.

Example 15

Cytokine/Chemokine Gene Silencing Using shRNA

[0395] Similar to siRNAs, short hairpin RNA can be used to knock down or eliminate expression of a cytokine/chemokine/transcription factor gene in an immune effector cell.

[0396] Cherkassky et al. ("Human CAR T cells with cell-intrinsic PD-1 checkpoint blockade resist tumor-mediated inhibition," J Clin Investig 2016; 126:3130-3144) reported use of shRNA to knock down expression of immune checkpoint PD-1 in CD28 mesothelin-specific CAR-T cells, which showed enhanced proliferative function upon antigen stimulation, augmented cytotoxicity, and enhanced cytokine secretion. In addition, a CD19-specific CAR with a PD-1 shRNA lentiviral cassette has been tested for use in CD19-positive B-cell lymphoma. A list of useful shRNAs and their sequences is provided in Tables 15 and 16.

TABLE-US-00019 TABLE 15 5' to 3' (Forward) shRNA sequences for Silencing of Cytokine/Chemokine Genes to Reduce the Incidence of CRS Target SEQ Gene ID Lo- Symbol shRNA Forward Oligo Sequence NO: cation Gene ID No. A2M CCGGAGGCGTCCCTATACCAAATAACTCGAGTTATTTGGTATAGGGACGCCTTTTTTG 1046 chr12 ENST00000318602.11 A2M CCGGAGACTGCATCAATCGTCATAACTCGAGTTATGACGATTGATGCAGTCTTTTTTG 1047 chr12 ENST00000318602.11 A2M CCGGCCTCCAGACATCCTTGAAATACTCGAGTATTTCAAGGATGTCTGGAGGTTTTTG 1048 chr12 ENST00000318602.11 ACKR1 CCGGATCCTGTGGGCCTGGTTTATTCTCGAGAATAAACCAGGCCCACAGGATTTTTTG 1049 chr1 ENST00000368122.2 ACKR1 CCGGTGGCAGAAGCCCTGGCAATTTCTCGAGAAATTGCCAGGGCTTCTGCCATTTTTG 1050 chr1 ENST00000368122.2 ACKR1 CCGGGGCGGATGGTTGAGATCTATCCTCGAGGATAGATCTCAACCATCCGCCTTTTTG 1051 chr1 ENST00000368122.2 ACKR2 CCGGGAGCACTCTTTATACTATTAACTCGAGTTAATAGTATAAAGAGTGCTCTTTTTG 1052 chr3 ENST00000422265.5 ACKR2 CCGGGTGGAACTGCCACGCAGATTTCTCGAGAAATCTGCGTGGCAGTTCCACTTTTTG 1053 chr3 ENST00000422265.5 ACKR2 CCGGCATTGGGTCTTCGGGAGTTTCCTCGAGGAAACTCCCGAAGACCCAATGTTTTTG 1054 chr3 ENST00000422265.5 ACKR3 CCGGCACTATTGGTGTACCTTATAACTCGAGTTATAAGGTACACCAATAGTGTTTTTG 1055 chr2 ENST00000272928.3 ACKR3 CCGGGGCATAGTGCTGACATATATTCTCGAGAATATATGTCAGCACTATGCCTTTTTG 1056 chr2 ENST00000272928.3 ACKR3 CCGGGCCGTTCCCTTCTCCATTATCCTCGAGGATAATGGAGAAGGGAACGGCTTTTTG 1057 chr2 ENST00000272928.3 ACVR1 CCGGTGATAATTCCCTCGACAAATTCTCGAGAATTTGTCGAGGGAATTATCATTTTTG 1058 chr2 ENST00000263640.7 ACVR1 CCGGGCAGAACGTATTTAGCCATTACTCGAGTAATGGCTAAATACGTTCTGCTTTTTG 1059 chr2 ENST00000263640.7 ACVR1 CCGGCTGGTCTGTCTTTGGATAATACTCGAGTATTATCCAAAGACAGACCAGTTTTTG 1060 chr2 ENST00000263640.7 ACVR2B CCGGATGTCACGAGGCCTCTCATACCTCGAGGTATGAGAGGCCTCGTGACATTTTTTG 1061 chr3 ENST00000352511.4 ACVR2B CCGGCCCAGCTCATGAATGACTTTGCTCGAGCAAAGTCATTCATGAGCTGGGTTTTTG 1062 chr3 ENST00000352511.4 ACVR2B CCGGCTTTGGCTTGGCTGTTCGATTCTCGAGAATCGAACAGCCAAGCCAAAGTTTTTG 1063 chr3 ENST00000352511.4 ACVRL1 CCGGCCGGGAGACTGAGATCTATAACTCGAGTTATAGATCTCAGTCTCCCGGTTTTTG 1064 chr12 ENST00000388922.8 ACVRL1 CCGGCAGGAGCACCTGATTCCTTTCCTCGAGGAAAGGAATCAGGTGCTCCTGTTTTTG 1065 chr12 ENST00000388922.8 ACVRL1 CCGGCGTGGAGATCTTCGGTACACACTCGAGTGTGTACCGAAGATCTCCACGTTTTTG 1066 chr12 ENST00000388922.8 ADIPOQ CCGGGTTGGAGGCCTTTAGATATTACTCGAGTAATATCTAAAGGCCTCCAACTTTTTG 1067 chr3 ENST00000320741.6 ADIPOQ CCGGATGCTCATATCAATCCTATAACTCGAGTTATAGGATTGATATGAGCATTTTTTG 1068 chr3 ENST00000320741.6 ADIPOQ CCGGACGGTTAGGAAGTTGATTATTCTCGAGAATAATCAACTTCCTAACCGTTTTTTG 1069 chr3 ENST00000320741.6 AGER CCGGCACACTGCAGTCGGAGCTAATCTCGAGATTAGCTCCGACTGCAGTGTGTTTTTG 1070 chr6 ENST00000375076.8 AGER CCGGGAAGCCAGAAATTGTAGATTCCTCGAGGAATCTACAATTTCTGGCTTCTTTTTG 1071 chr6 ENST00000375076.8 AGER CCGGTGCTGATCCTCCCTGAGATAGCTCGAGCTATCTCAGGGAGGATCAGCATTTTTG 1072 chr6 ENST00000375076.8 AGRN CCGGGAGTTCTGTGTGGAAGATAAACTCGAGTTTATCTTCCACACAGAACTCTTTTTG 1073 chr1 ENST00000379370.6 AGRN CCGGGCGCACGTATGACAGTGATTGCTCGAGCAATCACTGTCATACGTGCGCTTTTTG 1074 chr1 ENST00000379370.6 AGRN CCGGACGACGGAGTCACCTACGAAACTCGAGTTTCGTAGGTGACTCCGTCGTTTTTTG 1075 chr1 ENST00000379370.6 AHR CCGGCGGCATAGAGACCGACTTAATCTCGAGATTAAGTCGGTCTCTATGCCGTTTTTG 1076 chr7 ENST00000242057.8 AHR CCGGGCGGCATAGAGACCGACTTAACTCGAGTTAAGTCGGTCTCTATGCCGCTTTTTG 1077 chr7 ENST00000242057.8 AHR CCGGATCCACAGTCAGCCATAATAACTCGAGTTATTATGGCTGACTGTGGATTTTTTG 1078 chr7 ENST00000242057.8 AHR CCGGACTGCTTAAAGTTGGTATTAACTCGAGTTAATACCAACTTTAAGCAGTTTTTTG 1079 chr7 ENST00000242057.8 AIMP1 CCGGCAGCCTGATCTTCACACTAATCTCGAGATTAGTGTGAAGATCAGGCTGTTTTTG 1080 chr4 ENST00000358008.7 AIMP1 CCGGAGAAGTAGATGTCGGAGAAATCTCGAGATTTCTCCGACATCTACTTCTTTTTTG 1081 chr4 ENST00000358008.7 AIMP1 CCGGGCCAGAGTAACCCTGACTAATCTCGAGATTAGTCAGGGTTACTCTGGCTTTTTG 1082 chr4 ENST00000358008.7 AREG CCGGCCTCTTTCCAGTGGATCATAACTCGAGTTATGATCCACTGGAAAGAGGTTTTTG 1083 chr4 ENST00000395748.7 AREG CCGGTACTCGGCTCAGGCCATTATGCTCGAGCATAATGGCCTGAGCCGAGTATTTTTG 1084 chr4 ENST00000395748.7 AREG CCGGATTCACGGAGAATGCAAATATCTCGAGATATTTGCATTCTCCGTGAATTTTTTG 1085 chr4 ENST00000395748.7 BCL6 CCGGTGTGCCACAGCAATATCTATTCTCGAGAATAGATATTGCTGTGGCACATTTTTG 1086 chr3 ENST00000406870.6 BCL6 CCGGACTGCGTTAAAGGCTCGATTTCTCGAGAAATCGAGCCTTTAACGCAGTTTTTTG 1087 chr3 ENST00000406870.6 BCL6 CCGGCCGGCTCAATAACATCGTTAACTCGAGTTAACGATGTTATTGAGCCGGTTTTTG 1088 chr3 ENST00000406870.6 BCL6 CCGGACAAGCCAGCCGGCTCAATAACTCGAGTTATTGAGCCGGCTGGCTTGTTTTTTG 1089 chr3 ENST00000406870.6 BMP1 CCGGACTGACGAGGACAGCTATATTCTCGAGAATATAGCTGTCCTCGTCAGTTTTTTG 1090 chr8 ENST00000306385.9 BMP1 CCGGGCTCGTAAGTCCTCCATCAAACTCGAGTTTGATGGAGGACTTACGAGCTTTTTG 1091 chr8 ENST00000306385.9 BMP1 CCGGACAGCTGTGCCTACGACTATCCTCGAGGATAGTCGTAGGCACAGCTGTTTTTTG 1092 chr8 ENST00000306385.9 BMP10 CCGGAGCAAGACGGTGTCGACTTTACTCGAGTAAAGTCGACACCGTCTTGCTTTTTTG 1093 chr2 ENST00000295379.1 BMP10 CCGGGCGTCGTCACCTACAAGTTTACTCGAGTAAACTTGTAGGTGACGACGCTTTTTG 1094 chr2 ENST00000295379.1 BMP10 CCGGCATGGCTGAACTTAGGCTATACTCGAGTATAGCCTAAGTTCAGCCATGTTTTTG 1095 chr2 ENST00000295379.1 BMP15 CCGGTACTACGCGATGGTCTCAATTCTCGAGAATTGAGACCATCGCGTAGTATTTTTG 1096 chrX ENST00000252677.3 BMP15 CCGGGCCTTCTTGTTACTCTATTTCCTCGAGGAAATAGAGTAACAAGAAGGCTTTTTG 1097 chrX ENST00000252677.3 BMP15 CCGGATGGAACACAGGGCCCAAATGCTCGAGCATTTGGGCCCTGTGTTCCATTTTTTG 1098 chrX ENST00000252677.3 BMP2 CCGGGATCATCTGAACTCCACTAATCTCGAGATTAGTGGAGTTCAGATGATCTTTTTG 1099 chr20 ENST00000378827.4 BMP2 CCGGCCGGAGATTCTTCTTTAATTTCTCGAGAAATTAAAGAAGAATCTCCGGTTTTTG 1100 chr20 ENST00000378827.4 BMP2 CCGGCAAGATGCTTTAGGAAACAATCTCGAGATTGTTTCCTAAAGCATCTTGTTTTTG 1101 chr20 ENST00000378827.4 BMP3 CCGGCTTACAGGGACACCGGAATTTCTCGAGAAATTCCGGTGTCCCTGTAAGTTTTTG 1102 chr4 ENST00000282701.2 BMP3 CCGGGGCCAAATCTCATCGAGATATCTCGAGATATCTCGATGAGATTTGGCCTTTTTG 1103 chr4 ENST00000282701.2 BMP3 CCGGGTGGATTGAACCTCGGAATTGCTCGAGCAATTCCGAGGTTCAATCCACTTTTTG 1104 chr4 ENST00000282701.2 BMP4 CCGGCCCTGGTCAATTCTGTCAATTCTCGAGAATTGACAGAATTGACCAGGGTTTTTG 1105 chr14 ENST00000245451.8 BMP4 CCGGTCCTTGAGGATAGACAGATATCTCGAGATATCTGTCTATCCTCAAGGATTTTTG 1106 chr14 ENST00000245451.8 BMP4 CCGGAGGGCCAGCATGTCAGGATTACTCGAGTAATCCTGACATGCTGGCCCTTTTTTG 1107 chr14 ENST00000245451.8 BMP5 CCGGTGGACGCAGTATCAACGTAAACTCGAGTTTACGTTGATACTGCGTCCATTTTTG 1108 chr6 ENST00000370830.3 BMP5 CCGGCCAGAAGGATACGCTGCATTTCTCGAGAAATGCAGCGTATCCTTCTGGTTTTTG 1109 chr6 ENST00000370830.3 BMP5 CCGGATGCCACCAACCACGCTATAGCTCGAGCTATAGCGTGGTTGGTGGCATTTTTTG 1110 chr6 ENST00000370830.3 BMP6 CCGGATACAGGAATATGGTTGTAAGCTCGAGCTTACAACCATATTCCTGTATTTTTTG 1111 chr6 ENST00000283147.6 BMP6 CCGGCGCCGACAACAGAGTCGTAATCTCGAGATTACGACTCTGTTGTCGGCGTTTTTG 1112 chr6 ENST00000283147.6 BMP6 CCGGCTGTCTATCAAAGGTAGATTTCTCGAGAAATCTACCTTTGATAGACAGTTTTTG 1113 chr6 ENST00000283147.6 BMP7 CCGGACGTTCCGGATCAGCGTTTATCTCGAGATAAACGCTGATCCGGAACGTTTTTTG 1114 chr20 ENST00000395863.7 BMP7 CCGGACTCGTTTCCAGAGGTAATTACTCGAGTAATTACCTCTGGAAACGAGTTTTTTG 1115 chr20 ENST00000395863.7 BMP7 CCGGACCATCGAGAGTTCCGGTTTGCTCGAGCAAACCGGAACTCTCGATGGTTTTTTG 1116 chr20 ENST00000395863.7 BMP8A CCGGAGGGTGCAGTTAGCATATTAGCTCGAGCTAATATGCTAACTGCACCCTTTTTTG 1117 chr1 ENST00000331593.5 BMP8A CCGGAGCACAGAAGTCCTATCTTAGCTCGAGCTAAGATAGGACTTCTGTGCTTTTTTG 1118 chr1 ENST00000331593.5 BMP8A CCGGAGGTACAACACTGGCCATTTCCTCGAGGAAATGGCCAGTGTTGTACCTTTTTTG 1119 chr1 ENST00000331593.5 BMP8B CCGGCCAAGGCTACTCGGCCTATTACTCGAGTAATAGGCCGAGTAGCCTTGGTTTTTG 1120 chr1 ENST00000372827.7 BMP8B CCGGGACCCTCACAACCACGTACATCTCGAGATGTACGTGGTTGTGAGGGTCTTTTTG 1121 chr1 ENST00000372827.7 BMP8B CCGGCGTTAACATGGTGGAGCGAGACTCGAGTCTCGCTCCACCATGTTAACGTTTTTG 1122 chr1 ENST00000372827.7 BMPR2 CCGGGAACGGCTATGTGCGTTTAAACTCGAGTTTAAACGCACATAGCCGTTCTTTTTG 1123 chr2 ENST00000374580.8 BMPR2 CCGGGCCTATGGAGTGAAATTATTTCTCGAGAAATAATTTCACTCCATAGGCTTTTTG 1124 chr2 ENST00000374580.8 BMPR2 CCGGATTACCACGAGGAGATCATTACTCGAGTAATGATCTCCTCGTGGTAATTTTTTG 1125 chr2 ENST00000374580.8 C10orf99 CCGGCATCATGTGAGGCTCTGTAAACTCGAGTTTACAGAGCCTCACATGATGTTTTTG 1126

chr10 ENST00000372126.3 C10orf99 CCGGCCCAACTCAACAAACCTGAAACTCGAGTTTCAGGTTTGTTGAGTTGGGTTTTTG 1127 chr10 ENST00000372126.3 C10orf99 CCGGGCCATCAACTTTCAGAGCTATCTCGAGATAGCTCTGAAAGTTGATGGCTTTTTG 1128 chr10 ENST00000372126.3 C1QTNF4 CCGGACACCGAGTTCGTCAACATTGCTCGAGCAATGTTGACGAACTCGGTGTTTTTTG 1129 chrll ENST00000302514.3 C1QTNF4 CCGGGCGTAAGACGCTGTCGGTTAACTCGAGTTAACCGACAGCGTCTTACGCTTTTTG 1130 chrll ENST00000302514.3 C1QTNF4 CCGGCGAGGTGCAGGCCATGATTTACTCGAGTAAATCATGGCCTGCACCTCGTTTTTG 1131 chrll ENST00000302514.3 C5 CCGGACGATGGAGCCTGCGTTAATACTCGAGTATTAACGCAGGCTCCATCGTTTTTTG 1132 chr9 ENST00000223642.2 C5 CCGGTCCCGACTTCTGGTCTATTACCTCGAGGTAATAGACCAGAAGTCGGGATTTTTG 1133 chr9 ENST00000223642.2 C5 CCGGGCCCGAGAGAACAGCTTATATCTCGAGATATAAGCTGTTCTCTCGGGCTTTTTG 1134 chr9 ENST00000223642.2 CCL1 CCGGGCAATCCTGTGTTACAGAAATCTCGAGATTTCTGTAACACAGGATTGCTTTTTG 1135 chr17 ENST00000225842.3 CCL1 CCGGCTGCTCCAATGAGGGCTTAATCTCGAGATTAAGCCCTCATTGGAGCAGTTTTTG 1136 chr17 ENST00000225842.3 CCL1 CCGGCCTGAGGGCAATCCTGTGTTACTCGAGTAACACAGGATTGCCCTCAGGTTTTTG 1137 chr17 ENST00000225842.3 CCL11 CCGGCCAACTCCAAAGCCATAAATACTCGAGTATTTATGGCTTTGGAGTTGGTTTTTG 1138 chr17 ENST00000305869.3 CCL11 CCGGCATTCTGAGGTAACCTCATTACTCGAGTAATGAGGTTACCTCAGAATGTTTTTG 1139 chr17 ENST00000305869.3 CCL11 CCGGTCCTCCATGAATATCAGTTATCTCGAGATAACTGATATTCATGGAGGATTTTTG 1140 chr17 ENST00000305869.3 CCL13 CCGGTGGAATACTTCTACCATAATTCTCGAGAATTATGGTAGAAGTATTCCATTTTTG 1141 chr17 ENST00000225844.6 CCL13 CCGGTCAAGCTGGAGTACGTGAAATCTCGAGATTTCACGTACTCCAGCTTGATTTTTG 1142 chr17 ENST00000225844.6 CCL13 CCGGACTCAACGTCCCATCTACTTGCTCGAGCAAGTAGATGGGACGTTGAGTTTTTTG 1143 chr17 ENST00000225844.6 CCL14 CCGGCCTAGGGACCAAGACTGAATCCTCGAGGATTCAGTCTTGGTCCCTAGGTTTTTG 1144 chr17 ENST00000618404.4 CCL14 CCGGCAGCGGATTATGGATTACTATCTCGAGATAGTAATCCATAATCCGCTGTTTTTG 1145 chr17 ENST00000618404.4 CCL14 CCGGCAAGCCCGGAATTGTCTTCATCTCGAGATGAAGACAATTCCGGGCTTGTTTTTG 1146 chr17 ENST00000618404.4 CCL15 CCGGGCTGAAGCCCTACTCAATATACTCGAGTATATTGAGTAGGGCTTCAGCTTTTTG 1147 chr17 ENST00000617897.1 CCL15 CCGGACAGAGTTAATGATGTCAAAGCTCGAGCTTTGACATCATTAACTCTGTTTTTTG 1148 chr17 ENST00000617897.1 CCL15 CCGGATCCCGTGTTCACTCATGAAACTCGAGTTTCATGAGTGAACACGGGATTTTTTG 1149 chr17 ENST00000617897.1 CCL16 CCGGAGGAGAAGTATTTCGAATATTCTCGAGAATATTCGAAATACTTCTCCTTTTTTG 1150 chr17 ENST00000611905.1 CCL16 CCGGAGGAACTTGTCCACGGTTAAACTCGAGTTTAACCGTGGACAAGTTCCTTTTTTG 1151 chr17 ENST00000611905.1 CCL16 CCGGCTGCCTGAAGTATTATGAGAACTCGAGTTCTCATAATACTTCAGGCAGTTTTTG 1152 chr17 ENST00000611905.1 CCL17 CCGGGAGAGTGAAGAATGCAGTTAACTCGAGTTAACTGCATTCTTCACTCTCTTTTTG 1153 chr16 ENST00000219244.8 CCL17 CCGGGAGTACTTCAAGGGAGCCATTCTCGAGAATGGCTCCCTTGAAGTACTCTTTTTG 1154 chr16 ENST00000219244.8 CCL17 CCGGGCAAAGCCTTGAGAGGTCTTGCTCGAGCAAGACCTCTCAAGGCTTTGCTTTTTG 1155 chr16 ENST00000219244.8 CCL18 CCGGTCTATTGTTGAGCTGCATTATCTCGAGATAATGCAGCTCAACAATAGATTTTTG 1156 chr17 ENST00000616054.1 CCL18 CCGGCCTTCAACTCTTCGTACATTCCTCGAGGAATGTACGAAGAGTTGAAGGTTTTTG 1157 chr17 ENST00000616054.1 CCL18 CCGGGTCTATACCTCCTGGCAGATTCTCGAGAATCTGCCAGGAGGTATAGACTTTTTG 1158 chr17 ENST00000616054.1 CCL19 CCGGGAGTCAAGCATTGTGAATTATCTCGAGATAATTCACAATGCTTGACTCTTTTTG 1159 chr9 ENST00000311925.6 CCL19 CCGGGCCGCAGCAGTTAACCTATGACTCGAGTCATAGGTTAACTGCTGCGGCTTTTTG 1160 chr9 ENST00000311925.6 CCL19 CCGGCCAACTCTGAGTGGCACCAATCTCGAGATTGGTGCCACTCAGAGTTGGTTTTTG 1161 chr9 ENST00000311925.6 CCL2 CCGGCCCAGTCACCTGCTGTTATAACTCGAGTTATAACAGCAGGTGACTGGGTTTTTG 1162 chr17 ENST00000225831.4 CCL2 CCGGCCCAGTCACCTGCTGTTATAACTCGAGTTATAACAGCAGGTGACTGGGTTTTTG 1163 chr17 ENST00000225831.4 CCL2 CCGGGCTCGCGAGCTATAGAAGAATCTCGAGATTCTTCTATAGCTCGCGAGCTTTTTG 1164 chr17 ENST00000225831.4 CCL20 CCGGAGTTGTCTGTGTGCGCAAATCCTCGAGGATTTGCGCACACAGACAACTTTTTTG 1165 chr2 ENST00000358813.4 CCL20 CCGGGACCGTATTCTTCATCCTAAACTCGAGTTTAGGATGAAGAATACGGTCTTTTTG 1166 chr2 ENST00000358813.4 CCL20 CCGGAGGGTTTAGTGCTTATCTAATCTCGAGATTAGATAAGCACTAAACCCTTTTTTG 1167 chr2 ENST00000358813.4 CCL21 CCGGCACTCTTTCTCCTGCTTTAACCTCGAGGTTAAAGCAGGAGAAAGAGTGTTTTTG 1168 chr9 ENST00000259607.6 CCL21 CCGGGAGCTATGTGCAGACCCAAAGCTCGAGCTTTGGGTCTGCACATAGCTCTTTTTG 1169 chr9 ENST00000259607.6 CCL21 CCGGCCATCCCAGCTATCCTGTTCTCTCGAGAGAACAGGATAGCTGGGATGGTTTTTG 1170 chr9 ENST00000259607.6 CCL22 CCGGCCCTACCTCCCTGCCATTATACTCGAGTATAATGGCAGGGAGGTAGGGTTTTTG 1171 chr16 ENST00000219235.4 CCL22 CCGGGCGTGGTGAAACACTTCTACTCTCGAGAGTAGAAGTGTTTCACCACGCTTTTTG 1172 chr16 ENST00000219235.4 CCL22 CCGGATGTTGCTGACACCCAGAAAGCTCGAGCTTTCTGGGTGTCAGCAACATTTTTTG 1173 chr16 ENST00000219235.4 CCL23 CCGGCACTCCTGGAGAGTTACTTTGCTCGAGCAAAGTAACTCTCCAGGAGTGTTTTTG 1174 chr17 ENST00000615050.1 CCL23 CCGGCCTTTCTCATGCTGCAGGATTCTCGAGAATCCTGCAGCATGAGAAAGGTTTTTG 1175 chr17 ENST00000615050.1 CCL23 CCGGGAAGCTGGACACACGGATCAACTCGAGTTGATCCGTGTGTCCAGCTTCTTTTTG 1176 chr17 ENST00000615050.1 CCL24 CCGGAGTGATCTTCACCACCAAGAACTCGAGTTCTTGGTGGTGAAGATCACTTTTTTG 1177 chr7 ENST00000222902.6 CCL24 CCGGGTTCTTTGTTTCCAAGAGAATCTCGAGATTCTCTTGGAAACAAAGAACTTTTTG 1178 chr7 ENST00000222902.6 CCL24 CCGGCCTGCTGCATGTTCTTTGTTTCTCGAGAAACAAAGAACATGCAGCAGGTTTTTG 1179 chr7 ENST00000222902.6 CCL25 CCGGGCCGGATCTTTCTCCGATAAACTCGAGTTTATCGGAGAAAGATCCGGCTTTTTG 1180 chr19 ENST00000390669.7 CCL25 CCGGGCTCCTGGATGCTCGAAATAACTCGAGTTATTTCGAGCATCCAGGAGCTTTTTG 1181 chr19 ENST00000390669.7 CCL25 CCGGCCCTCCTGATATCAGCTAATTCTCGAGAATTAGCTGATATCAGGAGGGTTTTTG 1182 chr19 ENST00000390669.7 CCL26 CCGGCACACGTGGGAGTGACATATCCTCGAGGATATGTCACTCCCACGTGTGTTTTTG 1183 chr7 ENST00000005180.8 CCL26 CCGGTCCGAAACAATTGTGACTCAGCTCGAGCTGAGTCACAATTGTTTCGGATTTTTG 1184 chr7 ENST00000005180.8 CCL26 CCGGGCTGTGATATTCACTACCAAACTCGAGTTTGGTAGTGAATATCACAGCTTTTTG 1185 chr7 ENST00000005180.8 CCL27 CCGGTTCGTGCTTCACCTGGCTCAACTCGAGTTGAGCCAGGTGAAGCACGAATTTTTG 1186 chr9 ENST00000259631.4 CCL27 CCGGCCGAAAGCCACTCTCAGACAACTCGAGTTGTCTGAGAGTGGCTTTCGGTTTTTG 1187 chr9 ENST00000259631.4 CCL27 CCGGCAAGCTACTGAGGAAGGTCATCTCGAGATGACCTTCCTCAGTAGCTTGTTTTTG 1188 chr9 ENST00000259631.4 CCL28 CCGGCGGAGGTTTCACATCATATTTCTCGAGAAATATGATGTGAAACCTCCGTTTTTG 1189 chr5 ENST00000361115.4 CCL28 CCGGCACGAAACATACGGCCATAAACTCGAGTTTATGGCCGTATGTTTCGTGTTTTTG 1190 chr5 ENST00000361115.4 CCL28 CCGGTTAGAGAGTCTACAGATAAATCTCGAGATTTATCTGTAGACTCTCTAATTTTTG 1191 chr5 ENST00000361115.4 CCL3 CCGGCCGGCAGATTCCACAGAATTTCTCGAGAAATTCTGTGGAATCTGCCGGTTTTTG 1192 chr17 ENST00000613922.1 CCL3 CCGGTTCGATTTCACAGTGTGTTTGCTCGAGCAAACACACTGTGAAATCGAATTTTTG 1193 chr17 ENST00000613922.1 CCL3 CCGGCAACCAGTTCTCTGCATCACTCTCGAGAGTGATGCAGAGAACTGGTTGTTTTTG 1194 chr17 ENST00000613922.1 CCL4 CCGGATGTGCCGTGTTATTGTATTACTCGAGTAATACAATAACACGGCACATTTTTTG 1195 chr17 ENST00000615863.1 CCL4 CCGGTCCTGTCCCTTCTCTTAATTTCTCGAGAAATTAAGAGAAGGGACAGGATTTTTG 1196 chr17 ENST00000615863.1 CCL4 CCGGCTGTGCTGATCCCAGTGAATCCTCGAGGATTCACTGGGATCAGCACAGTTTTTG 1197 chr17 ENST00000615863.1 CCL5 CCGGTGAACCTGAACTTACACAAATCTCGAGATTTGTGTAAGTTCAGGTTCATTTTTG 1198 chr17 ENST00000603197.5 CCL5 CCGGCCTGCTGCTTTGCCTACATTGCTCGAGCAATGTAGGCAAAGCAGCAGGTTTTTG 1199 chr17 ENST00000603197.5 CCL5 CCGGCTACCACACAGCAGCAGTTACCTCGAGGTAACTGCTGCTGTGTGGTAGTTTTTG 1200 chr17 ENST00000603197.5 CCL7 CCGGCATAAAGCCTTGGATGTATATCTCGAGATATACATCCAAGGCTTTATGTTTTTG 1201 chr17 ENST00000378569.2 CCL7 CCGGGCTGCTACAGATTTATCAATACTCGAGTATTGATAAATCTGTAGCAGCTTTTTG 1202 chr17 ENST00000378569.2 CCL7 CCGGTCTAAGGAATATGAGCTTTATCTCGAGATAAAGCTCATATTCCTTAGATTTTTG 1203 chr17 ENST00000378569.2 CCL8 CCGGGCTGCTTTAACGTGATCAATACTCGAGTATTGATCACGTTAAAGCAGCTTTTTG 1204 chr17 ENST00000394620.1 CCL8 CCGGCAGGTGCAGTGTGACATTATTCTCGAGAATAATGTCACACTGCACCTGTTTTTG 1205 chr17 ENST00000394620.1 CCL8 CCGGTTGTACTGCTGTTGTTGAAATCTCGAGATTTCAACAACAGCAGTACAATTTTTG 1206 chr17 ENST00000394620.1 CCR1 CCGGATTCTGCTAAGACGACCAAATCTCGAGATTTGGTCGTCTTAGCAGAATTTTTTG 1207 chr3 ENST00000296140.3 CCR1 CCGGATCTGCTACACAGGGATTATACTCGAGTATAATCCCTGTGTAGCAGATTTTTTG 1208 chr3 ENST00000296140.3 CCR1 CCGGCCTCTGTACTCCTTGGTATTTCTCGAGAAATACCAAGGAGTACAGAGGTTTTTG 1209 chr3 ENST00000296140.3

CCR2 CCGGACGGTGCTCCCTGTCATAAATCTCGAGATTTATGACAGGGAGCACCGTTTTTTG 1210 chr3 ENST00000445132.2 CCR2 CCGGCTTCTGGACTCCCTATAATATCTCGAGATATTATAGGGAGTCCAGAAGTTTTTG 1211 chr3 ENST00000445132.2 CCR2 CCGGGCTGTATCACATCGGTTATTTCTCGAGAAATAACCGATGTGATACAGCTTTTTG 1212 chr3 ENST00000445132.2 CCR3 CCGGATACAGGAGGCTCCGAATTATCTCGAGATAATTCGGAGCCTCCTGTATTTTTTG 1213 chr3 ENST00000357422.2 CCR3 CCGGCCCAGAGGATACAGTATATAGCTCGAGCTATATACTGTATCCTCTGGGTTTTTG 1214 chr3 ENST00000357422.2 CCR3 CCGGTAGCAGCTCTTCCTGAATTTACTCGAGTAAATTCAGGAAGAGCTGCTATTTTTG 1215 chr3 ENST00000357422.2 CCR5 CCGGACTCTTGACAGGGCTCTATTTCTCGAGAAATAGAGCCCTGTCAAGAGTTTTTTG 1216 chr3 ENST00000292303.4 CCR5 CCGGCGAGCGAGCAAGCTCAGTTTACTCGAGTAAACTGAGCTTGCTCGCTCGTTTTTG 1217 chr3 ENST00000292303.4 CCR5 CCGGTCCATACAGTCAGTATCAATTCTCGAGAATTGATACTGACTGTATGGATTTTTG 1218 chr3 ENST00000292303.4 CCR6 CCGGGGTCTATGACAGACGTCTATCCTCGAGGATAGACGTCTGTCATAGACCTTTTTG 1219 chr6 ENST00000341935.9 CCR6 CCGGCGACTCCAGTGAAGATTATTTCTCGAGAAATAATCTTCACTGGAGTCGTTTTTG 1220 chr6 ENST00000341935.9 CCR6 CCGGTCGACTCCAGTGAAGATTATTCTCGAGAATAATCTTCACTGGAGTCGATTTTTG 1221 chr6 ENST00000341935.9 CCR7 CCGGGATGAGGTCACGGACGATTACCTCGAGGTAATCGTCCGTGACCTCATCTTTTTG 1222 chr17 ENST00000246657.2 CCR7 CCGGGCTGGTCGTGTTGACCTATATCTCGAGATATAGGTCAACACGACCAGCTTTTTG 1223 chr17 ENST00000246657.2 CCR7 CCGGCGTGTTGACCTATATCTATTTCTCGAGAAATAGATATAGGTCAACACGTTTTTG 1224 chr17 ENST00000246657.2 CD109 CCGGGCCGATCCTTACATAGATATTCTCGAGAATATCTATGTAAGGATCGGCTTTTTG 1225 chr6 ENST00000287097.5 CD109 CCGGCCCGGAGGAAATGTGACTATTCTCGAGAATAGTCACATTTCCTCCGGGTTTTTG 1226 chr6 ENST00000287097.5 CD109 CCGGCCGCTTATCATTTGAGACCAACTCGAGTTGGTCTCAAATGATAAGCGGTTTTTG 1227 chr6 ENST00000287097.5 CD27 CCGGCTTACCTTATGTCAGTGAGATCTCGAGATCTCACTGACATAAGGTAAGTTTTTG 1228 chr12 ENST00000266557.3 CD27 CCGGGCACTGTAACTCTGGTCTTCTCTCGAGAGAAGACCAGAGTTACAGTGCTTTTTG 1229 chr12 ENST00000266557.3 CD27 CCGGCCACCCACTTACCTTATGTCACTCGAGTGACATAAGGTAAGTGGGTGGTTTTTG 1230 chr12 ENST00000266557.3 CD27 CCGGGCCAGATGTGTGAGCCAGGAACTCGAGTTCCTGGCTCACACATCTGGCTTTTTG 1231 chr12 ENST00000266557.3 CD28 CCGGCCTCCAGAATTTGTATGTTAACTCGAGTTAACATACAAATTCTGGAGGTTTTTG 1232 ch2 ENST00000458610.6 CD28 CCGGCAACCTTAGCTGCAAGTATTCCTCGAGGAATACTTGCAGCTAAGGTTGTTTTTG 1233 ch2 ENST00000458610.6 CD28 CCGGTGGAGTCCTGGCTTGCTATAGCTCGAGCTATAGCAAGCCAGGACTCCATTTTTG 1234 ch2 ENST00000458610.6 CD28 CCGGCCTCCTCCTTACCTAGACAATCTCGAGATTGTCTAGGTAAGGAGGAGGTTTTTG 1235 ch2 ENST00000458610.6 CD36 CCGGAGAACCTATTGATGGATTAAACTCGAGTTTAATCCATCAATAGGTTCTTTTTTG 1236 chr7 ENST00000309881.11 CD36 CCGGGCCATAATCGACACATATAAACTCGAGTTTATATGTGTCGATTATGGCTTTTTG 1237 chr7 ENST00000309881.11 CD36 CCGGACGGCTGCAGGTCAACCTATTCTCGAGAATAGGTTGACCTGCAGCCGTTTTTTG 1238 chr7 ENST00000309881.11 CD4 CCGGCCTGATCATCAAGAATCTTAACTCGAGTTAAGATTCTTGATGATCAGGTTTTTG 1239 chr12 ENST00000011653.8 CD4 CCGGAGAGCGGATGTCTCAGATCAACTCGAGTTGATCTGAGACATCCGCTCTTTTTTG 1240 chr12 ENST00000011653.8 CD4 CCGGCCACTCGCCTTTACAGTTGAACTCGAGTTCAACTGTAAAGGCGAGTGGTTTTTG 1241 chr12 ENST00000011653.8 CD40LG CCGGGGGAAACAGCTGACCGTTAAACTCGAGTTTAACGGTCAGCTGTTTCCCTTTTTG 1242 chrX ENST00000370629.6 CD40LG CCGGTTCGAGTCAAGCTCCATTTATCTCGAGATAAATGGAGCTTGACTCGAATTTTTG 1243 chrX ENST00000370629.6 CD40LG CCGGTGACGCTGGGAGTCTTCATAACTCGAGTTATGAAGACTCCCAGCGTCATTTTTG 1244 chrX ENST00000370629.6 CD70 CCGGCCATCGTGATGGCATCTACATCTCGAGATGTAGATGCCATCACGATGGTTTTTG 1245 chr19 ENST00000245903.3 CD70 CCGGCAGCTACGTATCCATCGTGATCTCGAGATCACGATGGATACGTAGCTGTTTTTG 1246 chr19 ENST00000245903.3 CD70 CCGGCCAACCTCACTGGGACACTTTCTCGAGAAAGTGTCCCAGTGAGGTTGGTTTTTG 1247 chr19 ENST00000245903.3 CD74 CCGGCAAGTCGGAACAGCAGATAACCTCGAGGTTATCTGCTGTTCCGACTTGTTTTTG 1248 chr5 ENST00000009530.11 CD74 CCGGGAGAACCTGAGACACCTTAAGCTCGAGCTTAAGGTGTCTCAGGTTCTCTTTTTG 1249 chr5 ENST00000009530.11 CD74 CCGGCCACACAGCTACAGCTTTCTTCTCGAGAAGAAAGCTGTAGCTGTGTGGTTTTTG 1250 chr5 ENST00000009530.11 CD8A CCGGGCTGGACTTCGCCTGTGATATCTCGAGATATCACAGGCGAAGTCCAGCTTTTTG 1251 ch2 ENST00000409511.6 CD8A CCGGGTGTATTCATTCTCATGATTACTCGAGTAATCATGAGAATGAATACACTTTTTG 1252 ch2 ENST00000409511.6 CD8A CCGGCCAGAGACAGCTTGATCAAAGCTCGAGCTTTGATCAAGCTGTCTCTGGTTTTTG 1253 ch2 ENST00000409511.6 CD8A CCGGCCTTCTCCTGTCACTGGTTATCTCGAGATAACCAGTGACAGGAGAAGGTTTTTG 1254 ch2 ENST00000409511.6 CER1 CCGGGAGAAGATGCTGTCCAGATTTCTCGAGAAATCTGGACAGCATCTTCTCTTTTTG 1255 chr9 ENST00000380911.3 CER1 CCGGCCAGCCGATAGATGGAATGAACTCGAGTTCATTCCATCTATCGGCTGGTTTTTG 1256 chr9 ENST00000380911.3 CER1 CCGGCAAGAAATTCTGGCACCACTTCTCGAGAAGTGGTGCCAGAATTTCTTGTTTTTG 1257 chr9 ENST00000380911.3 CHRD CCGGACGTCCTGCAAAGTGTCCTTTCTCGAGAAAGGACACTTTGCAGGACGTTTTTTG 1258 chr3 ENST00000204604.5 CHRD CCGGACTGATCCAGAGCTGGAGAAACTCGAGTTTCTCCAGCTCTGGATCAGTTTTTTG 1259 chr3 ENST00000204604.5 CHRD CCGGCGGCTGCTGAAGGGATTCTATCTCGAGATAGAATCCCTTCAGCAGCCGTTTTTG 1260 chr3 ENST00000204604.5 CKLF CCGGCCTTTGCTTGTGTTTGCACTTCTCGAGAAGTGCAAACACAAGCAAAGGTTTTTG 1261 chr16 ENST00000264001.8 CKLF CCGGCCCTGAACCATATATTGTTATCTCGAGATAACAATATATGGTTCAGGGTTTTTG 1262 chr16 ENST00000264001.8 CKLF CCGGTGGATTTGAAGTCACCGTTATCTCGAGATAACGGTGACTTCAAATCCATTTTTG 1263 chr16 ENST00000264001.8 CLCF1 CCGGGAAACAAACATGGTGGCAATTCTCGAGAATTGCCACCATGTTTGTTTCTTTTTG 1264 chr11 ENST00000312438.7 CLCF1 CCGGCCACAGGATTTCCTGAAAGTTCTCGAGAACTTTCAGGAAATCCTGTGGTTTTTG 1265 chr11 ENST00000312438.7 CLCF1 CCGGCATGGTGGCAATTCTACACAACTCGAGTTGTGTAGAATTGCCACCATGTTTTTG 1266 chr11 ENST00000312438.7 CMTM1 CCGGCACCACTTGCTGACCTATTTACTCGAGTAAATAGGTCAGCAAGTGGTGTTTTTG 1267 chr16 ENST00000379500.6 CMTM1 CCGGGACCTATTTACATTGGCCCTTCTCGAGAAGGGCCAATGTAAATAGGTCTTTTTG 1268 chr16 ENST00000379500.6 CMTM1 CCGGGCTGTGTTCCTTTCAGTAGTTCTCGAGAACTACTGAAAGGAACACAGCTTTTTG 1269 chr16 ENST00000379500.6 CMTM2 CCGGGTAAGGAGCCATCGGACAAACCTCGAGGTTTGTCCGATGGCTCCTTACTTTTTG 1270 chr16 ENST00000268595.2 CMTM2 CCGGCTTACTTGCTGTGATCCTTATCTCGAGATAAGGATCACAGCAAGTAAGTTTTTG 1271 chr16 ENST00000268595.2 CMTM2 CCGGCATAAGGAGCCATCGGACAAACTCGAGTTTGTCCGATGGCTCCTTATGTTTTTG 1272 chr16 ENST00000268595.2 CMTM3 CCGGCATCGTGTTTGCAACTGATTTCTCGAGAAATCAGTTGCAAACACGATGTTTTTG 1273 chr16 ENST00000361909.8 CMTM3 CCGGGCTTCTTAACAGATGGCATTTCTCGAGAAATGCCATCTGTTAAGAAGCTTTTTG 1274 chr16 ENST00000361909.8 CMTM3 CCGGGCTTCTTAACAGATGGCATTTCTCGAGAAATGCCATCTGTTAAGAAGCTTTTTG 1275 chr16 ENST00000361909.8 CMTM4 CCGGCAACTGGAATCTGACAGATTTCTCGAGAAATCTGTCAGATTCCAGTTGTTTTTG 1276 chr16 ENST00000394106.6 CMTM4 CCGGGACTGGCGTCTTGCTGATTATCTCGAGATAATCAGCAAGACGCCAGTCTTTTTG 1277 chr16 ENST00000394106.6 CMTM4 CCGGGCAGAAATTGCTGCCGTGATACTCGAGTATCACGGCAGCAATTTCTGCTTTTTG 1278 chr16 ENST00000394106.6 CMTM5 CCGGCAAGATCTACCGGACTGAGATCTCGAGATCTCAGTCCGGTAGATCTTGTTTTTG 1279 chr14 ENST00000359320.7 CMTM5 CCGGCCTGACCCTCATCATCTTCATCTCGAGATGAAGATGATGAGGGTCAGGTTTTTG 1280 chr14 ENST00000359320.7 CMTM5 CCGGCTTCCTCTATGCCACCCAGTACTCGAGTACTGGGTGGCATAGAGGAAGTTTTTG 1281 chr14 ENST00000359320.7 CMTM6 CCGGGCCCTCACTGAGCCACTTAATCTCGAGATTAAGTGGCTCAGTGAGGGCTTTTTG 1282 chr3 ENST00000205636.3 CMTM6 CCGGCCCAAGACAGTGAAAGTAATTCTCGAGAATTACTTTCACTGTCTTGGGTTTTTG 1283 chr3 ENST00000205636.3 CMTM6 CCGGCCCAAGACAGTGAAAGTAATTCTCGAGAATTACTTTCACTGTCTTGGGTTTTTG 1284 chr3 ENST00000205636.3 CMTM7 CCGGCTGCTGAAAGTGGCGCAAATGCTCGAGCATTTGCGCCACTTTCAGCAGTTTTTG 1285 chr3 ENST00000334983.9 CMTM7 CCGGCAAAGCCCTGTCCTAATTTATCTCGAGATAAATTAGGACAGGGCTTTGTTTTTG 1286 chr3 ENST00000334983.9 CMTM7 CCGGCCTGTCGATCTTTGGTTTCATCTCGAGATGAAACCAAAGATCGACAGGTTTTTG 1287 chr3 ENST00000334983.9 CMTM8 CCGGTGCTGGTATGGACGCTTATTGCTCGAGCAATAAGCGTCCATACCAGCATTTTTG 1288 chr3 ENST00000307526.3 CMTM8 CCGGGCAAAGTGTTGTAGCTTATAACTCGAGTTATAAGCTACAACACTTTGCTTTTTG 1289 chr3 ENST00000307526.3 CMTM8 CCGGATATTCCCAGAGAATTGTATTCTCGAGAATACAATTCTCTGGGAATATTTTTTG 1290 chr3 ENST00000307526.3 CNTF CCGGGTAACCTCTACAGGCATTTAACTCGAGTTAAATGCCTGTAGAGGTTACTTTTTG 1291 chr11 ENST00000361987.5 CNTF CCGGGTTGAAGGACTACAGGTATTTCTCGAGAAATACCTGTAGTCCTTCAACTTTTTG 1292 chr11 ENST00000361987.5 CNTF CCGGGGTGACTTCCATCAAGCTATACTCGAGTATAGCTTGATGGAAGTCACCTTTTTG 1293 chr11 ENST00000361987.5

CNTFR CCGGCATTCTCTTCAGACACAATTTCTCGAGAAATTGTGTCTGAAGAGAATGTTTTTG 1294 chr9 ENST00000351266.8 CNTFR CCGGGCATTCTCTTCAGACACAATTCTCGAGAATTGTGTCTGAAGAGAATGCTTTTTG 1295 chr9 ENST00000351266.8 CNTFR CCGGGCCGGGAAGGAGTACATTATCCTCGAGGATAATGTACTCCTTCCCGGCTTTTTG 1296 chr9 ENST00000351266.8 COPS5 CCGGCTAAGGATCACCATTACTTTACTCGAGTAAAGTAATGGTGATCCTTAGTTTTTG 1297 chr8 ENST00000357849.8 COPS5 CCGGCCAGACTATTCCACTTAATAACTCGAGTTATTAAGTGGAATAGTCTGGTTTTTG 1298 chr8 ENST00000357849.8 COPS5 CCGGCAGTCTCTGAGAAGTACTTTACTCGAGTAAAGTACTTCTCAGAGACTGTTTTTG 1299 chr8 ENST00000357849.8 CRLF1 CCGGCGATGTACTCACGCTGGATATCTCGAGATATCCAGCGTGAGTACATCGTTTTTG 1300 chr19 ENST00000392386.7 CRLF1 CCGGCGATGTACTCACGCTGGATATCTCGAGATATCCAGCGTGAGTACATCGTTTTTG 1301 chr19 ENST00000392386.7 CRLF1 CCGGCCCAGAGAAACCCGTCAACATCTCGAGATGTTGACGGGTTTCTCTGGGTTTTTG 1302 chr19 ENST00000392386.7 CSF1 CCGGTCTCCTGGTACAAGACATAATCTCGAGATTATGTCTTGTACCAGGAGATTTTTG 1303 chr1 ENST00000329608.10 CSF1 CCGGGTCGGCCTGATTTCCCGTAAACTCGAGTTTACGGGAAATCAGGCCGACTTTTTG 1304 chr1 ENST00000329608.10 CSF1 CCGGTTGACAAGGACTGGAATATTTCTCGAGAAATATTCCAGTCCTTGTCAATTTTTG 1305 chr1 ENST00000329608.10 CSF1R CCGGGTGAACAGCAAGTTCTATAAACTCGAGTTTATAGAACTTGCTGTTCACTTTTTG 1306 chr5 ENST00000286301.7 CSF1R CCGGACAGGAGAGAGCGGGACTATACTCGAGTATAGTCCCGCTCTCTCCTGTTTTTTG 1307 chr5 ENST00000286301.7 CSF1R CCGGGCTGCTATTGTACAAGTATAACTCGAGTTATACTTGTACAATAGCAGCTTTTTG 1308 chr5 ENST00000286301.7 CSF2 CCGGGGAGCTGCTCTCTCATGAAACCTCGAGGTTTCATGAGAGAGCAGCTCCTTTTTG 1309 chr5 ENST00000296871.3 CSF2 CCGGCCCAGATTATCACCTTTGAAACTCGAGTTTCAAAGGTGATAATCTGGGTTTTTG 1310 chr5 ENST00000296871.3 CSF2 CCGGGAAGTCATCTCAGAAATGTTTCTCGAGAAACATTTCTGAGATGACTTCTTTTTG 1311 chr5 ENST00000296871.3 CSF3 CCGGGTCTATTTAAGCCTCATATTTCTCGAGAAATATGAGGCTTAAATAGACTTTTTG 1312 chr17 ENST00000225474.6 CSF3 CCGGGATAGGTAAATACCAAGTATTCTCGAGAATACTTGGTATTTACCTATCTTTTTG 1313 chr17 ENST00000225474.6 CSF3 CCGGGCTTAGAGCAAGTGAGGAAGACTCGAGTCTTCCTCACTTGCTCTAAGCTTTTTG 1314 chr17 ENST00000225474.6 CSF3R CCGGCAGCCAGGCCTGCACATAAATCTCGAGATTTATGTGCAGGCCTGGCTGTTTTTG 1315 chr1 ENST00000361632.8 CSF3R CCGGCTATGCCTACTCTCAAGAAATCTCGAGATTTCTTGAGAGTAGGCATAGTTTTTG 1316 chr1 ENST00000361632.8 CSF3R CCGGCCAGCTTCACTCTGAAGAGTTCTCGAGAACTCTTCAGAGTGAAGCTGGTTTTTG 1317 chr1 ENST00000361632.8 CTF1 CCGGGAGCAGCTGCTCCAGGAATATCTCGAGATATTCCTGGAGCAGCTGCTCTTTTTG 1318 chr16 ENST00000279804.2 CTF1 CCGGGTCTCTCCTTCCGCTTCTTTGCTCGAGCAAAGAAGCGGAAGGAGAGACTTTTTG 1319 chr16 ENST00000279804.2 CTF1 CCGGTGTCTGTCTGTCTGCTCTTAGCTCGAGCTAAGAGCAGACAGACAGACATTTTTG 1320 chr16 ENST00000279804.2 CX3CL1 CCGGCCCGGAGCTGTGGTAGTAATTCTCGAGAATTACTACCACAGCTCCGGGTTTTTG 1321 chr16 ENST00000006053.6 CX3CL1 CCGGGCTGCTGCCCTAACTCGAAATCTCGAGATTTCGAGTTAGGGCAGCAGCTTTTTG 1322 chr16 ENST00000006053.6 CX3CL1 CCGGCGGTGTGACGAAATGCAACATCTCGAGATGTTGCATTTCGTCACACCGTTTTTG 1323 chr16 ENST00000006053.6 CX3CR1 CCGGTGGCCTGTGTCTAGTTGTTTGCTCGAGCAAACAACTAGACACAGGCCATTTTTG 1324 chr3 ENST00000399220.2 CX3CR1 CCGGTGGGATCCCTCATCCTCATACCTCGAGGTATGAGGATGAGGGATCCCATTTTTG 1325 chr3 ENST00000399220.2 CX3CR1 CCGGGCTTTGCTCATCCACTATCAACTCGAGTTGATAGTGGATGAGCAAAGCTTTTTG 1326 chr3 ENST00000399220.2 CXCL1 CCGGACCTGCACACTGTCCTATTATCTCGAGATAATAGGACAGTGTGCAGGTTTTTTG 1327 chr4 ENST00000395761.3 CXCL1 CCGGAGATGCTGAACAGTGACAAATCTCGAGATTTGTCACTGTTCAGCATCTTTTTTG 1328 chr4 ENST00000395761.3 CXCL1 CCGGGTTCTCCAGTCATTATGTTAACTCGAGTTAACATAATGACTGGAGAACTTTTTG 1329 chr4 ENST00000395761.3 CXCL10 CCGGGTATATGTCAAGCCATAATTGCTCGAGCAATTATGGCTTGACATATACTTTTTG 1330 chr4 ENST00000306602.2 CXCL10 CCGGACTCTACCCTGGCACTATAATCTCGAGATTATAGTGCCAGGGTAGAGTTTTTTG 1331 chr4 ENST00000306602.2 CXCL10 CCGGCCTGTTAATCCAAGGTCTTTACTCGAGTAAAGACCTTGGATTAACAGGTTTTTG 1332 chr4 ENST00000306602.2 CXCL11 CCGGGCTGGTTACCATCGGAGTTTACTCGAGTAAACTCCGATGGTAACCAGCTTTTTG 1333 chr4 ENST00000306621.7 CXCL11 CCGGGCAGTGAAAGTGGCAGATATTCTCGAGAATATCTGCCACTTTCACTGCTTTTTG 1334 chr4 ENST00000306621.7 CXCL11 CCGGGAAGCAAGCAAGGCTTATAATCTCGAGATTATAAGCCTTGCTTGCTTCTTTTTG 1335 chr4 ENST00000306621.7 CXCL12 CCGGGCTTAGACTAAGGCCATTATTCTCGAGAATAATGGCCTTAGTCTAAGCTTTTTG 1336 chr10 ENST00000343575.10 CXCL12 CCGGCTCTCACTATACCAGTATAATCTCGAGATTATACTGGTATAGTGAGAGTTTTTG 1337 chr10 ENST00000343575.10 CXCL12 CCGGCAAACTGTGCCCTTCAGATTGCTCGAGCAATCTGAAGGGCACAGTTTGTTTTTG 1338 chr10 ENST00000343575.10 CXCL13 CCGGGATTCCCTGATGCTGATATTTCTCGAGAAATATCAGCATCAGGGAATCTTTTTG 1339 chr4 ENST00000286758.4 CXCL13 CCGGAGGAATCCATGTAGTAGATATCTCGAGATATCTACTACATGGATTCCTTTTTTG 1340 chr4 ENST00000286758.4 CXCL13 CCGGAGGTGTTCTGGAGGTCTATTACTCGAGTAATAGACCTCCAGAACACCTTTTTTG 1341 chr4 ENST00000286758.4 CXCL14 CCGGATTTGTCCATACGTCACTATACTCGAGTATAGTGACGTATGGACAAATTTTTTG 1342 chr5 ENST00000337225.5 CXCL14 CCGGCAAAGGACTTTGCAGATTAAACTCGAGTTTAATCTGCAAAGTCCTTTGTTTTTG 1343 chr5 ENST00000337225.5 CXCL14 CCGGGCGCAGGGTCTACGAAGAATACTCGAGTATTCTTCGTAGACCCTGCGCTTTTTG 1344 chr5 ENST00000337225.5 CXCL16 CCGGACATCCAGCCTACACGTATTTCTCGAGAAATACGTGTAGGCTGGATGTTTTTTG 1345 chr17 ENST00000293778.10 CXCL16 CCGGTCTGAAGGTGCGAGGATTATACTCGAGTATAATCCTCGCACCTTCAGATTTTTG 1346 chr17 ENST00000293778.10 CXCL16 CCGGTCCAGATCTGCCGGTTCATTACTCGAGTAATGAACCGGCAGATCTGGATTTTTG 1347 chr17 ENST00000293778.10 CXCL17 CCGGGCGCCCACTCTTCCAATTAAACTCGAGTTTAATTGGAAGAGTGGGCGCTTTTTG 1348 chr19 ENST00000601181.5 CXCL17 CCGGTCCAGAGCCTGCCAGCAATTTCTCGAGAAATTGCTGGCAGGCTCTGGATTTTTG 1349 chr19 ENST00000601181.5 CXCL17 CCGGAGAATGTGAGTGCAAAGATTGCTCGAGCAATCTTTGCACTCACATTCTTTTTTG 1350 chr19 ENST00000601181.5 CXCL2 CCGGCTTGCACACTCTCCCATTATACTCGAGTATAATGGGAGAGTGTGCAAGTTTTTG 1351 chr4 ENST00000508487.2 CXCL2 CCGGGCAGATATTCTCTAGTCATTTCTCGAGAAATGACTAGAGAATATCTGCTTTTTG 1352 chr4 ENST00000508487.2 CXCL2 CCGGATTTCTTCGTGATGACATATCCTCGAGGATATGTCATCACGAAGAAATTTTTTG 1353 chr4 ENST00000508487.2 CXCL3 CCGGTTACGAGGGTTCTACTTATTTCTCGAGAAATAAGTAGAACCCTCGTAATTTTTG 1354 chr4 ENST00000296026.4 CXCL3 CCGGATTTAGTGGGAGACCATAATGCTCGAGCATTATGGTCTCCCACTAAATTTTTTG 1355 chr4 ENST00000296026.4 CXCL3 CCGGACTGACAGGAGAGAAGTAAGACTCGAGTCTTACTTCTCTCCTGTCAGTTTTTTG 1356 chr4 ENST00000296026.4 CXCL5 CCGGTGAATTGTAGGTGACTATTATCTCGAGATAATAGTCACCTACAATTCATTTTTG 1357 chr4 ENST00000296027.4 CXCL5 CCGGCAGACCACGCAAGGAGTTCATCTCGAGATGAACTCCTTGCGTGGTCTGTTTTTG 1358 chr4 ENST00000296027.4 CXCL5 CCGGCGGGAAGGAAATTTGTCTTGACTCGAGTCAAGACAAATTTCCTTCCCGTTTTTG 1359 chr4 ENST00000296027.4 CXCL6 CCGGTTTACCCTAGGATGCTATTTACTCGAGTAAATAGCATCCTAGGGTAAATTTTTG 1360 chr4 ENST00000226317.9 CXCL6 CCGGGTTGCACTTGTTTACGCGTTACTCGAGTAACGCGTAAACAAGTGCAACTTTTTG 1361 chr4 ENST00000226317.9 CXCL6 CCGGGCTGTGGATTTCGTATGGAAACTCGAGTTTCCATACGAAATCCACAGCTTTTTG 1362 chr4 ENST00000226317.9 CXCL8 CCGGTGCGCCAACACAGAAATTATTCTCGAGAATAATTTCTGTGTTGGCGCATTTTTG 1363 chr4 ENST00000307407.7 CXCL8 CCGGCAAGAGAATATCCGAACTTTACTCGAGTAAAGTTCGGATATTCTCTTGTTTTTG 1364 chr4 ENST00000307407.7 CXCL8 CCGGTGCACGGGAGAATATACAAATCTCGAGATTTGTATATTCTCCCGTGCATTTTTG 1365 chr4 ENST00000307407.7 CXCL9 CCGGCCAAAGGAGGATGGCATATAACTCGAGTTATATGCCATCCTCCTTTGGTTTTTG 1366 chr4 ENST00000264888.5 CXCL9 CCGGCCAAACGTTAAGAATTGTTAACTCGAGTTAACAATTCTTAACGTTTGGTTTTTG 1367 chr4 ENST00000264888.5 CXCL9 CCGGGATGTGAAGGAACTGATTAAACTCGAGTTTAATCAGTTCCTTCACATCTTTTTG 1368 chr4 ENST00000264888.5 CXCR1 CCGGCTTGGCACGTCATCGTGTTACCTCGAGGTAACACGATGACGTGCCAAGTTTTTG 1369 chr2 ENST00000295683.2 CXCR1 CCGGACCCACTAACTGGCTAATTAGCTCGAGCTAATTAGCCAGTTAGTGGGTTTTTTG 1370 chr2 ENST00000295683.2 CXCR1 CCGGGAGACACTCAACAAGTATGTTCTCGAGAACATACTTGTTGAGTGTCTCTTTTTG 1371 chr2 ENST00000295683.2 CXCR2 CCGGGAAGCGCTACTTGGTCAAATTCTCGAGAATTTGACCAAGTAGCGCTTCTTTTTG 1372 chr2 ENST00000318507.6 CXCR2 CCGGGCCACTAAATTGACACTTAAACTCGAGTTTAAGTGTCAATTTAGTGGCTTTTTG 1373 chr2 ENST00000318507.6 CXCR2 CCGGCCCTGGAAATCAACAAGTATTCTCGAGAATACTTGTTGATTTCCAGGGTTTTTG 1374 chr2 ENST00000318507.6 CXCR3 CCGGCCTTCTCATTTGGAAACTAAACTCGAGTTTAGTTTCCAAATGAGAAGGTTTTTG 1375 chrX ENST00000373693.3 CXCR3 CCGGCGCTACCTGAACATAGTTCATCTCGAGATGAACTATGTTCAGGTAGCGTTTTTG 1376 chrX ENST00000373693.3 CXCR3 CCGGGAGTACAAGGCATGGCGTAGACTCGAGTCTACGCCATGCCTTGTACTCTTTTTG 1377 chrX

ENST00000373693.3 CXCR4 CCGGCTATTCCCGACTTCATCTTTGCTCGAGCAAAGATGAAGTCGGGAATAGTTTTTG 1378 chr2 ENST00000409817.1 CXCR4 CCGGGCGTGTAGTGAATCACGTAAACTCGAGTTTACGTGATTCACTACACGCTTTTTG 1379 chr2 ENST00000409817.1 CXCR4 CCGGCCTGTTCTTAAGACGTGATTTCTCGAGAAATCACGTCTTAAGAACAGGTTTTTG 1380 chr2 ENST00000409817.1 CXCR6 CCGGGCTTGCTCATCTGGGTGATATCTCGAGATATCACCCAGATGAGCAAGCTTTTTG 1381 chr3 ENST00000304552.4 CXCR6 CCGGTACTGGGCATCTACACTATTACTCGAGTAATAGTGTAGATGCCCAGTATTTTTG 1382 chr3 ENST00000304552.4 CXCR6 CCGGTTATCTATGGCAATGTCTTTACTCGAGTAAAGACATTGCCATAGATAATTTTTG 1383 chr3 ENST00000304552.4 EBI3 CCGGTGAACTGTCACTGTGAGATATCTCGAGATATCTCACAGTGACAGTTCATTTTTG 1384 chr19 ENST00000221847.5 EBI3 CCGGATGTACTACTCTCTCCTTTACCTCGAGGTAAAGGAGAGAGTAGTACATTTTTTG 1385 chr19 ENST00000221847.5 EBI3 CCGGGCCTTTCATAACAGAGCACATCTCGAGATGTGCTCTGTTATGAAAGGCTTTTTG 1386 chr19 ENST00000221847.5 EDN1 CCGGCCATGAGAAACAGCGTCAAATCTCGAGATTTGACGCTGTTTCTCATGGTTTTTG 1387 chr6 ENST00000379375.5 EDN1 CCGGGCTCGTCCCTGATGGATAAAGCTCGAGCTTTATCCATCAGGGACGAGCTTTTTG 1388 chr6 ENST00000379375.5 EDN1 CCGGAGACAAGAAGTGCTGGAATTTCTCGAGAAATTCCAGCACTTCTTGTCTTTTTTG 1389 chr6 ENST00000379375.5 ELANE CCGGGCACTGCGTGGCGAATGTAAACTCGAGTTTACATTCGCCACGCAGTGCTTTTTG 1390 chr19 ENST00000263621.1 ELANE CCGGTGCTCAACGACATCGTGATTCCTCGAGGAATCACGATGTCGTTGAGCATTTTTG 1391 chr19 ENST00000263621.1 ELANE CCGGCAACGGGCTAATCCACGGAATCTCGAGATTCCGTGGATTAGCCCGTTGTTTTTG 1392 chr19 ENST00000263621.1 ENG CCGGGCAGGTGTCAGCAAGTATGATCTCGAGATCATACTTGCTGACACCTGCTTTTTG 1393 chr9 ENST00000344849.4 ENG CCGGGCAGGTGTCAGCAAGTATGATCTCGAGATCATACTTGCTGACACCTGCTTTTTG 1394 chr9 ENST00000344849.4 ENG CCGGGTCTTGCAGAAACAGTCCATTCTCGAGAATGGACTGTTTCTGCAAGACTTTTTG 1395 chr9 ENST00000344849.4 EPO CCGGCCCAGACACCAAAGTTAATTTCTCGAGAAATTAACTTTGGTGTCTGGGTTTTTG 1396 chr7 ENST00000252723.2 EPO CCGGTGCAGCTGCATGTGGATAAAGCTCGAGCTTTATCCACATGCAGCTGCATTTTTG 1397 chr7 ENST00000252723.2 EPO CCGGAGAGCAACTCTGAGATCTAAGCTCGAGCTTAGATCTCAGAGTTGCTCTTTTTTG 1398 chr7 ENST00000252723.2 FAM3B CCGGTTGGAACTCCCTTCCGAAATTCTCGAGAATTTCGGAAGGGAGTTCCAATTTTTG 1399 chr21 ENST00000357985.6 FAM3B CCGGTAAATCCAACAGCCCATATTTCTCGAGAAATATGGGCTGTTGGATTTATTTTTG 1400 chr21 ENST00000357985.6 FAM3B CCGGTCAGGTCTAGCTGGGTATTTACTCGAGTAAATACCCAGCTAGACCTGATTTTTG 1401 chr21 ENST00000357985.6 FAM3C CCGGCTTGGTGTGTGCATGAGTATTCTCGAGAATACTCATGCACACACCAAGTTTTTG 1402 chr7 ENST00000359943.7 FAM3C CCGGGAGGAGATGTGGCACCATTTACTCGAGTAAATGGTGCCACATCTCCTCTTTTTG 1403 chr7 ENST00000359943.7 FAM3C CCGGGCCATACAAGATGGAACAATACTCGAGTATTGTTCCATCTTGTATGGCTTTTTG 1404 chr7 ENST00000359943.7 FAM3D CCGGCACCTAGTGAAATTCCTTAAACTCGAGTTTAAGGAATTTCACTAGGTGTTTTTG 1405 chr3 ENST00000358781.6 FAM3D CCGGCATGTACTCTGGAGATGTTATCTCGAGATAACATCTCCAGAGTACATGTTTTTG 1406 chr3 ENST00000358781.6 FAM3D CCGGCAATGTGGGCAGAGGCCTAAACTCGAGTTTAGGCCTCTGCCCACATTGTTTTTG 1407 chr3 ENST00000358781.6 FAS CCGGGCGTATGACACATTGATTAAACTCGAGTTTAATCAATGTGTCATACGCTTTTTG 1408 chr10 ENST00000355740.6 FAS CCGGCCTGAAACAGTGGCAATAAATCTCGAGATTTATTGCCACTGTTTCAGGTTTTTG 1409 chr10 ENST00000355740.6 FAS CCGGCTATCATCCTCAAGGACATTACTCGAGTAATGTCCTTGAGGATGATAGTTTTTG 1410 chr10 ENST00000355740.6 FASLG CCGGGACTAGAGGCTTGCATAATAACTCGAGTTATTATGCAAGCCTCTAGTCTTTTTG 1411 chr1 ENST00000367721.2 FASLG CCGGACTGGGCTGTACTTTGTATATCTCGAGATATACAAAGTACAGCCCAGTTTTTTG 1412 chr1 ENST00000367721.2 FASLG CCGGTGAGCTCTCTCTGGTCAATTTCTCGAGAAATTGACCAGAGAGAGCTCATTTTTG 1413 chr1 ENST00000367721.2 FGF2 CCGGGAAACGAACTGGGCAGTATAACTCGAGTTATACTGCCCAGTTCGTTTCTTTTTG 1414 chr4 ENST00000608478.1 FGF2 CCGGTATAGCTCAGTTTGGATAATTCTCGAGAATTATCCAAACTGAGCTATATTTTTG 1415 chr4 ENST00000608478.1 FGF2 CCGGTGAACGATTGGAATCTAATAACTCGAGTTATTAGATTCCAATCGTTCATTTTTG 1416 chr4 ENST00000608478.1 FLT3LG CCGGCTGTCTGACTACCTGCTTCAACTCGAGTTGAAGCAGGTAGTCAGACAGTTTTTG 1417 chr19 ENST00000594009.5 FLT3LG CCGGTCCTCCGACTTCGCTGTCAAACTCGAGTTTGACAGCGAAGTCGGAGGATTTTTG 1418 chr19 ENST00000594009.5 FLT3LG CCGGGCTTCGTCCAGACCAACATCTCTCGAGAGATGTTGGTCTGGACGAAGCTTTTTG 1419 chr19 ENST00000594009.5 FOXP3 CCGGAGCTGGAGTTCCGCAAGAAACCTCGAGGTTTCTTGCGGAACTCCAGCTTTTTTG 1420 chrX ENST00000376207.8 FOXP3 CCGGTCCTACCCACTGCTGGCAAATCTCGAGATTTGCCAGCAGTGGGTAGGATTTTTG 1421 chrX ENST00000376207.8 FOXP3 CCGGTGTCCCTCACTCAACACAAACCTCGAGGTTTGTGTTGAGTGAGGGACATTTTTG 1422 chrX ENST00000376207.8 FOXP3 CCGGCACACGCATGTTTGCCTTCTTCTCGAGAAGAAGGCAAACATGCGTGTGTTTTTG 1423 chrX ENST00000376207.8 FZD4 CCGGCGTGTGTGATTGCCTGTTATTCTCGAGAATAACAGGCAATCACACACGTTTTTG 1424 chr11 ENST00000531380.1 FZD4 CCGGTCTCAGTATGTGCTATAATATCTCGAGATATTATAGCACATACTGAGATTTTTG 1425 chr11 ENST00000531380.1 FZD4 CCGGTTCTCAGTATGTGCTATAATACTCGAGTATTATAGCACATACTGAGAATTTTTG 1426 chr11 ENST00000531380.1 GATA3 CCGGAGCCTAAACGCGATGGATATACTCGAGTATATCCATCGCGTTTAGGCTTTTTTG 1427 chr10 ENST00000346208.4 GATA3 CCGGCCCAAGAACAGCTCGTTTAACCTCGAGGTTAAACGAGCTGTTCTTGGGTTTTTG 1428 chr10 ENST00000346208.4 GATA3 CCGGGCCAAGAAGTTTAAGGAATATCTCGAGATATTCCTTAAACTTCTTGGCTTTTTG 1429 chr10 ENST00000346208.4 GATA3 CCGGCCCTGTAATTGTTGTTTGTATCTCGAGATACAAACAACAATTACAGGGTTTTTG 1430 chr10 ENST00000346208.4 GBP1 CCGGCCAGATGAGTACCTGACATACCTCGAGGTATGTCAGGTACTCATCTGGTTTTTG 1431 chr1 ENST00000370473.4 GBP1 CCGGCGACGAAAGGCATGTACCATACTCGAGTATGGTACATGCCTTTCGTCGTTTTTG 1432 chr1 ENST00000370473.4 GBP1 CCGGCGACGAAAGGCATGTACCATACTCGAGTATGGTACATGCCTTTCGTCGTTTTTG 1433 chr1 ENST00000370473.4 GDF1 CCGGGTTCACCAAGCTCAACATTTACTCGAGTAAATGTTGAGCTTGGTGAACTTTTTG 1434 chr19 ENST00000247005.7 GDF1 CCGGGAGTTCACCAAGCTCAACATTCTCGAGAATGTTGAGCTTGGTGAACTCTTTTTG 1435 chr19 ENST00000247005.7 GDF1 CCGGCCCTTATGAACCTCTACTGGTCTCGAGACCAGTAGAGGTTCATAAGGGTTTTTG 1436 chr19 ENST00000247005.7 GDF10 CCGGCAGGATAATCGTGGTGTAAATCTCGAGATTTACACCACGATTATCCTGTTTTTG 1437 chr10 ENST00000580279.1 GDF10 CCGGCGACCAGAAGGCCGTGTATTTCTCGAGAAATACACGGCCTTCTGGTCGTTTTTG 1438 chr10 ENST00000580279.1 GDF10 CCGGCTGTCCGCCAGTGCATCATTACTCGAGTAATGATGCACTGGCGGACAGTTTTTG 1439 chr10 ENST00000580279.1 GDF11 CCGGCCTGCAGATCTTGCGACTAAACTCGAGTTTAGTCGCAAGATCTGCAGGTTTTTG 1440 chr12 ENST00000257868.9 GDF11 CCGGGATCGCTGTGGCTGCTCTTAACTCGAGTTAAGAGCAGCCACAGCGATCTTTTTG 1441 chr12 ENST00000257868.9 GDF11 CCGGGAGATGTAGAGACAGTGATAGCTCGAGCTATCACTGTCTCTACATCTCTTTTTG 1442 chr12 ENST00000257868.9 GDF15 CCGGAGACTCCAGATTCCGAGAGTTCTCGAGAACTCTCGGAATCTGGAGTCTTTTTTG 1443 chr19 ENST00000252809.3 GDF15 CCGGGCTCCAGACCTATGATGACTTCTCGAGAAGTCATCATAGGTCTGGAGCTTTTTG 1444 chr19 ENST00000252809.3 GDF15 CCGGAGAGCTGGGAAGATTCGAACACTCGAGTGTTCGAATCTTCCCAGCTCTTTTTTG 1445 chr19 ENST00000252809.3 GDF2 CCGGCAACAGGTACACGTCCGATAACTCGAGTTATCGGACGTGTACCTGTTGTTTTTG 1446 chr10 ENST00000581492.2 GDF2 CCGGTGAAAGGAAGCGTGGTCATTTCTCGAGAAATGACCACGCTTCCTTTCATTTTTG 1447 chr10 ENST00000581492.2 GDF2 CCGGTATGAAGCCTACGAGTGTAAGCTCGAGCTTACACTCGTAGGCTTCATATTTTTG 1448 chr10 ENST00000581492.2 GDF3 CCGGACCGTCACCAGCTATTCATTACTCGAGTAATGAATAGCTGGTGACGGTTTTTTG 1449 chr12 ENST00000329913.3 GDF3 CCGGCTCTCAACAGCTCCAATTATGCTCGAGCATAATTGGAGCTGTTGAGAGTTTTTG 1450 chr12 ENST00000329913.3 GDF3 CCGGTTGGGCCAGGCAGTCCAATTTCTCGAGAAATTGGACTGCCTGGCCCAATTTTTG 1451 chr12 ENST00000329913.3 GDF5 CCGGCAACACCATCACCAGCTTTATCTCGAGATAAAGCTGGTGATGGTGTTGTTTTTG 1452 chr20 ENST00000374369.7 GDF5 CCGGATGAGACTCAGCCCACCATTTCTCGAGAAATGGTGGGCTGAGTCTCATTTTTTG 1453 chr20 ENST00000374369.7 GDF5 CCGGTGAGTGTGACTTGGGCTAAAGCTCGAGCTTTAGCCCAAGTCACACTCATTTTTG 1454 chr20 ENST00000374369.7 GDF6 CCGGGACTCCCATCAGCATTCTATACTCGAGTATAGAATGCTGATGGGAGTCTTTTTG 1455 chr8 ENST00000287020.6 GDF6 CCGGCGAGTACATGCTGTCAATCTACTCGAGTAGATTGACAGCATGTACTCGTTTTTG 1456 chr8 ENST00000287020.6 GDF6 CCGGCAGTCTTCCAAGTCGGCTAATCTCGAGATTAGCCGACTTGGAAGACTGTTTTTG 1457 chr8 ENST00000287020.6 GDF7 CCGGGCAGAGGAAAGAGAGCTTATTCTCGAGAATAAGCTCTCTTTCCTCTGCTTTTTG 1458 chr2 ENST00000272224.4 GDF7 CCGGGTTCGACGTGTCCAGCCTTAACTCGAGTTAAGGCTGGACACGTCGAACTTTTTG 1459 chr2 ENST00000272224.4 GDF7 CCGGCCACTTCATGATGTCGCTTTACTCGAGTAAAGCGACATCATGAAGTGGTTTTTG 1460 chr2 ENST00000272224.4

GDF9 CCGGGATGGCTCAATTGCCTATAAACTCGAGTTTATAGGCAATTGAGCCATCTTTTTG 1461 chr5 ENST00000378673.2 GDF9 CCGGCCATCAGTGGAACTGCTATTTCTCGAGAAATAGCAGTTCCACTGATGGTTTTTG 1462 chr5 ENST00000378673.2 GDF9 CCGGGAGTGAATACTTCAGACAATTCTCGAGAATTGTCTGAAGTATTCACTCTTTTTG 1463 chr5 ENST00000378673.2 GPI CCGGCGTCTGGTATGTCTCCAACATCTCGAGATGTTGGAGACATACCAGACGTTTTTG 1464 chr19 ENST00000356487.9 GPI CCGGCGTCTGGTATGTCTCCAACATCTCGAGATGTTGGAGACATACCAGACGTTTTTG 1465 chr19 ENST00000356487.9 GPI CCGGGCGGATGTTCAATGGTGAGAACTCGAGTTCTCACCATTGAACATCCGCTTTTTG 1466 chr19 ENST00000356487.9 GREM1 CCGGGCAGTGTCGTTGCATATCCATCTCGAGATGGATATGCAACGACACTGCTTTTTG 1467 chr15 ENST00000622074.1 GREM1 CCGGACAGCCACCTACCAAGAAGAACTCGAGTTCTTCTTGGTAGGTGGCTGTTTTTTG 1468 chr15 ENST00000622074.1 GREM1 CCGGCAACAGTCGCACCATCATCAACTCGAGTTGATGATGGTGCGACTGTTGTTTTTG 1469 chr15 ENST00000622074.1 GREM2 CCGGGCTGTGAAGGAAGGAAATTTACTCGAGTAAATTTCCTTCCTTCACAGCTTTTTG 1470 chr1 ENST00000318160.4 GREM2 CCGGCAAGGTGCATTTCTGTCATTTCTCGAGAAATGACAGAAATGCACCTTGTTTTTG 1471 chr1 ENST00000318160.4 GREM2 CCGGCGGAAGTAGACGTAACTTATTCTCGAGAATAAGTTACGTCTACTTCCGTTTTTG 1472 chr1 ENST00000318160.4 GRN CCGGGCCCTGATAGTCAGTTCGAATCTCGAGATTCGAACTGACTATCAGGGCTTTTTG 1473 chr17 ENST00000053867.7 GRN CCGGGCCCTGATAGTCAGTTCGAATCTCGAGATTCGAACTGACTATCAGGGCTTTTTG 1474 chr17 ENST00000053867.7 GRN CCGGCTTCCAAAGATCAGGTAACAACTCGAGTTGTTACCTGATCTTTGGAAGTTTTTG 1475 chr17 ENST00000053867.7 HAX1 CCGGACAGACACTTCGGGACTCAATCTCGAGATTGAGTCCCGAAGTGTCTGTTTTTTG 1476 chr1 ENST00000328703.11 HAX1 CCGGCCAGCCCAAATCCTATTTCAACTCGAGTTGAAATAGGATTTGGGCTGGTTTTTG 1477 chr1 ENST00000328703.11 HAX1 CCGGCCAGAGGCCATTTCATAGGTTCTCGAGAACCTATGAAATGGCCTCTGGTTTTTG 1478 chr1 ENST00000328703.11 HFE2 CCGGGACATGATCATTAGCCATAAGCTCGAGCTTATGGCTAATGATCATGTCTTTTTG 1479 chr1 ENST00000336751.10 HFE2 CCGGGCCTACATTGGCACAACTATACTCGAGTATAGTTGTGCCAATGTAGGCTTTTTG 1480 chr1 ENST00000336751.10 HFE2 CCGGGAAGCTCACCATCATATTTAACTCGAGTTAAATATGATGGTGAGCTTCTTTTTG 1481 chr1 ENST00000336751.10 HMGB1 CCGGGATGCAGCTTATACGAAATAACTCGAGTTATTTCGTATAAGCTGCATCTTTTTG 1482 chr13 ENST00000339872.8 HMGB1 CCGGGTTGGTGCACAGCACAAATTACTCGAGTAATTTGTGCTGTGCACCAACTTTTTG 1483 chr13 ENST00000339872.8 HMGB1 CCGGAGAAGATGATGATGATGAATACTCGAGTATTCATCATCATCATCTTCTTTTTTG 1484 chr13 ENST00000339872.8 HYAL2 CCGGCCTGCCAGTACCTCAAAGATTCTCGAGAATCTTTGAGGTACTGGCAGGTTTTTG 1485 chr3 ENST00000357750.8 HYAL2 CCGGCCTGCCAGTACCTCAAAGATTCTCGAGAATCTTTGAGGTACTGGCAGGTTTTTG 1486 chr3 ENST00000357750.8 HYAL2 CCGGCTGGACCTGAATGCCTTTGATCTCGAGATCAAAGGCATTCAGGTCCAGTTTTTG 1487 chr3 ENST00000357750.8 ICAM3 CCGGGTCCAGCTCACGAGGCAAATACTCGAGTATTTGCCTCGTGAGCTGGACTTTTTG 1488 chr19 ENST00000160262.9 ICAM3 CCGGCCAGCTCAACTTCAGCTAAATCTCGAGATTTAGCTGAAGTTGAGCTGGTTTTTG 1489 chr19 ENST00000160262.9 ICAM3 CCGGGCACTTGAAATGGAAAGATAACTCGAGTTATCTTTCCATTTCAAGTGCTTTTTG 1490 chr19 ENST00000160262.9 ICAM3 CCGGGAGCGGCAGTTACCATGTTAGCTCGAGCTAACATGGTAACTGCCGCTCTTTTTG 1491 chr19 ENST00000160262.9 ICOS CCGGGCACGACCCTAACGGTGAATACTCGAGTATTCACCGTTAGGGTCGTGCTTTTTG 1492 ch2 ENST00000316386.10 ICOS CCGGGTCCGCATTTCACTATCATACCTCGAGGTATGATAGTGAAATGCGGACTTTTTG 1493 ch2 ENST00000316386.10 ICOS CCGGCCATTCTCATGCCAACTATTACTCGAGTAATAGTTGGCATGAGAATGGTTTTTG 1494 ch2 ENST00000316386.10 ICOS CCGGCACAGATGTGACCCTATAATACTCGAGTATTATAGGGTCACATCTGTGTTTTTG 1495 ch2 ENST00000316386.10 IFNA10 CCGGTGTAAAGAAGTGTCGTGTATACTCGAGTATACACGACACTTCTTTACATTTTTG 1496 chr9 ENST00000357374.2 IFNA10 CCGGATAACCACGACGCGTTGAATCCTCGAGGATTCAACGCGTCGTGGTTATTTTTTG 1497 chr9 ENST00000357374.2 IFNA10 CCGGCCTGGGACAAATGGGAAGAATCTCGAGATTCTTCCCATTTGTCCCAGGTTTTTG 1498 chr9 ENST00000357374.2 IFNA14 CCGGCTGGGCTGTAATCTGTCTCAACTCGAGTTGAGACAGATTACAGCCCAGTTTTTG 1499 chr9 ENST00000380222.3 IFNA14 CCGGCCTGAATAACAGGAGGACTTTCTCGAGAAAGTCCTCCTGTTATTCAGGTTTTTG 1500 chr9 ENST00000380222.3 IFNA14 CCGGGCAGCAGACCTTCAATCTCTTCTCGAGAAGAGATTGAAGGTCTGCTGCTTTTTG 1501 chr9 ENST00000380222.3 IFNA16 CCGGTGTAAAGAAGCATCGTGTTTACTCGAGTAAACACGATGCTTCTTTACATTTTTG 1502 chr9 ENST00000380216.1 IFNA16 CCGGATGATCCTCATTGATTAATACCTCGAGGTATTAATCAATGAGGATCATTTTTTG 1503 chr9 ENST00000380216.1 IFNA16 CCGGCCTGAAGGACAGATATGATTTCTCGAGAAATCATATCTGTCCTTCAGGTTTTTG 1504 chr9 ENST00000380216.1 IFNA2 CCGGGCACAGTGGTTAATGTAATAACTCGAGTTATTACATTAACCACTGTGCTTTTTG 1505 chr9 ENST00000380206.3 IFNA2 CCGGTATGACCATGACACGATTTAACTCGAGTTAAATCGTGTCATGGTCATATTTTTG 1506 chr9 ENST00000380206.3 IFNA2 CCGGCCATGCTGACTGATCCATTATCTCGAGATAATGGATCAGTCAGCATGGTTTTTG 1507 chr9 ENST00000380206.3 IFNA5 CCGGACTTGGGATGAGACACTTCTACTCGAGTAGAAGTGTCTCATCCCAAGTTTTTTG 1508 chr9 ENST00000610521.1 IFNA5 CCGGAGTGGAAGACACTCCTCTGATCTCGAGATCAGAGGAGTGTCTTCCACTTTTTTG 1509 chr9 ENST00000610521.1 IFNA5 CCGGTCAACTGCAAGTCAATCTGTTCTCGAGAACAGATTGACTTGCAGTTGATTTTTG 1510 chr9 ENST00000610521.1 IFNA6 CCGGGACAGACATGACTTCAGATTTCTCGAGAAATCTGAAGTCATGTCTGTCTTTTTG 1511 chr9 ENST00000380210.1 IFNA6 CCGGCTGTCCTCCATGAGGTGATTCCTCGAGGAATCACCTCATGGAGGACAGTTTTTG 1512 chr9 ENST00000380210.1 IFNA6 CCGGAGGCTTCTAGACAAACTCTATCTCGAGATAGAGTTTGTCTAGAAGCCTTTTTTG 1513 chr9 ENST00000380210.1 IFNA8 CCGGTAACTATCTATAGGGCTTAAACTCGAGTTTAAGCCCTATAGATAGTTATTTTTG 1514 chr9 ENST00000380205.1 IFNA8 CCGGCCAGGAGGAGTTTGATGATAACTCGAGTTATCATCAAACTCCTCCTGGTTTTTG 1515 chr9 ENST00000380205.1 IFNA8 CCGGGACCTGGTACAACACGGAAATCTCGAGATTTCCGTGTTGTACCAGGTCTTTTTG 1516 chr9 ENST00000380205.1 IFNAR1 CCGGGCCAAGATTCAGGAAATTATTCTCGAGAATAATTTCCTGAATCTTGGCTTTTTG 1517 chr21 ENST00000270139.7 IFNAR1 CCGGGCTCTCCCGTTTGTCATTTATCTCGAGATAAATGACAAACGGGAGAGCTTTTTG 1518 chr21 ENST00000270139.7 IFNAR1 CCGGATGAACTGTGTCAAGTATAAGCTCGAGCTTATACTTGACACAGTTCATTTTTTG 1519 chr21 ENST00000270139.7 IFNAR2 CCGGGAGTGGAAATTTCACCTATATCTCGAGATATAGGTGAAATTTCCACTCTTTTTG 1520 chr21 ENST00000342136.8 IFNAR2 CCGGTGTATATCAGCCTCGTGTTTGCTCGAGCAAACACGAGGCTGATATACATTTTTG 1521 chr21 ENST00000342136.8 IFNAR2 CCGGGCAAATACCACAAGATCATTTCTCGAGAAATGATCTTGTGGTATTTGCTTTTTG 1522 chr21 ENST00000342136.8 IFNB1 CCGGATTGAATGGGAGGCTTGAATACTCGAGTATTCAAGCCTCCCATTCAATTTTTTG 1523 chr9 ENST00000380232.3 IFNB1 CCGGCCTACAAAGAAGCAGCAATTTCTCGAGAAATTGCTGCTTCTTTGTAGGTTTTTG 1524 chr9 ENST00000380232.3 IFNB1 CCGGCTAATGTCTATCATCAGATAACTCGAGTTATCTGATGATAGACATTAGTTTTTG 1525 chr9 ENST00000380232.3 IFNE CCGGGGTAGTGATAACCTTAGATTACTCGAGTAATCTAAGGTTATCACTACCTTTTTG 1526 chr9 ENST00000448696.4 IFNE CCGGAGCCTCTTCAGGGCAAATATTCTCGAGAATATTTGCCCTGAAGAGGCTTTTTTG 1527 chr9 ENST00000448696.4 IFNE CCGGCATAGAGTGGTAATACAATTTCTCGAGAAATTGTATTACCACTCTATGTTTTTG 1528 chr9 ENST00000448696.4 IFNG CCGGGGTTGTCCTGCCTGCAATATTCTCGAGAATATTGCAGGCAGGACAACCTTTTTG 1529 chr12 ENST00000229135.3 IFNG CCGGCATTCAGATGTAGCGGATAATCTCGAGATTATCCGCTACATCTGAATGTTTTTG 1530 chr12 ENST00000229135.3 IFNG CCGGTGTTACTGCCAGGACCCATATCTCGAGATATGGGTCCTGGCAGTAACATTTTTG 1531 chr12 ENST00000229135.3 IFNGR1 CCGGACGAGCAGGAAGTCGATTATGCTCGAGCATAATCGACTTCCTGCTCGTTTTTTG 1532 chr6 ENST00000367739.8 IFNGR1 CCGGCATGAACCCTATCGTATATTGCTCGAGCAATATACGATAGGGTTCATGTTTTTG 1533 chr6 ENST00000367739.8 IFNGR1 CCGGCGGAAGTGAGATCCAGTATAACTCGAGTTATACTGGATCTCACTTCCGTTTTTG 1534 chr6 ENST00000367739.8 IFNK CCGGGAGATTGTGGCTACGCAAATGCTCGAGCATTTGCGTAGCCACAATCTCTTTTTG 1535 chr9 ENST00000276943.2 IFNK CCGGCTGTTCAGATTCAAGATTATTCTCGAGAATAATCTTGAATCTGAACAGTTTTTG 1536 chr9 ENST00000276943.2 IFNK CCGGTCAGCCAACACACCTTCAAATCTCGAGATTTGAAGGTGTGTTGGCTGATTTTTG 1537 chr9 ENST00000276943.2 IFNL1 CCGGCTCACGCGAGACCTCAAATATCTCGAGATATTTGAGGTCTCGCGTGAGTTTTTG 1538 chr19 ENST00000333625.2 IFNL1 CCGGGCCACATTGGCAGGTTCAAATCTCGAGATTTGAACCTGCCAATGTGGCTTTTTG 1539 chr19 ENST00000333625.2 IFNL1 CCGGGAGTTGCAGCTCTCCTGTCTTCTCGAGAAGACAGGAGAGCTGCAACTCTTTTTG 1540 chr19 ENST00000333625.2 IFNL3 CCGGAGGGCCAAAGATGCCTTAGAACTCGAGTTCTAAGGCATCTTTGGCCCTTTTTTG 1541 chr19 ENST00000413851.2 IFNL3 CCGGGCCTTTAAGAGGGCCAAAGATCTCGAGATCTTTGGCCCTCTTAAAGGCTTTTTG 1542 chr19 ENST00000413851.2 IFNL3 CCGGTGCCACATAGCCCAGTTCAAGCTCGAGCTTGAACTGGGCTATGTGGCATTTTTG 1543 chr19 ENST00000413851.2 IFNW1 CCGGAGACTCTTATTTCGGCTTTAACTCGAGTTAAAGCCGAAATAAGAGTCTTTTTTG 1544 chr9 ENST00000380229.3

IFNW1 CCGGTCAGTCCCTAAGATGTTATTTCTCGAGAAATAACATCTTAGGGACTGATTTTTG 1545 chr9 ENST00000380229.3 IFNW1 CCGGCGGTATATTAAGCCAGTATATCTCGAGATATACTGGCTTAATATACCGTTTTTG 1546 chr9 ENST00000380229.3 IL10 CCGGAGCTTCTCTGTGAACGATTTACTCGAGTAAATCGTTCACAGAGAAGCTTTTTTG 1547 chr1 ENST00000423557.1 IL10 CCGGGCAGGTGAAGAATGCCTTTAACTCGAGTTAAAGGCATTCTTCACCTGCTTTTTG 1548 chr1 ENST00000423557.1 IL10 CCGGGCTGGACAACTTGTTGTTAAACTCGAGTTTAACAACAAGTTGTCCAGCTTTTTG 1549 chr1 ENST00000423557.1 IL10RA CCGGTCTGTCGCTTCCCGAAGTAACCTCGAGGTTACTTCGGGAAGCGACAGATTTTTG 1550 chr11 ENST00000227752.7 IL10RA CCGGGAAACAGGATCCTCTAGAAATCTCGAGATTTCTAGAGGATCCTGTTTCTTTTTG 1551 chr11 ENST00000227752.7 IL10RA CCGGGAACTCTTTCCTGTATCATAACTCGAGTTATGATACAGGAAAGAGTTCTTTTTG 1552 chr11 ENST00000227752.7 IL11 CCGGATATCCACTTGAGGGCGATTTCTCGAGAAATCGCCCTCAAGTGGATATTTTTTG 1553 chr19 ENST00000264563.6 IL11 CCGGCCTTCCAAAGCCAGATCTTATCTCGAGATAAGATCTGGCTTTGGAAGGTTTTTG 1554 chr19 ENST00000264563.6 IL11 CCGGTGCACAGCTGAGGGACAAATTCTCGAGAATTTGTCCCTCAGCTGTGCATTTTTG 1555 chr19 ENST00000264563.6 IL11RA CCGGCGGCAGATTCCACCTATAATTCTCGAGAATTATAGGTGGAATCTGCCGTTTTTG 1556 chr9 ENST00000318041.13 IL11RA CCGGTCGGCAGATTCCACCTATAATCTCGAGATTATAGGTGGAATCTGCCGATTTTTG 1557 chr9 ENST00000318041.13 IL11RA CCGGTGGAGCCAGTACCGGATTAATCTCGAGATTAATCCGGTACTGGCTCCATTTTTG 1558 chr9 ENST00000318041.13 IL12A CCGGTGATACCTCTGATCAAGTATTCTCGAGAATACTTGATCAGAGGTATCATTTTTG 1559 chr3 ENST00000305579.6 IL12A CCGGCCTGTGCCTTAGTAGTATTTACTCGAGTAAATACTACTAAGGCACAGGTTTTTG 1560 chr3 ENST00000305579.6 IL12A CCGGCCTGTTTACCATTGGAATTAACTCGAGTTAATTCCAATGGTAAACAGGTTTTTG 1561 chr3 ENST00000305579.6 IL12B CCGGGAATTTGGTCCACTGATATTTCTCGAGAAATATCAGTGGACCAAATTCTTTTTG 1562 chr5 ENST00000231228.2 IL12B CCGGCCATGGGCCTTCATGCTATTTCTCGAGAAATAGCATGAAGGCCCATGGTTTTTG 1563 chr5 ENST00000231228.2 IL12B CCGGTTAGATGCTAAATGCTCATTGCTCGAGCAATGAGCATTTAGCATCTAATTTTTG 1564 chr5 ENST00000231228.2 IL12RB1 CCGGCAGCTCTACAACTCAGTTAAACTCGAGTTTAACTGAGTTGTAGAGCTGTTTTTG 1565 chr19 ENST00000593993.6 IL12RB1 CCGGGTCATCTCCTCGAACCAATTTCTCGAGAAATTGGTTCGAGGAGATGACTTTTTG 1566 chr19 ENST00000593993.6 IL12RB1 CCGGCCAACGGGACCACCATGTATTCTCGAGAATACATGGTGGTCCCGTTGGTTTTTG 1567 chr19 ENST00000593993.6 IL13 CCGGACTTCGAAAGCATCATTATTTCTCGAGAAATAATGATGCTTTCGAAGTTTTTTG 1568 chr5 ENST00000304506.7 IL13 CCGGATTGAAGTTGCAGATTCATTTCTCGAGAAATGAATCTGCAACTTCAATTTTTTG 1569 chr5 ENST00000304506.7 IL13 CCGGCCTGCTCTTACATTTAAAGAACTCGAGTTCTTTAAATGTAAGAGCAGGTTTTTG 1570 chr5 ENST00000304506.7 IL15 CCGGGAAGATCTTATTCAATCTATGCTCGAGCATAGATTGAATAAGATCTTCTTTTTG 1571 chr4 ENST00000296545.11 IL15 CCGGTAAGGGTGATAGTCAAATTATCTCGAGATAATTTGACTATCACCCTTATTTTTG 1572 chr4 ENST00000296545.11 IL15 CCGGCACTCTGCTGCTTAGACATAACTCGAGTTATGTCTAAGCAGCAGAGTGTTTTTG 1573 chr4 ENST00000296545.11 IL16 CCGGTGGGACCACGTGAGATCATTCCTCGAGGAATGATCTCACGTGGTCCCATTTTTG 1574 chr15 ENST00000302987.8 IL16 CCGGGTTCTGGATGAAGCAACATTACTCGAGTAATGTTGCTTCATCCAGAACTTTTTG 1575 chr15 ENST00000302987.8 IL16 CCGGCCCAAACAGTGACATTTATTTCTCGAGAAATAAATGTCACTGTTTGGGTTTTTG 1576 chr15 ENST00000302987.8 IL17A CCGGATCAGTTCTGCCTAGGTAAATCTCGAGATTTACCTAGGCAGAACTGATTTTTTG 1577 chr6 ENST00000340057.1 IL17A CCGGGAGCTATTTAAGGATCTATTTCTCGAGAAATAGATCCTTAAATAGCTCTTTTTG 1578 chr6 ENST00000340057.1 IL17A CCGGGGTCAACCTGAACATCCATAACTCGAGTTATGGATGTTCAGGTTGACCTTTTTG 1579 chr6 ENST00000340057.1 IL17B CCGGTATGCCCGCATGGAGGAGTATCTCGAGATACTCCTCCATGCGGGCATATTTTTG 1580 chr5 ENST00000261796.3 IL17B CCGGGTGTCACGGATGAAACCGTATCTCGAGATACGGTTTCATCCGTGACACTTTTTG 1581 chr5 ENST00000261796.3 IL17B CCGGGCAGCTGTGGATGTCCAACAACTCGAGTTGTTGGACATCCACAGCTGCTTTTTG 1582 chr5 ENST00000261796.3 IL17C CCGGGCACCTCTTCCAGCCCTTAAACTCGAGTTTAAGGGCTGGAAGAGGTGCTTTTTG 1583 chr16 ENST00000244241.4 IL17C CCGGCTTTGCCTTCCACACCGAGTTCTCGAGAACTCGGTGTGGAAGGCAAAGTTTTTG 1584 chr16 ENST00000244241.4 IL17C CCGGATCTCCAGCCTCAGTAGTTGGCTCGAGCCAACTACTGAGGCTGGAGATTTTTTG 1585 chr16 ENST00000244241.4 IL17D CCGGAGAGCTACTCTGTTACATTTCCTCGAGGAAATGTAACAGAGTAGCTCTTTTTTG 1586 chr13 ENST00000304920.3 IL17D CCGGCAAAGAGATAGGGACGCATATCTCGAGATATGCGTCCCTATCTCTTTGTTTTTG 1587 chr13 ENST00000304920.3 IL17D CCGGAGACAGCATCAACTCCAGCATCTCGAGATGCTGGAGTTGATGCTGTCTTTTTTG 1588 chr13 ENST00000304920.3 IL17F CCGGTCATCCACCATGTGCAGTAAGCTCGAGCTTACTGCACATGGTGGATGATTTTTG 1589 chr6 ENST00000336123.4 IL17F CCGGGTACTTGCTGCTGTCGATATTCTCGAGAATATCGACAGCAGCAAGTACTTTTTG 1590 chr6 ENST00000336123.4 IL17F CCGGCGTTTCCATGTCACGTAACATCTCGAGATGTTACGTGACATGGAAACGTTTTTG 1591 chr6 ENST00000336123.4 IL18 CCGGCCCGGACCATATTTATTATAACTCGAGTTATAATAAATATGGTCCGGGTTTTTG 1592 chr11 ENST00000280357.11 IL18 CCGGTGATTCTGACTGTAGAGATAACTCGAGTTATCTCTACAGTCAGAATCATTTTTG 1593 chr11 ENST00000280357.11 IL18 CCGGTGGCAAGCTTGAATCTAAATTCTCGAGAATTTAGATTCAAGCTTGCCATTTTTG 1594 chr11 ENST00000280357.11 IL18BP CCGGGGTCCCTTCTCTCACCAAATTCTCGAGAATTTGGTGAGAGAAGGGACCTTTTTG 1595 chr11 ENST00000260049.9 IL18BP CCGGTCCCATGTCTCTGCTCATTTACTCGAGTAAATGAGCAGAGACATGGGATTTTTG 1596 chr11 ENST00000260049.9 IL18BP CCGGCTGGGCAATGGTTCCTTCATTCTCGAGAATGAAGGAACCATTGCCCAGTTTTTG 1597 chr11 ENST00000260049.9 IL19 CCGGGTCCACGCTGCTGCCATTAAACTCGAGTTTAATGGCAGCAGCGTGGACTTTTTG 1598 chrl ENST00000270218.10 IL19 CCGGTCCACAGACATGCACCATATACTCGAGTATATGGTGCATGTCTGTGGATTTTTG 1599 chrl ENST00000270218.10 IL19 CCGGTGATGACAAGGAACCTGTATACTCGAGTATACAGGTTCCTTGTCATCATTTTTG 1600 chrl ENST00000270218.10 IL1A CCGGGTGGAACCAACACTAACATATCTCGAGATATGTTAGTGTTGGTTCCACTTTTTG 1601 chr2 ENST00000263339.3 IL1A CCGGGCCCTCAATCAAAGTATAATTCTCGAGAATTATACTTTGATTGAGGGCTTTTTG 1602 chr2 ENST00000263339.3 IL1A CCGGTATTACAGATGGGCAAATTAACTCGAGTTAATTTGCCCATCTGTAATATTTTTG 1603 chr2 ENST00000263339.3 IL1B CCGGATCAATAACAAGCTGGAATTTCTCGAGAAATTCCAGCTTGTTATTGATTTTTTG 1604 chr2 ENST00000263341.6 IL1B CCGGAGCAACCGCTTCCCTATTTATCTCGAGATAAATAGGGAAGCGGTTGCTTTTTTG 1605 chr2 ENST00000263341.6 IL1B CCGGCTGACTTCACCATGCAATTTGCTCGAGCAAATTGCATGGTGAAGTCAGTTTTTG 1606 chr2 ENST00000263341.6 IL1F10 CCGGTCCTTGTGGGCTCAGTTTAATCTCGAGATTAAACTGAGCCCACAAGGATTTTTG 1607 chr2 ENST00000341010.6 IL1F10 CCGGGGTCTATGGTAGGCAGAATAACTCGAGTTATTCTGCCTACCATAGACCTTTTTG 1608 chr2 ENST00000341010.6 IL1F10 CCGGTGCAGACCAGAAGGCTCTATACTCGAGTATAGAGCCTTCTGGTCTGCATTTTTG 1609 chr2 ENST00000341010.6 IL1R1 CCGGGCCAAGAATACACATGGTATACTCGAGTATACCATGTGTATTCTTGGCTTTTTG 1610 chr2 ENST00000410023.5 IL1R1 CCGGATAATGCACAAGCCATATTTACTCGAGTAAATATGGCTTGTGCATTATTTTTTG 1611 chr2 ENST00000410023.5 IL1R1 CCGGTGGTATAGATGCAGCATATATCTCGAGATATATGCTGCATCTATACCATTTTTG 1612 chr2 ENST00000410023.5 IL1R2 CCGGCAATCCCGTGTAAGGTGTTTCCTCGAGGAAACACCTTACACGGGATTGTTTTTG 1613 chr2 ENST00000332549.7 IL1R2 CCGGGACCATTCCTGTGATCATTTCCTCGAGGAAATGATCACAGGAATGGTCTTTTTG 1614 chr2 ENST00000332549.7 IL1R2 CCGGCGTTCATCTCATACCCGCAAACTCGAGTTTGCGGGTATGAGATGAACGTTTTTG 1615 chr2 ENST00000332549.7 IL1RAPL1 CCGGCAAAGCAAGCGGCTGATTATTCTCGAGAATAATCAGCCGCTTGCTTTGTTTTTG 1616 chrX ENST00000378993.5 IL1RAPL1 CCGGGCCAGCGTTCTCCTTCATAAACTCGAGTTTATGAAGGAGAACGCTGGCTTTTTG 1617 chrX ENST00000378993.5 IL1RAPL1 CCGGTCAAGCTCCTGACGGTCATTACTCGAGTAATGACCGTCAGGAGCTTGATTTTTG 1618 chrX ENST00000378993.5 IL1RL1 CCGGTTACACCGTGGATTGGTATTACTCGAGTAATACCAATCCACGGTGTAATTTTTG 1619 chr2 ENST00000233954.5 IL1RL1 CCGGAGTTGCTGATTCTGGTATTTACTCGAGTAAATACCAGAATCAGCAACTTTTTTG 1620 chr2 ENST00000233954.5 IL1RL1 CCGGCGTGAAGGAAGAGGATTTATTCTCGAGAATAAATCCTCTTCCTTCACGTTTTTG 1621 chr2 ENST00000233954.5 IL1RN CCGGGCAAGGACCAAATGTCAATTTCTCGAGAAATTGACATTTGGTCCTTGCTTTTTG 1622 chr2 ENST00000409930.3 IL1RN CCGGCGTCATGGTCACCAAATTCTACTCGAGTAGAATTTGGTGACCATGACGTTTTTG 1623 chr2 ENST00000409930.3 IL1RN CCGGCTGCCTCCAGAATGGTCTTTCCTCGAGGAAAGACCATTCTGGAGGCAGTTTTTG 1624 chr2 ENST00000409930.3 IL2 CCGGGCTACCTATTGTAACTATTATCTCGAGATAATAGTTACAATAGGTAGCTTTTTG 1625 chr4 ENST00000226730.4 IL2 CCGGCAGCTACAACTGGAGCATTTACTCGAGTAAATGCTCCAGTTGTAGCTGTTTTTG 1626 chr4 ENST00000226730.4 IL2 CCGGTGCTGGATTTACAGATGATTTCTCGAGAAATCATCTGTAAATCCAGCATTTTTG 1627 chr4 ENST00000226730.4 IL20 CCGGCTGATGCTCTGTGAGATATTTCTCGAGAAATATCTCACAGAGCATCAGTTTTTG 1628 chr1

ENST00000367096.7 IL20 CCGGTGGTCACAGTGTATCTTATTTCTCGAGAAATAAGATACACTGTGACCATTTTTG 1629 chr1 ENST00000367096.7 IL20 CCGGGGACTGAAGACACTCAATTTGCTCGAGCAAATTGAGTGTCTTCAGTCCTTTTTG 1630 chr1 ENST00000367096.7 IL20RA CCGGCCAGTATTATGCCAAAGTTAACTCGAGTTAACTTTGGCATAATACTGGTTTTTG 1631 chr6 ENST00000316649.9 IL20RA CCGGGAGGGTCTTCAAGGAGTTAAACTCGAGTTTAACTCCTTGAAGACCCTCTTTTTG 1632 chr6 ENST00000316649.9 IL20RA CCGGGCTTCGCATTTGATGGAAATTCTCGAGAATTTCCATCAAATGCGAAGCTTTTTG 1633 chr6 ENST00000316649.9 IL20RB CCGGCAGTGTACTATTCTGTCGAATCTCGAGATTCGACAGAATAGTACACTGTTTTTG 1634 chr3 ENST00000329582.8 IL20RB CCGGCCAGAATAATCCTTGAGAGAACTCGAGTTCTCTCAAGGATTATTCTGGTTTTTG 1635 chr3 ENST00000329582.8 IL20RB CCGGCTCTGTACTCTCAACCAACATCTCGAGATGTTGGTTGAGAGTACAGAGTTTTTG 1636 chr3 ENST00000329582.8 IL21 CCGGAGGAAACCACCTTCCACAAATCTCGAGATTTGTGGAAGGTGGTTTCCTTTTTTG 1637 chr4 ENST00000264497.7 IL21 CCGGATGACTTGGTCCCTGAATTTCCTCGAGGAAATTCAGGGACCAAGTCATTTTTTG 1638 chr4 ENST00000264497.7 IL21 CCGGCTTTCAGAAGGCCCAACTAAACTCGAGTTTAGTTGGGCCTTCTGAAAGTTTTTG 1639 chr4 ENST00000264497.7 IL22 CCGGAGGCTAAGCACATGTCATATTCTCGAGAATATGACATGTGCTTAGCCTTTTTTG 1640 chr12 ENST00000328087.5 IL22 CCGGGTTTCCATAATCAGTACTTTACTCGAGTAAAGTACTGATTATGGAAACTTTTTG 1641 chr12 ENST00000328087.5 IL22 CCGGAGACTTTCTAAGCATAGATATCTCGAGATATCTATGCTTAGAAAGTCTTTTTTG 1642 chr12 ENST00000328087.5 IL22RA1 CCGGGGACACTTTCTAGTCCTAAACCTCGAGGTTTAGGACTAGAAAGTGTCCTTTTTG 1643 chr1 ENST00000270800.1 IL22RA1 CCGGAGGGACACCACAGTACCTAAACTCGAGTTTAGGTACTGTGGTGTCCCTTTTTTG 1644 chr1 ENST00000270800.1 IL22RA1 CCGGCTGTCCGAGATCACCTACTTACTCGAGTAAGTAGGTGATCTCGGACAGTTTTTG 1645 chr1 ENST00000270800.1 IL22RA2 CCGGAGACATACAGGAACCTTATTACTCGAGTAATAAGGTTCCTGTATGTCTTTTTTG 1646 chr6 ENST00000349184.8 IL22RA2 CCGGCTCGTGTTTGAAGGATCTTATCTCGAGATAAGATCCTTCAAACACGAGTTTTTG 1647 chr6 ENST00000349184.8 IL22RA2 CCGGTGCTCCAAATTTACCATATAGCTCGAGCTATATGGTAAATTTGGAGCATTTTTG 1648 chr6 ENST00000349184.8 IL23A CCGGAGCTGCTAGGATCGGATATTTCTCGAGAAATATCCGATCCTAGCAGCTTTTTTG 1649 chr12 ENST00000228534.5 IL23A CCGGCTGTGAGCCAACAGGTTAATTCTCGAGAATTAACCTGTTGGCTCACAGTTTTTG 1650 chr12 ENST00000228534.5 IL23A CCGGGGATCCACCAGGGTCTGATTTCTCGAGAAATCAGACCCTGGTGGATCCTTTTTG 1651 chr12 ENST00000228534.5 IL23R CCGGCTTTCTTTGATTGGGATATTTCTCGAGAAATATCCCAATCAAAGAAAGTTTTTG 1652 chr1 ENST00000347310.9 IL23R CCGGTATCTCACCTCAAGCTATATTCTCGAGAATATAGCTTGAGGTGAGATATTTTTG 1653 chr1 ENST00000347310.9 IL23R CCGGCGACAATACTACAGTTGTATACTCGAGTATACAACTGTAGTATTGTCGTTTTTG 1654 chr1 ENST00000347310.9 IL24 CCGGCACAGGCGGTTTCTGCTATTCCTCGAGGAATAGCAGAAACCGCCTGTGTTTTTG 1655 chr1 ENST00000294984.6 IL24 CCGGGTCAGGACTCTGAAGTCATTCCTCGAGGAATGACTTCAGAGTCCTGACTTTTTG 1656 chr1 ENST00000294984.6 IL24 CCGGTCGGATGCTGAGAGCTGTTACCTCGAGGTAACAGCTCTCAGCATCCGATTTTTG 1657 chr1 ENST00000294984.6 IL25 CCGGACAGGCACTTTCTAGATATTTCTCGAGAAATATCTAGAAAGTGCCTGTTTTTTG 1658 chr14 ENST00000329715.2 IL25 CCGGCCACAACCAGACTGTCTTCTACTCGAGTAGAAGACAGTCTGGTTGTGGTTTTTG 1659 chr14 ENST00000329715.2 IL25 CCGGTCCTGTAGGGCCAGTGAAGATCTCGAGATCTTCACTGGCCCTACAGGATTTTTG 1660 chr14 ENST00000329715.2 IL26 CCGGAGCTGTTGACGCTCTCTATATCTCGAGATATAGAGAGCGTCAACAGCTTTTTTG 1661 chr12 ENST00000229134.4 IL26 CCGGAGTACATTGTGTCAACTTAATCTCGAGATTAAGTTGACACAATGTACTTTTTTG 1662 chr12 ENST00000229134.4 IL26 CCGGCGATTCCAGAAGACCGCATAACTCGAGTTATGCGGTCTTCTGGAATCGTTTTTG 1663 chr12 ENST00000229134.4 IL27 CCGGACTCCTTGGAGCTCGTCTTATCTCGAGATAAGACGAGCTCCAAGGAGTTTTTTG 1664 chr16 ENST00000356897.1 IL27 CCGGACTTTAGGACTGGAGTCTTGGCTCGAGCCAAGACTCCAGTCCTAAAGTTTTTTG 1665 chr16 ENST00000356897.1 IL27 CCGGCATCATCAGCCTTGGACAAGGCTCGAGCCTTGTCCAAGGCTGATGATGTTTTTG 1666 chr16 ENST00000356897.1 IL2RA CCGGCCTCGTCACAACAACAGATTTCTCGAGAAATCTGTTGTTGTGACGAGGTTTTTG 1667 chr10 ENST00000379959.7 IL2RA CCGGACCCTATACAACTGGACATTGCTCGAGCAATGTCCAGTTGTATAGGGTTTTTTG 1668 chr10 ENST00000379959.7 IL2RA CCGGACTCGGAACACAACGAAACAACTCGAGTTGTTTCGTTGTGTTCCGAGTTTTTTG 1669 chr10 ENST00000379959.7 IL2RB CCGGAGTCCCAGACCTGGTGGATTTCTCGAGAAATCCACCAGGTCTGGGACTTTTTTG 1670 chr22 ENST00000216223.9 IL2RB CCGGGACCCACAGATGCAACATAAGCTCGAGCTTATGTTGCATCTGTGGGTCTTTTTG 1671 chr22 ENST00000216223.9 IL2RB CCGGCCAGACACCCAGTATGAGTTTCTCGAGAAACTCATACTGGGTGTCTGGTTTTTG 1672 chr22 ENST00000216223.9 IL2RG CCGGTCGTGTTCGGAGCCGCTTTAACTCGAGTTAAAGCGGCTCCGAACACGATTTTTG 1673 chrX ENST00000374202.6 IL2RG CCGGCCAACCTCACTCTGCATTATTCTCGAGAATAATGCAGAGTGAGGTTGGTTTTTG 1674 chrX ENST00000374202.6 IL2RG CCGGTTGGCTCCATGGGATTGATTACTCGAGTAATCAATCCCATGGAGCCAATTTTTG 1675 chrX ENST00000374202.6 IL3 CCGGTTATCCCATTGAGACTATTTACTCGAGTAAATAGTCTCAATGGGATAATTTTTG 1676 chr5 ENST00000296870.2 IL3 CCGGCGGCATCAGATGAATTGTTAACTCGAGTTAACAATTCATCTGATGCCGTTTTTG 1677 chr5 ENST00000296870.2 IL3 CCGGGCAATTGAGAGCATTCTTAAACTCGAGTTTAAGAATGCTCTCAATTGCTTTTTG 1678 chr5 ENST00000296870.2 IL31 CCGGGCATATCTCAAGACAATCAGACTCGAGTCTGATTGTCTTGAGATATGCTTTTTG 1679 chr12 ENST00000377035.1 IL31 CCGGCCAAGTGATGATGTACAGAAACTCGAGTTTCTGTACATCATCACTTGGTTTTTG 1680 chr12 ENST00000377035.1 IL31 CCGGCCTGACTATTTCTCAACAGTTCTCGAGAACTGTTGAGAAATAGTCAGGTTTTTG 1681 chr12 ENST00000377035.1 IL31RA CCGGCATCAAACGAATGATTCAAATCTCGAGATTTGAATCATTCGTTTGATGTTTTTG 1682 chr5 ENST00000447346.6 IL31RA CCGGCGCCTGTTTCATCTGATTTAACTCGAGTTAAATCAGATGAAACAGGCGTTTTTG 1683 chr5 ENST00000447346.6 IL31RA CCGGTTTCCTGTGTCTACTACTATACTCGAGTATAGTAGTAGACACAGGAAATTTTTG 1684 chr5 ENST00000447346.6 IL32 CCGGTGTCGCCCTGGCATCTTAATACTCGAGTATTAAGATGCCAGGGCGACATTTTTG 1685 chr16 ENST00000325568.9 IL32 CCGGAGAGCTCACTCCTCTACTTGACTCGAGTCAAGTAGAGGAGTGAGCTCTTTTTTG 1686 chr16 ENST00000325568.9 IL32 CCGGAGAGCTGGAGGACGACTTCAACTCGAGTTGAAGTCGTCCTCCAGCTCTTTTTTG 1687 chr16 ENST00000325568.9 IL33 CCGGGAGTGCTTTGCCTTTGGTATACTCGAGTATACCAAAGGCAAAGCACTCTTTTTG 1688 chr9 ENST00000381434.7 IL33 CCGGGCACTCCAACTGTGTTTCATTCTCGAGAATGAAACACAGTTGGAGTGCTTTTTG 1689 chr9 ENST00000381434.7 IL33 CCGGCCTGTTACTTTAGGAGAGAAACTCGAGTTTCTCTCCTAAAGTAACAGGTTTTTG 1690 chr9 ENST00000381434.7 IL34 CCGGGCCGACTTCAGTACATGAAACCTCGAGGTTTCATGTACTGAAGTCGGCTTTTTG 1691 chr16 ENST00000288098.6 IL34 CCGGCAGAGCCCTCATTGCAGTATGCTCGAGCATACTGCAATGAGGGCTCTGTTTTTG 1692 chr16 ENST00000288098.6 IL34 CCGGCCGTGTTGTCCCTCTTGAATGCTCGAGCATTCAAGAGGGACAACACGGTTTTTG 1693 chr16 ENST00000288098.6 IL36A CCGGCTCCAGTCACTATTGCCTTAACTCGAGTTAAGGCAATAGTGACTGGAGTTTTTG 1694 chr2 ENST00000259211.6 IL36A CCGGTTCAGGACCAGACGCTCATAGCTCGAGCTATGAGCGTCTGGTCCTGAATTTTTG 1695 chr2 ENST00000259211.6 IL36A CCGGCTCTGCCTGATGTGTGCTAAACTCGAGTTTAGCACACATCAGGCAGAGTTTTTG 1696 chr2 ENST00000259211.6 IL36B CCGGATCCTATGCTATTCGTGATTCCTCGAGGAATCACGAATAGCATAGGATTTTTTG 1697 chr2 ENST00000327407.2 IL36B CCGGCCTGAGTGGAAATTCTTTAATCTCGAGATTAAAGAATTTCCACTCAGGTTTTTG 1698 chr2 ENST00000327407.2 IL36B CCGGTTGGACTACATAACCTGTAAACTCGAGTTTACAGGTTATGTAGTCCAATTTTTG 1699 chr2 ENST00000327407.2 IL36G CCGGTGATATCATCCAGTCTTTATACTCGAGTATAAAGACTGGATGATATCATTTTTG 1700 chr2 ENST00000259205.4 IL36G CCGGCAGGAGAGCTGGGTGGTATAACTCGAGTTATACCACCCAGCTCTCCTGTTTTTG 1701 chr2 ENST00000259205.4 IL36G CCGGGGGAATCCAGAATCCAGAAATCTCGAGATTTCTGGATTCTGGATTCCCTTTTTG 1702 chr2 ENST00000259205.4 IL36RN CCGGCTCGGCATTGAAGGTGCTTTACTCGAGTAAAGCACCTTCAATGCCGAGTTTTTG 1703 chr2 ENST00000346807.7 IL36RN CCGGTGGTTCCCAGTTTGGATAAATCTCGAGATTTATCCAAACTGGGAACCATTTTTG 1704 chr2 ENST00000346807.7 IL36RN CCGGGGGAATCATTCCTGCTTAATGCTCGAGCATTAAGCAGGAATGATTCCCTTTTTG 1705 chr2 ENST00000346807.7 IL37 CCGGCTCTACTGTGACAAGGATAAACTCGAGTTTATCCTTGTCACAGTAGAGTTTTTG 1706 chr2 ENST00000263326.7 IL37 CCGGTGCACCTCCTGCAATTGTAATCTCGAGATTACAATTGCAGGAGGTGCATTTTTG 1707 chr2 ENST00000263326.7 IL37 CCGGGTTCACACAAAGATCTTCTTTCTCGAGAAAGAAGATCTTTGTGTGAACTTTTTG 1708 chr2 ENST00000263326.7 IL4 CCGGAGCTGATCCGATTCCTGAAACCTCGAGGTTTCAGGAATCGGATCAGCTTTTTTG 1709 chr5 ENST00000231449.6 IL4 CCGGCCACGGACACAAGTGCGATATCTCGAGATATCGCACTTGTGTCCGTGGTTTTTG 1710 chr5 ENST00000231449.6 IL4 CCGGTAGCATGTGCCGGCAACTTTGCTCGAGCAAAGTTGCCGGCACATGCTATTTTTG 1711 chr5 ENST00000231449.6

IL5 CCGGGCAAGAGTTTCTTGGTGTAATCTCGAGATTACACCAAGAAACTCTTGCTTTTTG 1712 chr5 ENST00000231454.5 IL5 CCGGGGGTACTGTGGAAAGACTATTCTCGAGAATAGTCTTTCCACAGTACCCTTTTTG 1713 chr5 ENST00000231454.5 IL5 CCGGGAAAGAGTCAGGCCTTAATTTCTCGAGAAATTAAGGCCTGACTCTTTCTTTTTG 1714 chr5 ENST00000231454.5 IL6 CCGGATGAGCGTTAGGACACTATTTCTCGAGAAATAGTGTCCTAACGCTCATTTTTTG 1715 chr7 ENST00000258743.9 IL6 CCGGGAGTACCTCCAGAACAGATTTCTCGAGAAATCTGTTCTGGAGGTACTCTTTTTG 1716 chr7 ENST00000258743.9 IL6 CCGGATGTGAAGCTGAGTTAATTTACTCGAGTAAATTAACTCAGCTTCACATTTTTTG 1717 chr7 ENST00000258743.9 IL6R CCGGGCAGGCACTTACTACTAATAACTCGAGTTATTAGTAGTAAGTGCCTGCTTTTTG 1718 chr1 ENST00000368485.7 IL6R CCGGTATCGGGCTGAACGGTCAAAGCTCGAGCTTTGACCGTTCAGCCCGATATTTTTG 1719 chr1 ENST00000368485.7 IL6R CCGGCTGGACCCTGTGGATGATAAACTCGAGTTTATCATCCACAGGGTCCAGTTTTTG 1720 chr1 ENST00000368485.7 IL6ST CCGGACCGTGCATCGCACCTATTTACTCGAGTAAATAGGTGCGATGCACGGTTTTTTG 1721 chr5 ENST00000336909.9 IL6ST CCGGACTTCAGCAGTACCTATAAAGCTCGAGCTTTATAGGTACTGCTGAAGTTTTTTG 1722 chr5 ENST00000336909.9 IL6ST CCGGCGGCCAGAAGATCTACAATTACTCGAGTAATTGTAGATCTTCTGGCCGTTTTTG 1723 chr5 ENST00000336909.9 IL7 CCGGGCTCGCAAGTTGAGGCAATTTCTCGAGAAATTGCCTCAACTTGCGAGCTTTTTG 1724 chr8 ENST00000263851.8 IL7 CCGGGCTCACTATGAATCTATTATACTCGAGTATAATAGATTCATAGTGAGCTTTTTG 1725 chr8 ENST00000263851.8 IL7 CCGGGTGTTTCCTAAAGAGACTATTCTCGAGAATAGTCTCTTTAGGAAACACTTTTTG 1726 chr8 ENST00000263851.8 IL9 CCGGACCACCATGCAAACAAGATACCTCGAGGTATCTTGTTTGCATGGTGGTTTTTTG 1727 chr5 ENST00000274520.1 IL9 CCGGGAACAACAAGTGTCCATATTTCTCGAGAAATATGGACACTTGTTGTTCTTTTTG 1728 chr5 ENST00000274520.1 IL9 CCGGCTGAAGAGTCTTCTGGAAATTCTCGAGAATTTCCAGAAGACTCTTCAGTTTTTG 1729 chr5 ENST00000274520.1 INHA CCGGCCTCGGATGGAGGTTACTCTTCTCGAGAAGAGTAACCTCCATCCGAGGTTTTTG 1730 chr2 ENST00000243786.2 INHA CCGGGCAGCACTGTGCTTGTATCTACTCGAGTAGATACAAGCACAGTGCTGCTTTTTG 1731 chr2 ENST00000243786.2 INHA CCGGTGGAGGTTACTCTTTCAAGTACTCGAGTACTTGAAAGAGTAACCTCCATTTTTG 1732 chr2 ENST00000243786.2 INHBA CCGGAGGCACTTTCCTACCCAATTACTCGAGTAATTGGGTAGGAAAGTGCCTTTTTTG 1733 chr7 ENST00000242208.4 INHBA CCGGGAGAATGGTGTACCCTTTATTCTCGAGAATAAAGGGTACACCATTCTCTTTTTG 1734 chr7 ENST00000242208.4 INHBA CCGGAGACGCTGCACTTCGAGATTTCTCGAGAAATCTCGAAGTGCAGCGTCTTTTTTG 1735 chr7 ENST00000242208.4 INHBB CCGGCAAATGGATGCGGTGACAAATCTCGAGATTTGTCACCGCATCCATTTGTTTTTG 1736 chr2 ENST00000295228.3 INHBB CCGGGCTGGAACGACTGGATCATAGCTCGAGCTATGATCCAGTCGTTCCAGCTTTTTG 1737 chr2 ENST00000295228.3 INHBB CCGGTGATGAGTACAACATCGTCAACTCGAGTTGACGATGTTGTACTCATCATTTTTG 1738 chr2 ENST00000295228.3 INHBC CCGGTCAACCAGACTCGTCTTGATTCTCGAGAATCAAGACGAGTCTGGTTGATTTTTG 1739 chr12 ENST00000309668.2 INHBC CCGGCAAGACTGACATACCTGACATCTCGAGATGTCAGGTATGTCAGTCTTGTTTTTG 1740 chr12 ENST00000309668.2 INHBC CCGGCAGGCCAGTCTCATGTTCTTTCTCGAGAAAGAACATGAGACTGGCCTGTTTTTG 1741 chr12 ENST00000309668.2 INHBE CCGGCTCCTCTACCTGGATCATAATCTCGAGATTATGATCCAGGTAGAGGAGTTTTTG 1742 chr12 ENST00000266646.2 INHBE CCGGACCTGGGCTGGCATACCTTAACTCGAGTTAAGGTATGCCAGCCCAGGTTTTTTG 1743 chr12 ENST00000266646.2 INHBE CCGGGCAGCCCTTCCTAGAGCTTAACTCGAGTTAAGCTCTAGGAAGGGCTGCTTTTTG 1744 chr12 ENST00000266646.2 ITGA4 CCGGCCAACGCTTCAGTGATCAATCCTCGAGGATTGATCACTGAAGCGTTGGTTTTTG 1745 chr2 ENST00000397033.6 ITGA4 CCGGTGTAGAACACATCAAGCATTTCTCGAGAAATGCTTGATGTGTTCTACATTTTTG 1746 chr2 ENST00000397033.6 ITGA4 CCGGCATGATCTTGTGACATATTATCTCGAGATAATATGTCACAAGATCATGTTTTTG 1747 chr2 ENST00000397033.6 ITGAV CCGGTTGAAGTGTACCCTAGCATTTCTCGAGAAATGCTAGGGTACACTTCAATTTTTG 1748 chr2 ENST00000261023.7 ITGAV CCGGCACTCCAAGAACATGACTATTCTCGAGAATAGTCATGTTCTTGGAGTGTTTTTG 1749 chr2 ENST00000261023.7 ITGAV CCGGGTGAGGTCGAAACAGGATAAACTCGAGTTTATCCTGTTTCGACCTCACTTTTTG 1750 chr2 ENST00000261023.7 ITGB1 CCGGTTTGTAGGAAGAGGGATAATACTCGAGTATTATCCCTCTTCCTACAAATTTTTG 1751 chr10 ENST00000302278.7 ITGB1 CCGGGCCTTGCATTACTGCTGATATCTCGAGATATCAGCAGTAATGCAAGGCTTTTTG 1752 chr10 ENST00000302278.7 ITGB1 CCGGGCCTTGCATTACTGCTGATATCTCGAGATATCAGCAGTAATGCAAGGCTTTTTG 1753 chr10 ENST00000302278.7 ITGB3 CCGGGTCGTCAGATTCCAGTACTATCTCGAGATAGTACTGGAATCTGACGACTTTTTG 1754 chr17 ENST00000559488.5 ITGB3 CCGGGTCGTCAGATTCCAGTACTATCTCGAGATAGTACTGGAATCTGACGACTTTTTG 1755 chr17 ENST00000559488.5 ITGB3 CCGGCCACGTCTACCTTCACCAATACTCGAGTATTGGTGAAGGTAGACGTGGTTTTTG 1756 chr17 ENST00000559488.5 KIT CCGGACTTCATCTAACGAGATTAAACTCGAGTTTAATCTCGTTAGATGAAGTTTTTTG 1757 chr4 ENST00000288135.5 KIT CCGGGCGACGAGATTAGGCTGTTATCTCGAGATAACAGCCTAATCTCGTCGCTTTTTG 1758 chr4 ENST00000288135.5 KIT CCGGACGAGTTGGCCCTAGACTTAGCTCGAGCTAAGTCTAGGGCCAACTCGTTTTTTG 1759 chr4 ENST00000288135.5 KITLG CCGGGCAGGAATCGTGTGACTAATACTCGAGTATTAGTCACACGATTCCTGCTTTTTG 1760 chr12 ENST00000228280.9 KITLG CCGGGCAGGAATCGTGTGACTAATACTCGAGTATTAGTCACACGATTCCTGCTTTTTG 1761 chr12 ENST00000228280.9 KITLG CCGGCCTATTTAATCCTCTCGTCAACTCGAGTTGACGAGAGGATTAAATAGGTTTTTG 1762 chr12 ENST00000228280.9 KLHL20 CCGGGCCAATACATGGAGGTTATATCTCGAGATATAACCTCCATGTATTGGCTTTTTG 1763 chr1 ENST00000209884.4 KLHL20 CCGGGCCGCAAGAACGACCACTAATCTCGAGATTAGTGGTCGTTCTTGCGGCTTTTTG 1764 chr1 ENST00000209884.4 KLHL20 CCGGCACATTGTGAATCCCATATTTCTCGAGAAATATGGGATTCACAATGTGTTTTTG 1765 chr1 ENST00000209884.4 LEFTY1 CCGGACAAGTTACCTCACCTAATTTCTCGAGAAATTAGGTGAGGTAACTTGTTTTTTG 1766 chr1 ENST00000272134.5 LEFTY1 CCGGAGCCCAATGTGTCATTGTTTACTCGAGTAAACAATGACACATTGGGCTTTTTTG 1767 chr1 ENST00000272134.5 LEFTY1 CCGGTCTCTAGTGAGCCCTGAATTTCTCGAGAAATTCAGGGCTCACTAGAGATTTTTG 1768 chr1 ENST00000272134.5 LEFTY2 CCGGAGTTACTCCATCCCAATTTAGCTCGAGCTAAATTGGGATGGAGTAACTTTTTTG 1769 chr1 ENST00000366820.9 LEFTY2 CCGGCTAAGCACTTACGTGAGTAAACTCGAGTTTACTCACGTAAGTGCTTAGTTTTTG 1770 chr1 ENST00000366820.9 LEFTY2 CCGGTAGGCGCCTGGTGTATCCATTCTCGAGAATGGATACACCAGGCGCCTATTTTTG 1771 chr1 ENST00000366820.9 LIF CCGGGCAGTGCCAATGCCCTCTTTACTCGAGTAAAGAGGGCATTGGCACTGCTTTTTG 1772 chr22 ENST00000249075.3 LIF CCGGACCGCATAGTCGTGTACCTTGCTCGAGCAAGGTACACGACTATGCGGTTTTTTG 1773 chr22 ENST00000249075.3 LIF CCGGCAACAACCTGGACAAGCTATGCTCGAGCATAGCTTGTCCAGGTTGTTGTTTTTG 1774 chr22 ENST00000249075.3 LIFR CCGGTGACTTGCGACTACGTCATTACTCGAGTAATGACGTAGTCGCAAGTCATTTTTG 1775 chr5 ENST00000263409.8 LIFR CCGGACTTCTGCAGATTCGATATTACTCGAGTAATATCGAATCTGCAGAAGTTTTTTG 1776 chr5 ENST00000263409.8 LIFR CCGGGTAGGCTCAGACATAACATTTCTCGAGAAATGTTATGTCTGAGCCTACTTTTTG 1777 chr5 ENST00000263409.8 LTA CCGGGCCCTAGTACTGTCTTCTTTGCTCGAGCAAAGAAGACAGTACTAGGGCTTTTTG 1778 chr6 ENST00000418386.2 LTA CCGGGATCAAGTCACCGGAGCTTTCCTCGAGGAAAGCTCCGGTGACTTGATCTTTTTG 1779 chr6 ENST00000418386.2 LTA CCGGGCTCCCAGAAGATGGTGTATCCTCGAGGATACACCATCTTCTGGGAGCTTTTTG 1780 chr6 ENST00000418386.2 LTB CCGGGCGAGAGGGAAGACCTTCTTTCTCGAGAAAGAAGGTCTTCCCTCTCGCTTTTTG 1781 chr6 ENST00000429299.2 LTB CCGGCGAGAGGGTGTACGTCAACATCTCGAGATGTTGACGTACACCCTCTCGTTTTTG 1782 chr6 ENST00000429299.2 LTB CCGGGACGAAGGAACAGGCGTTTCTCTCGAGAGAAACGCCTGTTCCTTCGTCTTTTTG 1783 chr6 ENST00000429299.2 LTBP1 CCGGGATGACCTGTGTCGATGTAAACTCGAGTTTACATCGACACAGGTCATCTTTTTG 1784 chr2 ENST00000407925.5 LTBP1 CCGGGGTGGAACAGTGCTGTTATTTCTCGAGAAATAACAGCACTGTTCCACCTTTTTG 1785 chr2 ENST00000407925.5 LTBP1 CCGGCCGTTGAATACCGCCTTGAATCTCGAGATTCAAGGCGGTATTCAACGGTTTTTG 1786 chr2 ENST00000407925.5 LTBP3 CCGGGCATCCTCAATGGATGTGAAACTCGAGTTTCACATCCATTGAGGATGCTTTTTG 1787 chr11 ENST00000322147.8 LTBP3 CCGGTGTTGTTCGGGTCGGAGATTTCTCGAGAAATCTCCGACCCGAACAACATTTTTG 1788 chr11 ENST00000322147.8 LTBP3 CCGGAGCGCTTCAAGGTGGTCTTTGCTCGAGCAAAGACCACCTTGAAGCGCTTTTTTG 1789 chr11 ENST00000322147.8 LTBP4 CCGGGCTTCGACATGCCAGACTTTGCTCGAGCAAAGTCTGGCATGTCGAAGCTTTTTG 1790 chr19 ENST00000308370.11 LTBP4 CCGGTGAAACACTACAGGGTGTATGCTCGAGCATACACCCTGTAGTGTTTCATTTTTG 1791 chr19 ENST00000308370.11 LTBP4 CCGGCAACCGGCTTTGAAAGAGTTACTCGAGTAACTCTTTCAAAGCCGGTTGTTTTTG 1792 chr19 ENST00000308370.11 MAF CCGGTCAGTGGGATACGCCACATTTCTCGAGAAATGTGGCGTATCCCACTGATTTTTG 1793 chr16 ENST00000326043.4 MAF CCGGTTTATGGTGTGTGCAAGTAAACTCGAGTTTACTTGCACACACCATAAATTTTTG 1794 chr16 ENST00000326043.4 MAF CCGGGTTAGAGAAGAAGGCTATTAACTCGAGTTAATAGCCTTCTTCTCTAACTTTTTG 1795 chr16 ENST00000326043.4

MAF CCGGTGTTAATGACTTCGATCTGATCTCGAGATCAGATCGAAGTCATTAACATTTTTG 1796 chr16 ENST00000326043.4 MIF CCGGCTACATCAACTATTACGACATCTCGAGATGTCGTAATAGTTGATGTAGTTTTTG 1797 chr22 ENST00000215754.7 MIF CCGGCTACATCAACTATTACGACATCTCGAGATGTCGTAATAGTTGATGTAGTTTTTG 1798 chr22 ENST00000215754.7 MIF CCGGGACAGGGTCTACATCAACTATCTCGAGATAGTTGATGTAGACCCTGTCTTTTTG 1799 chr22 ENST00000215754.7 MINOS1- CCGGGCCAAGCTGCACAATTTAATACTCGAGTATTAAATTGTGCAGCTTGGCTTTTTG 1800 chr1 ENST00000602662.1 MINOS1- CCGGGCTGGCACTGTTCCCAGATAACTCGAGTTATCTGGGAACAGTGCCAGCTTTTTG 1801 chr1 ENST00000602662.1 MINOS1- CCGGAGAAAGACCACTGGCAGAAACCTCGAGGTTTCTGCCAGTGGTCTTTCTTTTTTG 1802 chr1 ENST00000602662.1 MSTN CCGGAGGCCCAACTATGGATATATTCTCGAGAATATATCCATAGTTGGGCCTTTTTTG 1803 chr2 ENST00000260950.4 MSTN CCGGGAGCTAGAAGGAGATCAAATTCTCGAGAATTTGATCTCCTTCTAGCTCTTTTTG 1804 chr2 ENST00000260950.4 MSTN CCGGGTATGCTTTAAAGTCTATTTCCTCGAGGAAATAGACTTTAAAGCATACTTTTTG 1805 chr2 ENST00000260950.4 NAMPT CCGGAGCGATAGCTATGACATTTATCTCGAGATAAATGTCATAGCTATCGCTTTTTTG 1806 chr7 ENST00000222553.7 NAMPT CCGGGTGAAGATCTAAGACATTTAACTCGAGTTAAATGTCTTAGATCTTCACTTTTTG 1807 chr7 ENST00000222553.7 NAMPT CCGGTACAAGGTTACTCACTATAAACTCGAGTTTATAGTGAGTAACCTTGTATTTTTG 1808 chr7 ENST00000222553.7 NBL1 CCGGGCCAAGCTGCACAATTTAATACTCGAGTATTAAATTGTGCAGCTTGGCTTTTTG 1809 chr1 ENST00000375136.7 NBL1 CCGGGCTGGCACTGTTCCCAGATAACTCGAGTTATCTGGGAACAGTGCCAGCTTTTTG 1810 chr1 ENST00000375136.7 NBL1 CCGGAGAAAGACCACTGGCAGAAACCTCGAGGTTTCTGCCAGTGGTCTTTCTTTTTTG 1811 chr1 ENST00000375136.7 NDP CCGGCTGCTAAAGGTTACCGATTTCCTCGAGGAAATCGGTAACCTTTAGCAGTTTTTG 1812 chrX ENST00000378062.5 NDP CCGGCTCTGCATATTCTAGTAATAACTCGAGTTATTACTAGAATATGCAGAGTTTTTG 1813 chrX ENST00000378062.5 NDP CCGGACGGACAGCTCATTCATAATGCTCGAGCATTATGAATGAGCTGTCCGTTTTTTG 1814 chrX ENST00000378062.5 NLRP7 CCGGCCGTTCAAGGAAATTTCTATTCTCGAGAATAGAAATTTCCTTGAACGGTTTTTG 1815 chr19 ENST00000328092.9 NLRP7 CCGGCGGGTCTCTAAGATGTCTTATCTCGAGATAAGACATCTTAGAGACCCGTTTTTG 1816 chr19 ENST00000328092.9 NLRP7 CCGGACCTGCTCAGAAATCATAAATCTCGAGATTTATGATTTCTGAGCAGGTTTTTTG 1817 chr19 ENST00000328092.9 NODAL CCGGGTGCTCCTAGATCACCATAAACTCGAGTTTATGGTGATCTAGGAGCACTTTTTG 1818 chr10 ENST00000287139.7 NODAL CCGGCACCTATAGCTTTCATGTATTCTCGAGAATACATGAAAGCTATAGGTGTTTTTG 1819 chr10 ENST00000287139.7 NODAL CCGGGCATGCTGTATGTGGATAATGCTCGAGCATTATCCACATACAGCATGCTTTTTG 1820 chr10 ENST00000287139.7 NOG CCGGAGGTCAGTATTATACGTTAAACTCGAGTTTAACGTATAATACTGACCTTTTTTG 1821 chr17 ENST00000332822.4 NOG CCGGATTCTGGTTGTTGCTAATAATCTCGAGATTATTAGCAACAACCAGAATTTTTTG 1822 chr17 ENST00000332822.4 NOG CCGGTGCGGAGGAAGTTACAGATGTCTCGAGACATCTGTAACTTCCTCCGCATTTTTG 1823 chr17 ENST00000332822.4 NRG1 CCGGGATATCACAGAGGCCTATAACCTCGAGGTTATAGGCCTCTGTGATATCTTTTTG 1824 chr8 ENST00000287842.7 NRG1 CCGGGGCTGATTCTGGAGAGTATATCTCGAGATATACTCTCCAGAATCAGCCTTTTTG 1825 chr8 ENST00000287842.7 NRG1 CCGGGACAGTGCCTCTGCCAATATCCTCGAGGATATTGGCAGAGGCACTGTCTTTTTG 1826 chr8 ENST00000287842.7 NRP1 CCGGTATACTAGAATCACCGCATTTCTCGAGAAATGCGGTGATTCTAGTATATTTTTG 1827 chr10 ENST00000265371.8 NRP1 CCGGCAGCCTTGAATGCACTTATATCTCGAGATATAAGTGCATTCAAGGCTGTTTTTG 1828 chr10 ENST00000265371.8 NRP1 CCGGCAGCCTTGAATGCACTTATATCTCGAGATATAAGTGCATTCAAGGCTGTTTTTG 1829 chr10 ENST00000265371.8 NRP2 CCGGCGACTGCAAGTATGACTTTATCTCGAGATAAAGTCATACTTGCAGTCGTTTTTG 1830 chr2 ENST00000357785.9 NRP2 CCGGCCGGATTGCTAATGAACAGATCTCGAGATCTGTTCATTAGCAATCCGGTTTTTG 1831 chr2 ENST00000357785.9 NRP2 CCGGCCTCAACTTCAACCCTCACTTCTCGAGAAGTGAGGGTTGAAGTTGAGGTTTTTG 1832 chr2 ENST00000357785.9 OSM CCGGACTTCCTCCTTTCCGTGTTTCCTCGAGGAAACACGGAAAGGAGGAAGTTTTTTG 1833 chr22 ENST00000215781.2 OSM CCGGGGACCGACTTTCCATTGATTCCTCGAGGAATCAATGGAAAGTCGGTCCTTTTTG 1834 chr22 ENST00000215781.2 OSM CCGGTGGTCCTTGCACTCCTGTTTCCTCGAGGAAACAGGAGTGCAAGGACCATTTTTG 1835 chr22 ENST00000215781.2 OSMR CCGGTAACCTGACTCATCGAGTTTACTCGAGTAAACTCGATGAGTCAGGTTATTTTTG 1836 chr5 ENST00000274276.7 OSMR CCGGAGGAGAACCCTCACCTAATAACTCGAGTTATTAGGTGAGGGTTCTCCTTTTTTG 1837 chr5 ENST00000274276.7 OSMR CCGGGCACTCCATAAGGAATAATTTCTCGAGAAATTATTCCTTATGGAGTGCTTTTTG 1838 chr5 ENST00000274276.7 PARK7 CCGGGTAGCCGTGATGTGGTCATTTCTCGAGAAATGACCACATCACGGCTACTTTTTG 1839 chr1 ENST00000338639.9 PARK7 CCGGGCAATTGTTGAAGCCCTGAATCTCGAGATTCAGGGCTTCAACAATTGCTTTTTG 1840 chr1 ENST00000338639.9 PARK7 CCGGACTCTGAGAATCGTGTGGAAACTCGAGTTTCCACACGATTCTCAGAGTTTTTTG 1841 chr1 ENST00000338639.9 PDPN CCGGGCCTCTGGTATGAGAAATAAACTCGAGTTTATTTCTCATACCAGAGGCTTTTTG 1842 chr1 ENST00000294489.10 PDPN CCGGAGTCCACGCGCAAGAACAAAGCTCGAGCTTTGTTCTTGCGCGTGGACTTTTTTG 1843 chr1 ENST00000294489.10 PDPN CCGGTGACCCTGGTTGGAATCATAGCTCGAGCTATGATTCCAACCAGGGTCATTTTTG 1844 chr1 ENST00000294489.10 PF4 CCGGACGCTGAAGAATGGAAGGAAACTCGAGTTTCCTTCCATTCTTCAGCGTTTTTTG 1845 chr4 ENST00000296029.3 PF4 CCGGCCAACTGATAGCCACGCTGAACTCGAGTTCAGCGTGGCTATCAGTTGGTTTTTG 1846 chr4 ENST00000296029.3 PF4 CCGGCACGCTGAAGAATGGAAGGAACTCGAGTTCCTTCCATTCTTCAGCGTGTTTTTG 1847 chr4 ENST00000296029.3 PF4V1 CCGGGTTGTGGTATAGTCAATCTATCTCGAGATAGATTGACTATACCACAACTTTTTG 1848 chr4 ENST00000226524.3 PF4V1 CCGGAGCTGCCTAAGTGTGCACTTTCTCGAGAAAGTGCACACTTAGGCAGCTTTTTTG 1849 chr4 ENST00000226524.3 PF4V1 CCGGCTGACACATCACAATTTCATACTCGAGTATGAAATTGTGATGTGTCAGTTTTTG 1850 chr4 ENST00000226524.3 PGLYRP1 CCGGGTGCCCACTCAGGTCACTTATCTCGAGATAAGTGACCTGAGTGGGCACTTTTTG 1851 chr19 ENST00000008938.4 PGLYRP1 CCGGCTTACGCTATGTGGTGGTATCCTCGAGGATACCACCACATAGCGTAAGTTTTTG 1852 chr19 ENST00000008938.4 PGLYRP1 CCGGCATCAGCTTCATGGGCAACTACTCGAGTAGTTGCCCATGAAGCTGATGTTTTTG 1853 chr19 ENST00000008938.4 PLP2 CCGGCCTGTCGGTGATTGAGATGATCTCGAGATCATCTCAATCACCGACAGGTTTTTG 1854 chrX ENST00000376327.5 PLP2 CCGGCCTGTCGGTGATTGAGATGATCTCGAGATCATCTCAATCACCGACAGGTTTTTG 1855 chrX ENST00000376327.5 PLP2 CCGGCGAAAGGGAATCCTCCTGTTTCTCGAGAAACAGGAGGATTCCCTTTCGTTTTTG 1856 chrX ENST00000376327.5 PPBP CCGGAGGTGATGAATCTGCTGATTACTCGAGTAATCAGCAGATTCATCACCTTTTTTG 1857 chr4 ENST00000296028.3 PPBP CCGGTGTTTCTGCCAAACTTCTTTACTCGAGTAAAGAAGTTTGGCAGAAACATTTTTG 1858 chr4 ENST00000296028.3 PPBP CCGGCTCCCAGGAAGGGTAGAATTTCTCGAGAAATTCTACCCTTCCTGGGAGTTTTTG 1859 chr4 ENST00000296028.3 PXDN CCGGAGATTGCGACTGGACTCAAACCTCGAGGTTTGAGTCCAGTCGCAATCTTTTTTG 1860 chr2 ENST00000252804.8 PXDN CCGGGTTCCTGACGTCAGTCGAAATCTCGAGATTTCGACTGACGTCAGGAACTTTTTG 1861 chr2 ENST00000252804.8 PXDN CCGGGAAGGATTCTTGACCATCAATCTCGAGATTGATGGTCAAGAATCCTTCTTTTTG 1862 chr2 ENST00000252804.8 RORC CCGGCACCTCACAAATTGAAGTGATCTCGAGATCACTTCAATTTGTGAGGTGTTTTTG 1863 chr1 ENST00000318247.6 RORC CCGGGCCCTCATATTCCAACAACTTCTCGAGAAGTTGTTGGAATATGAGGGCTTTTTG 1864 chr1 ENST00000318247.6 RORC CCGGGCTTCTCAAAGCAGGAGCAATCTCGAGATTGCTCCTGCTTTGAGAAGCTTTTTG 1865 chr1 ENST00000318247.6 RORC CCGGCGAGGATGAGATTGCCCTCTACTCGAGTAGAGGGCAATCTCATCCTCGTTTTTG 1866 chr1 ENST00000318247.6 SCG2 CCGGACGACAAGGATCAAGAATTAGCTCGAGCTAATTCTTGATCCTTGTCGTTTTTTG 1867 chr2 ENST00000305409.2 SCG2 CCGGCCTGTCTCTTATCCCTTTAATCTCGAGATTAAAGGGATAAGAGACAGGTTTTTG 1868 chr2 ENST00000305409.2 SCG2 CCGGGAAAGCAGCCCAGATTATAATCTCGAGATTATAATCTGGGCTGCTTTCTTTTTG 1869 chr2 ENST00000305409.2 SCGB3A1 CCGGTCATAGAGGGCTCCCAGAAGTCTCGAGACTTCTGGGAGCCCTCTATGATTTTTG 1870 chr5 ENST00000292641.3 SCGB3A1 CCGGCCCGTGAACCACCTCATAGAGCTCGAGCTCTATGAGGTGGTTCACGGGTTTTTG 1871 chr5 ENST00000292641.3 SCGB3A1 CCGGGACTGGAGCATCTACACCTGACTCGAGTCAGGTGTAGATGCTCCAGTCTTTTTG 1872 chr5 ENST00000292641.3 SECTM1 CCGGCACCAGAGAAATAACAGACAACTCGAGTTGTCTGTTATTTCTCTGGTGTTTTTG 1873 chr17 ENST00000269389.7 SECTM1 CCGGCCATGACTCGAATATCTGAAACTCGAGTTTCAGATATTCGAGTCATGGTTTTTG 1874 chr17 ENST00000269389.7 SECTM1 CCGGCCATGACTCGAATATCTGAAACTCGAGTTTCAGATATTCGAGTCATGGTTTTTG 1875 chr17 ENST00000269389.7 SLURP1 CCGGGTGCTTCCTGCAGGACCATTACTCGAGTAATGGTCCTGCAGGAAGCACTTTTTG 1876 chr8 ENST00000246515.1 SLURP1 CCGGAGACCTCTGCAACTCGGAACTCTCGAGAGTTCCGAGTTGCAGAGGTCTTTTTTG 1877 chr8 ENST00000246515.1 SLURP1 CCGGCTCAAGTGCTACACCTGCAAGCTCGAGCTTGCAGGTGTAGCACTTGAGTTTTTG 1878 chr8 ENST00000246515.1 SOSTDC1 CCGGGATGCCACAGAAATCCTTTATCTCGAGATAAAGGATTTCTGTGGCATCTTTTTG 1879

chr7 ENST00000307068.4 SOSTDC1 CCGGGGAACTGCGTTCCACCAAATACTCGAGTATTTGGTGGAACGCAGTTCCTTTTTG 1880 chr7 ENST00000307068.4 SOSTDC1 CCGGTGAATCTTCACAGTAACATTTCTCGAGAAATGTTACTGTGAAGATTCATTTTTG 1881 chr7 ENST00000307068.4 SP100 CCGGGAAGTGAGCCTGTGATCAATACTCGAGTATTGATCACAGGCTCACTTCTTTTTG 1882 chr2 ENST00000340126.8 SP100 CCGGTATACGCTGCGGTGGATATACCTCGAGGTATATCCACCGCAGCGTATATTTTTG 1883 chr2 ENST00000340126.8 SP100 CCGGTCGTGATCTCATCACAAATAACTCGAGTTATTTGTGATGAGATCACGATTTTTG 1884 chr2 ENST00000340126.8 SPI1 CCGGGCCCTATGACACGGATCTATACTCGAGTATAGATCCGTGTCATAGGGCTTTTTG 1885 chr11 ENST00000378538.7 SPI1 CCGGAGAGCTTCGCCGAGAACAACTCTCGAGAGTTGTTCTCGGCGAAGCTCTTTTTTG 1886 chr11 ENST00000378538.7 SPI1 CCGGCGGATCTATACCAACGCCAAACTCGAGTTTGGCGTTGGTATAGATCCGTTTTTG 1887 chr11 ENST00000378538.7 SPI1 CCGGCCGTATGTAAATCAGATCTCCCTCGAGGGAGATCTGATTTACATACGGTTTTTG 1888 chr11 ENST00000378538.7 SPP1 CCGGCCACAAGCAGTCCAGATTATACTCGAGTATAATCTGGACTGCTTGTGGTTTTTG 1889 chr4 ENST00000237623.11 SPP1 CCGGCCGAGGTGATAGTGTGGTTTACTCGAGTAAACCACACTATCACCTCGGTTTTTG 1890 chr4 ENST00000237623.11 SPP1 CCGGCTTCAGGGTTATGTCTATGTTCTCGAGAACATAGACATAACCCTGAAGTTTTTG 1891 chr4 ENST00000237623.11 TBX21 CCGGGCCCTAACTACAGTCGTTTACCTCGAGGTAAACGACTGTAGTTAGGGCTTTTTG 1892 ch17 ENSTO0000177694.1 TBX21 CCGGCCTGTTGTGGTCCAAGTTTAACTCGAGTTAAACTTGGACCACAACAGGTTTTTG 1893 ch17 ENSTO0000177694.1 TBX21 CCGGCGCTTCCAACACGCATATCTTCTCGAGAAGATATGCGTGTTGGAAGCGTTTTTG 1894 ch17 ENSTO0000177694.1 TBX21 CCGGACAATGTGACCCAGATGATTGCTCGAGCAATCATCTGGGTCACATTGTTTTTTG 1895 ch17 ENSTO0000177694.1 TCAP CCGGCTTTGTAGTTTGCCCAGAGTTCTCGAGAACTCTGGGCAAACTACAAAGTTTTTG 1896 chr17 ENST00000309889.2 TCAP CCGGGGCCATGGCTGCTTTGTAGTTCTCGAGAACTACAAAGCAGCCATGGCCTTTTTG 1897 chr17 ENST00000309889.2 TCAP CCGGGGTGGCTGAGATCACAAAGCACTCGAGTGCTTTGTGATCTCAGCCACCTTTTTG 1898 chr17 ENST00000309889.2 TGFB1 CCGGACTGCGGATCTCTGTGTCATTCTCGAGAATGACACAGAGATCCGCAGTTTTTTG 1899 chr19 ENST00000221930.5 TGFB1 CCGGCCACAACGAAATCTATGACAACTCGAGTTGTCATAGATTTCGTTGTGGTTTTTG 1900 chr19 ENST00000221930.5 TGFB1 CCGGCCACAACGAAATCTATGACAACTCGAGTTGTCATAGATTTCGTTGTGGTTTTTG 1901 chr19 ENST00000221930.5 TGFB2 CCGGGCGGCCTATTGCTTTAGAAATCTCGAGATTTCTAAAGCAATAGGCCGCTTTTTG 1902 chr1 ENST00000366930.8 TGFB2 CCGGGCTGGAGCATGCCCGTATTTACTCGAGTAAATACGGGCATGCTCCAGCTTTTTG 1903 chr1 ENST00000366930.8 TGFB2 CCGGTTGCTGCCTACGTCCACTTTACTCGAGTAAAGTGGACGTAGGCAGCAATTTTTG 1904 chr1 ENST00000366930.8 TGFB3 CCGGCATTGCCAAACAGCGCTATATCTCGAGATATAGCGCTGTTTGGCAATGTTTTTG 1905 chr14 ENST00000238682.7 TGFB3 CCGGGCTCTAGGGAATCTGGATTATCTCGAGATAATCCAGATTCCCTAGAGCTTTTTG 1906 chr14 ENST00000238682.7 TGFB3 CCGGCGGAATACTATGCCAAAGAAACTCGAGTTTCTTTGGCATAGTATTCCGTTTTTG 1907 chr14 ENST00000238682.7 TGFBR1 CCGGGCCTTGAGAGTAATGGCTAAACTCGAGTTTAGCCATTACTCTCAAGGCTTTTTG 1908 chr9 ENST00000374994.8 TGFBR1 CCGGCTCATGTTGATGGTCTATATCCTCGAGGATATAGACCATCAACATGAGTTTTTG 1909 chr9 ENST00000374994.8 TGFBR1 CCGGGAAGTTGCTGTTAAGATATTCCTCGAGGAATATCTTAACAGCAACTTCTTTTTG 1910 chr9 ENST00000374994.8 TGFBR2 CCGGCGTTCAGAAGTCGGTTAATAACTCGAGTTATTAACCGACTTCTGAACGTTTTTG 1911 chr3 ENST00000295754.9 TGFBR2 CCGGCTCTAGGCTTTATCGTGTTTACTCGAGTAAACACGATAAAGCCTAGAGTTTTTG 1912 chr3 ENST00000295754.9 TGFBR2 CCGGCTCAGGAAATGAGATTGATTTCTCGAGAAATCAATCTCATTTCCTGAGTTTTTG 1913 chr3 ENST00000295754.9 TGFBR3 CCGGGGAGTTGGTAAAGGGTTAATACTCGAGTATTAACCCTTTACCAACTCCTTTTTG 1914 chr1 ENST00000212355.8 TGFBR3 CCGGTAATGGATTTCCGGGAGATATCTCGAGATATCTCCCGGAAATCCATTATTTTTG 1915 chr1 ENST00000212355.8 TGFBR3 CCGGCACACCCAGGGCTAGTATAAACTCGAGTTTATACTAGCCCTGGGTGTGTTTTTG 1916 chr1 ENST00000212355.8 THBS1 CCGGGTAGGTTATGATGAGTTTAATCTCGAGATTAAACTCATCATAACCTACTTTTTG 1917 chr15 ENST00000260356.5 THBS1 CCGGCGTGACTGTAAGATTGTAAATCTCGAGATTTACAATCTTACAGTCACGTTTTTG 1918 chr15 ENST00000260356.5 THBS1 CCGGGAGATCCCTAATCATCAAATTCTCGAGAATTTGATGATTAGGGATCTCTTTTTG 1919 chr15 ENST00000260356.5 THNSL2 CCGGGAGCCGATCAAGACTGTGTTTCTCGAGAAACACAGTCTTGATCGGCTCTTTTTG 1920 chr2 ENST00000324166.6 THNSL2 CCGGGCTGCCATTGAGAGTGTTCAACTCGAGTTGAACACTCTCAATGGCAGCTTTTTG 1921 chr2 ENST00000324166.6 THNSL2 CCGGGCTGCCATTGAGAGTGTTCAACTCGAGTTGAACACTCTCAATGGCAGCTTTTTG 1922 chr2 ENST00000324166.6 THPO CCGGGACCTCCGAGTCCTCAGTAAACTCGAGTTTACTGAGGACTCGGAGGTCTTTTTG 1923 chr3 ENST00000204615.11 THPO CCGGAGCTAGCTCTTTGGTCTATTTCTCGAGAAATAGACCAAAGAGCTAGCTTTTTTG 1924 chr3 ENST00000204615.11 THPO CCGGCAACCTCCAGCCTGGATATTCCTCGAGGAATATCCAGGCTGGAGGTTGTTTTTG 1925 chr3 ENST00000204615.11 TIMP1 CCGGGCACAGTGTTTCCCTGTTTATCTCGAGATAAACAGGGAAACACTGTGCTTTTTG 1926 chrX ENST00000218388.8 TIMP1 CCGGGCACAGTGTTTCCCTGTTTATCTCGAGATAAACAGGGAAACACTGTGCTTTTTG 1927 chrX ENST00000218388.8 TIMP1 CCGGACAGACGGCCTTCTGCAATTCCTCGAGGAATTGCAGAAGGCCGTCTGTTTTTTG 1928 chrX ENST00000218388.8 TNF CCGGGAACCCAAGCTTAGAACTTTACTCGAGTAAAGTTCTAAGCTTGGGTTCTTTTTG 1929 chr6 ENST00000449264.2 TNF CCGGGGAGCCAGCTCCCTCTATTTACTCGAGTAAATAGAGGGAGCTGGCTCCTTTTTG 1930 chr6 ENST00000449264.2 TNF CCGGTGGCGTGGAGCTGAGAGATAACTCGAGTTATCTCTCAGCTCCACGCCATTTTTG 1931 chr6 ENST00000449264.2 TNFRSF4 CCGGGCACGTGGTGTAACCTCAGAACTCGAGTTCTGAGGTTACACCACGTGCTTTTTG 1932 chrl ENST00000379236.3 TNFRSF4 CCGGCAGCAATAGCTCGGACGCAATCTCGAGATTGCGTCCGAGCTATTGCTGTTTTTG 1933 chr1 ENST00000379236.3 TNFRSF4 CCGGGACAGCTACAAGCCTGGAGTTCTCGAGAACTCCAGGCTTGTAGCTGTCTTTTTG 1934 chr1 ENST00000379236.3 TNFRSF4 CCGGGCTTCTACAACGACGTGGTCACTCGAGTGACCACGTCGTTGTAGAAGCTTTTTG 1935 chr1 ENST00000379236.3 TNFRSF11 CCGGTGTTTACTTGCCCGGTTTAATCTCGAGATTAAACCGGGCAAGTAAACATTTTTG 1936 chr18 ENST00000586569.2 TNFRSF11 CCGGTGTACCAGTGAGAAGCATTATCTCGAGATAATGCTTCTCACTGGTACATTTTTG 1937 chr18 ENST00000586569.2 TNFRSF11 CCGGTGGGACGGTGCTGTAACAAATCTCGAGATTTGTTACAGCACCGTCCCATTTTTG 1938 chr18 ENST00000586569.2 TNFRSF11 CCGGGAAAGCACTCACAGCTAATTTCTCGAGAAATTAGCTGTGAGTGCTTTCTTTTTG 1939 chr8 ENST00000297350.8 TNFRSF11 CCGGGATAAATGCTTGCTGCATAAACTCGAGTTTATGCAGCAAGCATTTATCTTTTTG 1940 chr8 ENST00000297350.8 TNFRSF11 CCGGCCAGTGTGTGTTCATTGTAAACTCGAGTTTACAATGAACACACACTGGTTTTTG 1941 chr8 ENST00000297350.8 TNFRSF1A CCGGAGAACCAGTACCGGCATTATTCTCGAGAATAATGCCGGTACTGGTTCTTTTTTG 1942 chr12 ENST00000162749.6 TNFRSF1A CCGGGGAGCTGTTGGTGGGAATATACTCGAGTATATTCCCACCAACAGCTCCTTTTTG 1943 chr12 ENST00000162749.6 TNFRSF1A CCGGCTTGAAGGAACTACTACTAAGCTCGAGCTTAGTAGTAGTTCCTTCAAGTTTTTG 1944 chr12 ENST00000162749.6 TNFRSF9 CCGGGCTCCGTTTCTCTGTTGTTAACTCGAGTTAACAACAGAGAAACGGAGCTTTTTG 1945 chrl ENST00000377507.7 TNFRSF9 CCGGCAAGAACACCATCCTACATAACTCGAGTTATGTAGGATGGTGTTCTTGTTTTTG 1946 chrl ENST00000377507.7 TNFRSF9 CCGGCAGTCCCTGTCCTCCAAATAGCTCGAGCTATTTGGAGGACAGGGACTGTTTTTG 1947 chrl ENST00000377507.7 TNFSF9 CCGGCAAGTTGGACCTTGATATTTACTCGAGTAAATATCAAGGTCCAACTTGTTTTTG 1948 chr19 ENST00000245817.4 TNFSF9 CCGGCTACTATGTCTTCTTTCAACTCTCGAGAGTTGAAAGAAGACATAGTAGTTTTTG 1949 chr19 ENST00000245817.4 TNFSF9 CCGGCCCTTCACCGAGGTCGGAATACTCGAGTATTCCGACCTCGGTGAAGGGTTTTTG 1950 chr19 ENST00000245817.4 TNFSF9 CCGGTGAGCTACAAAGAGGACACGACTCGAGTCGTGTCCTCTTTGTAGCTCATTTTTG 1951 chr19 ENST00000245817.4 TNFSF10 CCGGAGAAATAGTTGTTGGTCTAAACTCGAGTTTAGACCAACAACTATTTCTTTTTTG 1952 chr3 ENST00000241261.6 TNFSF10 CCGGAGTTATCCTGACCCTATATTGCTCGAGCAATATAGGGTCAGGATAACTTTTTTG 1953 chr3 ENST00000241261.6 TNFSF10 CCGGGACAAACAAATGGTCCAATATCTCGAGATATTGGACCATTTGTTTGTCTTTTTG 1954 chr3 ENST00000241261.6 TNFSF11 CCGGCTAATGGTGTACGTCACTAAACTCGAGTTTAGTGACGTACACCATTAGTTTTTG 1955 chr13 ENST00000398795.6 TNFSF11 CCGGCCGGATCAGGATGCAACATACCTCGAGGTATGTTGCATCCTGATCCGGTTTTTG 1956 chr13 ENST00000398795.6 TNFSF11 CCGGGCAGTATATTTCTTCGTTCTTCTCGAGAAGAACGAAGAAATATACTGCTTTTTG 1957 chr13 ENST00000398795.6 TNFSF12 CCGGGTATTCCCACTCTTATCTTACCTCGAGGTAAGATAAGAGTGGGAATACTTTTTG 1958 chr17 ENST00000293825.10 TNFSF12 CCGGGGGCATTGTGTTCACTGTACTCTCGAGAGTACAGTGAACACAATGCCCTTTTTG 1959 chr17 ENST00000293825.10 TNFSF12 CCGGCAGATGGAGGTTACACAACTTCTCGAGAAGTTGTGTAACCTCCATCTGTTTTTG 1960 chr17 ENST00000293825.10 TNFSF12- CCGGCCTCACCTACTTCGGACTCTTCTCGAGAAGAGTCCGAAGTAGGTGAGGTTTTTG 1961 chr17 ENST00000293826.4 TNFSF12- CCGGCTGTACTGTCAGGTGCACTTTCTCGAGAAAGTGCACCTGACAGTACAGTTTTTG 1962 chr17 ENST00000293826.4

TNFSF12- CCGGGCGCAGGCAGATGGAGGTTACCTCGAGGTAACCTCCATCTGCCTGCGCTTTTTG 1963 chr17 ENST00000293826.4 TNFSF13 CCGGCAGTTGCCCTCTGGTTGAGTTCTCGAGAACTCAACCAGAGGGCAACTGTTTTTG 1964 chr17 ENST00000338784.8 TNFSF13 CCGGATGGCTCTGCTGACCCAACAACTCGAGTTGTTGGGTCAGCAGAGCCATTTTTTG 1965 chr17 ENST00000338784.8 TNFSF13 CCGGCCCAACAAACAGAGCTGCAGACTCGAGTCTGCAGCTCTGTTTGTTGGGTTTTTG 1966 chr17 ENST00000338784.8 TNFSF13B CCGGCCTGAAACACTACCCAATAATCTCGAGATTATTGGGTAGTGTTTCAGGTTTTTG 1967 chr13 ENST00000375887.8 TNFSF13B CCGGCTACGCCATGGGACATCTAATCTCGAGATTAGATGTCCCATGGCGTAGTTTTTG 1968 chr13 ENST00000375887.8 TNFSF13B CCGGGTGACTTTGTTTCGATGTATTCTCGAGAATACATCGAAACAAAGTCACTTTTTG 1969 chr13 ENST00000375887.8 TNFSF14 CCGGTCCTGGGAGCAGCTGATACAACTCGAGTTGTATCAGCTGCTCCCAGGATTTTTG 1970 chr19 ENST00000599359.1 TNFSF14 CCGGGACAGACCGACATCCCATTCACTCGAGTGAATGGGATGTCGGTCTGTCTTTTTG 1971 chr19 ENST00000599359.1 TNFSF14 CCGGATGGGTCTGACACGTGGAGAACTCGAGTTCTCCACGTGTCAGACCCATTTTTTG 1972 chr19 ENST00000599359.1 TNFSF15 CCGGATTAAGACACTGATCACTAAACTCGAGTTTAGTGATCAGTGTCTTAATTTTTTG 1973 chr9 ENST00000374045.4 TNFSF15 CCGGGTCGGGAGACTACTTCATTTACTCGAGTAAATGAAGTAGTCTCCCGACTTTTTG 1974 chr9 ENST00000374045.4 TNFSF15 CCGGACTATAGGAGGAGAGCAAATACTCGAGTATTTGCTCTCCTCCTATAGTTTTTTG 1975 chr9 ENST00000374045.4 TNFSF18 CCGGCCTTCAGTTGGCTAATCTTTACTCGAGTAAAGATTAGCCAACTGAAGGTTTTTG 1976 chr1 ENST00000404377.3 TNFSF18 CCGGCTGAACCTCCTTGCGTGAATACTCGAGTATTCACGCAAGGAGGTTCAGTTTTTG 1977 chr1 ENST00000404377.3 TNFSF18 CCGGATGATACAAACTCTAACAAACCTCGAGGTTTGTTAGAGTTTGTATCATTTTTTG 1978 chr1 ENST00000404377.3 TNFSF4 CCGGGTGGCCTCTCTGACTTACAAACTCGAGTTTGTAAGTCAGAGAGGCCACTTTTTG 1979 chr1 ENST00000281834.3 TNFSF4 CCGGGCAGAACAACTCAGTCATCATCTCGAGATGATGACTGAGTTGTTCTGCTTTTTG 1980 chr1 ENST00000281834.3 TNFSF4 CCGGGCCAAGATTCGAGAGGAACAACTCGAGTTGTTCCTCTCGAATCTTGGCTTTTTG 1981 chr1 ENST00000281834.3 TNFSF8 CCGGACTGTATGGTCTTGATCTATTCTCGAGAATAGATCAAGACCATACAGTTTTTTG 1982 chr9 ENST00000223795.2 TNFSF8 CCGGCAAACTACACAGGGTATTAAACTCGAGTTTAATACCCTGTGTAGTTTGTTTTTG 1983 chr9 ENST00000223795.2 TNFSF8 CCGGGTGGATACATTCCAGTACATACTCGAGTATGTACTGGAATGTATCCACTTTTTG 1984 chr9 ENST00000223795.2 TNFSF9 CCGGCAAGTTGGACCTTGATATTTACTCGAGTAAATATCAAGGTCCAACTTGTTTTTG 1985 chr19 ENST00000245817.4 TNFSF9 CCGGCTACTATGTCTTCTTTCAACTCTCGAGAGTTGAAAGAAGACATAGTAGTTTTTG 1986 chr19 ENST00000245817.4 TNFSF9 CCGGCCCTTCACCGAGGTCGGAATACTCGAGTATTCCGACCTCGGTGAAGGGTTTTTG 1987 chr19 ENST00000245817.4 TRIM16 CCGGGCCGTTGTTCAGCGCAAATATCTCGAGATATTTGCGCTGAACAACGGCTTTTTG 1988 chr17 ENST00000336708.11 TRIM16 CCGGGCCGTTGTTCAGCGCAAATATCTCGAGATATTTGCGCTGAACAACGGCTTTTTG 1989 chr17 ENST00000336708.11 TRIM16 CCGGCCGCATCAGGTGAACATCAAACTCGAGTTTGATGTTCACCTGATGCGGTTTTTG 1990 chr17 ENST00000336708.11 TSLP CCGGACTCAATGATAGCACCTAAACCTCGAGGTTTAGGTGCTATCATTGAGTTTTTTG 1991 chr5 ENST00000344895.3 TSLP CCGGCGTCGCTTCAATCGACCTTTACTCGAGTAAAGGTCGATTGAAGCGACGTTTTTG 1992 chr5 ENST00000344895.3 TSLP CCGGCCATCTTTATTATGGTCATATCTCGAGATATGACCATAATAAAGATGGTTTTTG 1993 chr5 ENST00000344895.3 TWSG1 CCGGGACTGTGTTGGTATGTGTAATCTCGAGATTACACATACCAACACAGTCITTTTG 1994 chr18 ENST00000262120.9 TWSG1 CCGGGCGCCTTATTCCAGTGACAAACTCGAGTTTGTCACTGGAATAAGGCGCTTTTTG 1995 chr18 ENST00000262120.9 TWSG1 CCGGGAATCACTGAGCTGTAACAAACTCGAGTTTGTTACAGCTCAGTGATTCTTTTTG 1996 chr18 ENST00000262120.9 TXLNA CCGGGCACATACTGTGTGGACAATACTCGAGTATTGTCCACACAGTATGTGCTTTTTG 1997 chr1 ENST00000373609.1 TXLNA CCGGTGCTGATGCAGACATTGAATACTCGAGTATTCAATGTCTGCATCAGCATTTTTG 1998 chr1 ENST00000373609.1 TXLNA CCGGAGCGAGGTATTCACCACATTCCTCGAGGAATGTGGTGAATACCTCGCTTTTTTG 1999 chr1 ENST00000373609.1 VASN CCGGAGCTTGACTACGCCGACTTTGCTCGAGCAAAGTCGGCGTAGTCAAGCTTTTTTG 2000 chr16 ENST00000304735.3 VASN CCGGAGCCAACAGGCTGCATGAAATCTCGAGATTTCATGCAGCCTGTTGGCTTTTTTG 2001 chr16 ENST00000304735.3 VASN CCGGGAGATCCTTTCCCATTTATTCCTCGAGGAATAAATGGGAAAGGATCTCTTTTTG 2002 chr16 ENST00000304735.3 VEGFA CCGGCAAGATCCGCAGACGTGTAAACTCGAGTTTACACGTCTGCGGATCTTGTTTTTG 2003 chr6 ENST00000425836.6 VEGFA CCGGCAAGATCCGCAGACGTGTAAACTCGAGTTTACACGTCTGCGGATCTTGTTTTTG 2004 chr6 ENST00000425836.6 VEGFA CCGGGCGCAAGAAATCCCGGTATAACTCGAGTTATACCGGGATTTCTTGCGCTTTTTG 2005 chr6 ENST00000425836.6 VSTM1 CCGGATGAATATGCGGCACTGAAAGCTCGAGCTITCAGTGCCGCATATTCATTTTTTG 2006 chr19 ENST00000338372.6 VSTM1 CCGGCATTCCCAGAATGTGACATTTCTCGAGAAATGTCACATTCTGGGAATGTTTTTG 2007 chr19 ENST00000338372.6 VSTM1 CCGGGAGTGACCTATGCTGAGCTAACTCGAGTTAGCTCAGCATAGGTCACTCTTTTTG 2008 chr19 ENST00000338372.6 WFIKKN1 CCGGTGCGCCCTGATCAGATGTATGCTCGAGCATACATCTGATCAGGGCGCATTTTTG 2009 chr16 ENST00000319070.2 WFIKKN1 CCGGGGACGTGCTCAAGGATGACAACTCGAGTTGTCATCCTTGAGCACGTCCTTTTTG 2010 chr16 ENST00000319070.2 WFIKKN1 CCGGAGTGCTGCATCAACGTGTGTGCTCGAGCACACACGTTGATGCAGCACTTTTTTG 2011 chr16 ENST00000319070.2 WFIKKN2 CCGGTCAAGTTCTTGGGCACCAAGTCTCGAGACTTGGTGCCCAAGAACTTGATTTTTG 2012 chr17 ENST00000311378.4 WFIKKN2 CCGGTACAACCGCTGCTATATGGACCTCGAGGTCCATATAGCAGCGGTTGTATTTTTG 2013 chr17 ENST00000311378.4 WFIKKN2 CCGGCACCAGCTTGCTCAGATATTCCTCGAGGAATATCTGAGCAAGCTGGTGTTTTTG 2014 chr17 ENST00000311378.4 WNT1 CCGGCTGTCGAGAAACGGCGTTTATCTCGAGATAAACGCCGTTTCTCGACAGTTTTTG 2015 chr12 ENST00000293549.3 WNT1 CCGGGACCTCGTCTACTTCGAGAAACTCGAGTTTCTCGAAGTAGACGAGGTCTTTTTG 2016 chr12 ENST00000293549.3 WNT1 CCGGGCCACGAGTTTGGATGTTGTACTCGAGTACAACATCCAAACTCGTGGCTTTTTG 2017 chr12 ENST00000293549.3 WNT2 CCGGCCACAAATGGTCCCAATTAAGCTCGAGCTTAATTGGGACCATTTGTGGTTTTTG 2018 chr7 ENST00000265441.7 WNT2 CCGGTCGGGAATCTGCCTTTGTTTACTCGAGTAAACAAAGGCAGATTCCCGATTTTTG 2019 chr7 ENST00000265441.7 WNT2 CCGGTTGACTATGGGATCAAATTTGCTCGAGCAAATTTGATCCCATAGTCAATTTTTG 2020 chr7 ENST00000265441.7 WNT5A CCGGCTCCCAGGACCCGCTTATTTACTCGAGTAAATAAGCGGGTCCTGGGAGTTTTTG 2021 chr3 ENST00000264634.8 WNT5A CCGGCAAAGAATGCCAGTATCAATTCTCGAGAATTGATACTGGCATTCTTTGTTTTTG 2022 chr3 ENST00000264634.8 WNT5A CCGGCCTGTTCAGATGTCAGAAGTACTCGAGTACTTCTGACATCTGAACAGGTTTTTG 2023 chr3 ENST00000264634.8 WNT7A CCGGCATAGGAGAAGGCTCACAAATCTCGAGATTTGTGAGCCTTCTCCTATGTTTTTG 2024 chr3 ENST00000285018.4 WNT7A CCGGGGCGCAAGCATCATCTGTAACCTCGAGGTTACAGATGATGCTTGCGCCTTTTTG 2025 chr3 ENST00000285018.4 WNT7A CCGGTCTTCGGGAAGGAGCTCAAAGCTCGAGCTTTGAGCTCCTTCCCGAAGATTTTTG 2026 chr3 ENST00000285018.4 XCL1 CCGGGCTGTGACAATGGCAACAATTCTCGAGAATTGTTGCCATTGTCACAGCTTTTTG 2027 chr1 ENST00000367818.3 XCL1 CCGGTTCAACTTGTCTCTATAATAGCTCGAGCTATTATAGAGACAAGTTGAATTTTTG 2028 chr1 ENST00000367818.3 XCL1 CCGGAGATTCTGGCTAGTGTCTATCCTCGAGGATAGACACTAGCCAGAATCTTTTTTG 2029 chr1 ENST00000367818.3 XCL2 CCGGACTGCCAGTTAGCAGAATCAACTCGAGTTGATTCTGCTAACTGGCAGTTTTTTG 2030 chr1 ENST00000367819.2 XCL2 CCGGGTAGGGAGTGAAGTCTCACATCTCGAGATGTGAGACTTCACTCCCTACTTTTTG 2031 chr1 ENST00000367819.2 XCL2 CCGGGAAATCCAACACCAGAAATAACTCGAGTTATTTCTGGTGTTGGATTTCTTTTTG 2032 chr1 ENST00000367819.2 ZFP36 CCGGGATCCGACCCTGATGAATATGCTCGAGCATATTCATCAGGGTCGGATCTTTTTG 2033 chr19 ENST00000597629.1 ZFP36 CCGGATCTGTCTCCTAGAATCTTATCTCGAGATAAGATTCTAGGAGACAGATTTTTTG 2034 chr19 ENST00000597629.1 ZFP36 CCGGCCCTTTATTTATGACGACTTTCTCGAGAAAGTCGTCATAAATAAAGGGTTTTTG 2035 chr19 ENST00000597629.1

TABLE-US-00020 TABLE 16 3' to 5' (Reverse) shRNA sequences for Silencing of Cytokine/Chemokine Genes to Reduce the Incidence of CRS Target SEQ Gene ID Symbol shRNA Reverse Oligo Sequence NO: Location Gene ID No. A2M AATTCAAAAAAGGCGTCCCTATACCAAATAACTCGA 2036 chr12 ENST000003 GTTATTTGGTATAGGGACGCCT 18602.11 A2M AATTCAAAAAAGACTGCATCAATCGTCATAACTCGA 2037 chr12 ENST000003 GTTATGACGATTGATGCAGTCT 18602.11 A2M AATTCAAAAACCTCCAGACATCCTTGAAATACTCGA 2038 chr12 ENST000003 GTATTTCAAGGATGTCTGGAGG 18602.11 ACKR1 AATTCAAAAAATCCTGTGGGCCTGGTTTATTCTCGA 2039 chr1 ENST000003 GAATAAACCAGGCCCACAGGAT 68122.2 ACKR1 AATTCAAAAATGGCAGAAGCCCTGGCAATTTCTCGA 2040 chr1 ENST000003 GAAATTGCCAGGGCTTCTGCCA 68122.2 ACKR1 AATTCAAAAAGGCGGATGGTTGAGATCTATCCTCGA 2041 chr1 ENST000003 GGATAGATCTCAACCATCCGCC 68122.2 ACKR2 AATTCAAAAAGAGCACTCTTTATACTATTAACTCGA 2042 chr3 ENST000004 GTTAATAGTATAAAGAGTGCTC 22265.5 ACKR2 AATTCAAAAAGTGGAACTGCCACGCAGATTTCTCGA 2043 chr3 ENST000004 GAAATCTGCGTGGCAGTTCCAC 22265.5 ACKR2 AATTCAAAAACATTGGGTCTTCGGGAGTTTCCTCGA 2044 chr3 ENST000004 GGAAACTCCCGAAGACCCAATG 22265.5 ACKR3 AATTCAAAAACACTATTGGTGTACCTTATAACTCGA 2045 chr2 ENST000002 GTTATAAGGTACACCAATAGTG 72928.3 ACKR3 AATTCAAAAAGGCATAGTGCTGACATATATTCTCGA 2046 chr2 ENST000002 GAATATATGTCAGCACTATGCC 72928.3 ACKR3 AATTCAAAAAGCCGTTCCCTTCTCCATTATCCTCGA 2047 chr2 ENST000002 GGATAATGGAGAAGGGAACGGC 72928.3 ACVR1 AATTCAAAAATGATAATTCCCTCGACAAATTCTCGA 2048 chr2 ENST000002 GAATTTGTCGAGGGAATTATCA 63640.7 ACVR1 AATTCAAAAAGCAGAACGTATTTAGCCATTACTCGA 2049 chr2 ENST000002 GTAATGGCTAAATACGTTCTGC 63640.7 ACVR1 AATTCAAAAACTGGTCTGTCTTTGGATAATACTCGA 2050 chr2 ENST000002 GTATTATCCAAAGACAGACCAG 63640.7 ACVR2B AATTCAAAAAATGTCACGAGGCCTCTCATACCTCGA 2051 chr3 ENST000003 GGTATGAGAGGCCTCGTGACAT 52511.4 ACVR2B AATTCAAAAACCCAGCTCATGAATGACTTTGCTCGA 2052 chr3 ENST000003 GCAAAGTCATTCATGAGCTGGG 52511.4 ACVR2B AATTCAAAAACTTTGGCTTGGCTGTTCGATTCTCGA 2053 chr3 ENST000003 GAATCGAACAGCCAAGCCAAAG 52511.4 ACVRL1 AATTCAAAAACCGGGAGACTGAGATCTATAACTCG 2054 chr12 ENST000003 AGTTATAGATCTCAGTCTCCCGG 88922.8 ACVRL1 AATTCAAAAACAGGAGCACCTGATTCCTTTCCTCGA 2055 chr12 ENST000003 GGAAAGGAATCAGGTGCTCCTG 88922.8 ACVRL1 AATTCAAAAACGTGGAGATCTTCGGTACACACTCGA 2056 chr12 ENST000003 GTGTGTACCGAAGATCTCCACG 88922.8 ADIPOQ AATTCAAAAAGTTGGAGGCCTTTAGATATTACTCGA 2057 chr3 ENST000003 GTAATATCTAAAGGCCTCCAAC 20741.6 ADIPOQ AATTCAAAAAATGCTCATATCAATCCTATAACTCGA 2058 chr3 ENST000003 GTTATAGGATTGATATGAGCAT 20741.6 ADIPOQ AATTCAAAAAACGGTTAGGAAGTTGATTATTCTCGA 2059 chr3 ENST000003 GAATAATCAACTTCCTAACCGT 20741.6 AGER AATTCAAAAACACACTGCAGTCGGAGCTAATCTCGA 2060 chr6 ENST000003 GATTAGCTCCGACTGCAGTGTG 75076.8 AGER AATTCAAAAAGAAGCCAGAAATTGTAGATTCCTCG 2061 chr6 ENST000003 AGGAATCTACAATTTCTGGCTTC 75076.8 AGER AATTCAAAAATGCTGATCCTCCCTGAGATAGCTCGA 2062 chr6 ENST000003 GCTATCTCAGGGAGGATCAGCA 75076.8 AGRN AATTCAAAAAGAGTTCTGTGTGGAAGATAAACTCG 2063 chr1 ENST000003 AGTTTATCTTCCACACAGAACTC 79370.6 AGRN AATTCAAAAAGCGCACGTATGACAGTGATTGCTCGA 2064 chr1 ENST000003 GCAATCACTGTCATACGTGCGC 79370.6 AGRN AATTCAAAAAACGACGGAGTCACCTACGAAACTCG 2065 chr1 ENST000003 AGTTTCGTAGGTGACTCCGTCGT 79370.6 AHR AATTCAAAAACGGCATAGAGACCGACTTAATCTCG 2066 chr7 ENST000002 AGATTAAGTCGGTCTCTATGCCG 42057.8 AHR AATTCAAAAAGCGGCATAGAGACCGACTTAACTCG 2067 chr7 ENST000002 AGTTAAGTCGGTCTCTATGCCGC 42057.8 AHR AATTCAAAAAATCCACAGTCAGCCATAATAACTCGA 2068 chr7 ENST000002 GTTATTATGGCTGACTGTGGAT 42057.8 AHR AATTCAAAAAACTGCTTAAAGTTGGTATTAACTCGA 2069 chr7 ENST000002 GTTAATACCAACTTTAAGCAGT 42057.8 AIMP1 AATTCAAAAACAGCCTGATCTTCACACTAATCTCGA 2070 chr4 ENST000003 GATTAGTGTGAAGATCAGGCTG 58008.7 AIMP1 AATTCAAAAAAGAAGTAGATGTCGGAGAAATCTCG 2071 chr4 ENST000003 AGATTTCTCCGACATCTACTTCT 58008.7 AIMP1 AATTCAAAAAGCCAGAGTAACCCTGACTAATCTCGA 2072 chr4 ENST000003 GATTAGTCAGGGTTACTCTGGC 58008.7 AREG AATTCAAAAACCTCTTTCCAGTGGATCATAACTCGA 2073 chr4 ENST000003 GTTATGATCCACTGGAAAGAGG 95748.7 AREG AATTCAAAAATACTCGGCTCAGGCCATTATGCTCGA 2074 chr4 ENST000003 GCATAATGGCCTGAGCCGAGTA 95748.7 AREG AATTCAAAAAATTCACGGAGAATGCAAATATCTCG 2075 chr4 ENST000003 AGATATTTGCATTCTCCGTGAAT 95748.7 BCL6 AATTCAAAAATGTGCCACAGCAATATCTATTCTCGA 2076 chr3 ENST000004 GAATAGATATTGCTGTGGCACA 06870.6 BCL6 AATTCAAAAAACTGCGTTAAAGGCTCGATTTCTCGA 2077 chr3 ENST000004 GAAATCGAGCCTTTAACGCAGT 06870.6 BCL6 AATTCAAAAACCGGCTCAATAACATCGTTAACTCGA 2078 chr3 ENST000004 GTTAACGATGTTATTGAGCCGG 06870.6 BCL6 AATTCAAAAAACAAGCCAGCCGGCTCAATAACTCG 2079 chr3 ENST000004 AGTTATTGAGCCGGCTGGCTTGT 06870.6 BMP1 AATTCAAAAAACTGACGAGGACAGCTATATTCTCGA 2080 chr8 ENST000003 GAATATAGCTGTCCTCGTCAGT 06385.9 BMP1 AATTCAAAAAGCTCGTAAGTCCTCCATCAAACTCGA 2081 chr8 ENST000003 GTTTGATGGAGGACTTACGAGC 06385.9 BMP1 AATTCAAAAAACAGCTGTGCCTACGACTATCCTCGA 2082 chr8 ENST000003 GGATAGTCGTAGGCACAGCTGT 06385.9 BMP10 AATTCAAAAAAGCAAGACGGTGTCGACTTTACTCGA 2083 chr2 ENST000002 GTAAAGTCGACACCGTCTTGCT 95379.1 BMP10 AATTCAAAAAGCGTCGTCACCTACAAGTTTACTCGA 2084 chr2 ENST000002 GTAAACTTGTAGGTGACGACGC 95379.1 BMP10 AATTCAAAAACATGGCTGAACTTAGGCTATACTCGA 2085 chr2 ENST000002 GTATAGCCTAAGTTCAGCCATG 95379.1 BMP15 AATTCAAAAATACTACGCGATGGTCTCAATTCTCGA 2086 chrX ENST000002 GAATTGAGACCATCGCGTAGTA 52677.3 BMP15 AATTCAAAAAGCCTTCTTGTTACTCTATTTCCTCGAG 2087 chrX ENST000002 GAAATAGAGTAACAAGAAGGC 52677.3 BMP15 AATTCAAAAAATGGAACACAGGGCCCAAATGCTCG 2088 chrX ENST000002 AGCATTTGGGCCCTGTGTTCCAT 52677.3 BMP2 AATTCAAAAAGATCATCTGAACTCCACTAATCTCGA 2089 chr20 ENST000003 GATTAGTGGAGTTCAGATGATC 78827.4 BMP2 AATTCAAAAACCGGAGATTCTTCTTTAATTTCTCGA 2090 chr20 ENST000003 GAAATTAAAGAAGAATCTCCGG 78827.4 BMP2 AATTCAAAAACAAGATGCTTTAGGAAACAATCTCG 2091 chr20 ENST000003 AGATTGTTTCCTAAAGCATCTTG 78827.4 BMP3 AATTCAAAAACTTACAGGGACACCGGAATTTCTCGA 2092 chr4 ENST000002 GAAATTCCGGTGTCCCTGTAAG 82701.2 BMP3 AATTCAAAAAGGCCAAATCTCATCGAGATATCTCGA 2093 chr4 ENST000002 GATATCTCGATGAGATTTGGCC 82701.2 BMP3 AATTCAAAAAGTGGATTGAACCTCGGAATTGCTCGA 2094 chr4 ENST000002 GCAATTCCGAGGTTCAATCCAC 82701.2 BMP4 AATTCAAAAACCCTGGTCAATTCTGTCAATTCTCGA 2095 chr14 ENST000002 GAATTGACAGAATTGACCAGGG 45451.8 BMP4 AATTCAAAAATCCTTGAGGATAGACAGATATCTCGA 2096 chr14 ENST000002 GATATCTGTCTATCCTCAAGGA 45451.8 BMP4 AATTCAAAAAAGGGCCAGCATGTCAGGATTACTCG 2097 chr14 ENST000002 AGTAATCCTGACATGCTGGCCCT 45451.8 BMP5 AATTCAAAAATGGACGCAGTATCAACGTAAACTCG 2098 chr6 ENST000003 AGTTTACGTTGATACTGCGTCCA 70830.3 BMP5 AATTCAAAAACCAGAAGGATACGCTGCATTTCTCGA 2099 chr6 ENST000003 GAAATGCAGCGTATCCTTCTGG 70830.3 BMP5 AATTCAAAAAATGCCACCAACCACGCTATAGCTCGA 2100 chr6 ENST000003 GCTATAGCGTGGTTGGTGGCAT 70830.3 BMP6 AATTCAAAAAATACAGGAATATGGTTGTAAGCTCG 2101 chr6 ENST000002 AGCTTACAACCATATTCCTGTAT 83147.6 BMP6 AATTCAAAAACGCCGACAACAGAGTCGTAATCTCG 2102 chr6 ENST000002 AGATTACGACTCTGTTGTCGGCG 83147.6 BMP6 AATTCAAAAACTGTCTATCAAAGGTAGATTTCTCGA 2103 chr6 ENST000002 GAAATCTACCTTTGATAGACAG 83147.6 BMP7 AATTCAAAAAACGTTCCGGATCAGCGTTTATCTCGA 2104 chr20 ENST000003 GATAAACGCTGATCCGGAACGT 95863.7 BMP7 AATTCAAAAAACTCGTTTCCAGAGGTAATTACTCGA 2105 chr20 ENST000003 GTAATTACCTCTGGAAACGAGT 95863.7 BMP7 AATTCAAAAAACCATCGAGAGTTCCGGTTTGCTCGA 2106 chr20 ENST000003 GCAAACCGGAACTCTCGATGGT 95863.7 BMP8A AATTCAAAAAAGGGTGCAGTTAGCATATTAGCTCGA 2107 chr1 ENST000003 GCTAATATGCTAACTGCACCCT 31593.5 BMP8A AATTCAAAAAAGCACAGAAGTCCTATCTTAGCTCGA 2108 chr1 ENST000003 GCTAAGATAGGACTTCTGTGCT 31593.5 BMP8A AATTCAAAAAAGGTACAACACTGGCCATTTCCTCGA 2109 chr1 ENST000003 GGAAATGGCCAGTGTTGTACCT 31593.5 BMP8B AATTCAAAAACCAAGGCTACTCGGCCTATTACTCGA 2110 chr1 ENST000003 GTAATAGGCCGAGTAGCCTTGG 72827.7 BMP8B AATTCAAAAAGACCCTCACAACCACGTACATCTCGA 2111 chr1 ENST000003 GATGTACGTGGTTGTGAGGGTC 72827.7 BMP8B AATTCAAAAACGTTAACATGGTGGAGCGAGACTCG 2112 chr1 ENST000003 AGTCTCGCTCCACCATGTTAACG 72827.7 BMPR2 AATTCAAAAAGAACGGCTATGTGCGTTTAAACTCGA 2113 chr2 ENST000003 GTTTAAACGCACATAGCCGTTC 74580.8 BMPR2 AATTCAAAAAGCCTATGGAGTGAAATTATTTCTCGA 2114 chr2 ENST000003 GAAATAATTTCACTCCATAGGC 74580.8 BMPR2 AATTCAAAAAATTACCACGAGGAGATCATTACTCGA 2115 chr2 ENST000003 GTAATGATCTCCTCGTGGTAAT 74580.8 C10orf99 AATTCAAAAACATCATGTGAGGCTCTGTAAACTCGA 2116 chr10 ENST000003 GTTTACAGAGCCTCACATGATG 72126.3

C10orf99 AATTCAAAAACCCAACTCAACAAACCTGAAACTCG 2117 chr10 ENST000003 AGTTTCAGGTTTGTTGAGTTGGG 72126.3 C10orf99 AATTCAAAAAGCCATCAACTTTCAGAGCTATCTCGA 2118 chr10 ENST000003 GATAGCTCTGAAAGTTGATGGC 72126.3 C1QTNF4 AATTCAAAAAACACCGAGTTCGTCAACATTGCTCGA 2119 chr11 ENST000003 GCAATGTTGACGAACTCGGTGT 02514.3 C1QTNF4 AATTCAAAAAGCGTAAGACGCTGTCGGTTAACTCGA 2120 chr11 ENST000003 GTTAACCGACAGCGTCTTACGC 02514.3 C1QTNF4 AATTCAAAAACGAGGTGCAGGCCATGATTTACTCGA 2121 chr11 ENST000003 GTAAATCATGGCCTGCACCTCG 02514.3 C5 AATTCAAAAAACGATGGAGCCTGCGTTAATACTCGA 2122 chr9 ENST000002 GTATTAACGCAGGCTCCATCGT 23642.2 C5 AATTCAAAAATCCCGACTTCTGGTCTATTACCTCGA 2123 chr9 ENST000002 GGTAATAGACCAGAAGTCGGGA 23642.2 C5 AATTCAAAAAGCCCGAGAGAACAGCTTATATCTCG 2124 chr9 ENST000002 AGATATAAGCTGTTCTCTCGGGC 23642.2 CCL1 AATTCAAAAAGCAATCCTGTGTTACAGAAATCTCGA 2125 chr17 ENST000002 GATTTCTGTAACACAGGATTGC 25842.3 CCL1 AATTCAAAAACTGCTCCAATGAGGGCTTAATCTCGA 2126 chr17 ENST000002 GATTAAGCCCTCATTGGAGCAG 25842.3 CCL1 AATTCAAAAACCTGAGGGCAATCCTGTGTTACTCGA 2127 chr17 ENST000002 GTAACACAGGATTGCCCTCAGG 25842.3 CCL11 AATTCAAAAACCAACTCCAAAGCCATAAATACTCG 2128 chr17 ENST000003 AGTATTTATGGCTTTGGAGTTGG 05869.3 CCL11 AATTCAAAAACATTCTGAGGTAACCTCATTACTCGA 2129 chr17 ENST000003 GTAATGAGGTTACCTCAGAATG 05869.3 CCL11 AATTCAAAAATCCTCCATGAATATCAGTTATCTCGA 2130 chr17 ENST000003 GATAACTGATATTCATGGAGGA 05869.3 CCL13 AATTCAAAAATGGAATACTTCTACCATAATTCTCGA 2131 chr17 ENST000002 GAATTATGGTAGAAGTATTCCA 25844.6 CCL13 AATTCAAAAATCAAGCTGGAGTACGTGAAATCTCG 2132 chr17 ENST000002 AGATTTCACGTACTCCAGCTTGA 25844.6 CCL13 AATTCAAAAAACTCAACGTCCCATCTACTTGCTCGA 2133 chr17 ENST000002 GCAAGTAGATGGGACGTTGAGT 25844.6 CCL14 AATTCAAAAACCTAGGGACCAAGACTGAATCCTCG 2134 chr17 ENST000006 AGGATTCAGTCTTGGTCCCTAGG 18404.4 CCL14 AATTCAAAAACAGCGGATTATGGATTACTATCTCGA 2135 chr17 ENST000006 GATAGTAATCCATAATCCGCTG 18404.4 CCL14 AATTCAAAAACAAGCCCGGAATTGTCTTCATCTCGA 2136 chr17 ENST000006 GATGAAGACAATTCCGGGCTTG 18404.4 CCL15 AATTCAAAAAGCTGAAGCCCTACTCAATATACTCGA 2137 chr17 ENST000006 GTATATTGAGTAGGGCTTCAGC 17897.1 CCL15 AATTCAAAAAACAGAGTTAATGATGTCAAAGCTCG 2138 chr17 ENST000006 AGCTTTGACATCATTAACTCTGT 17897.1 CCL15 AATTCAAAAAATCCCGTGTTCACTCATGAAACTCGA 2139 chr17 ENST000006 GTTTCATGAGTGAACACGGGAT 17897.1 CCL16 AATTCAAAAAAGGAGAAGTATTTCGAATATTCTCGA 2140 chr17 ENST000006 GAATATTCGAAATACTTCTCCT 11905.1 CCL16 AATTCAAAAAAGGAACTTGTCCACGGTTAAACTCGA 2141 chr17 ENST000006 GTTTAACCGTGGACAAGTTCCT 11905.1 CCL16 AATTCAAAAACTGCCTGAAGTATTATGAGAACTCGA 2142 chr17 ENST000006 GTTCTCATAATACTTCAGGCAG 11905.1 CCL17 AATTCAAAAAGAGAGTGAAGAATGCAGTTAACTCG 2143 chr16 ENST000002 AGTTAACTGCATTCTTCACTCTC 19244.8 CCL17 AATTCAAAAAGAGTACTTCAAGGGAGCCATTCTCGA 2144 chr16 ENST000002 GAATGGCTCCCTTGAAGTACTC 19244.8 CCL17 AATTCAAAAAGCAAAGCCTTGAGAGGTCTTGCTCGA 2145 chr16 ENST000002 GCAAGACCTCTCAAGGCTTTGC 19244.8 CCL18 AATTCAAAAATCTATTGTTGAGCTGCATTATCTCGA 2146 chr17 ENST000006 GATAATGCAGCTCAACAATAGA 16054.1 CCL18 AATTCAAAAACCTTCAACTCTTCGTACATTCCTCGA 2147 chr17 ENST000006 GGAATGTACGAAGAGTTGAAGG 16054.1 CCL18 AATTCAAAAAGTCTATACCTCCTGGCAGATTCTCGA 2148 chr17 ENST000006 GAATCTGCCAGGAGGTATAGAC 16054.1 CCL19 AATTCAAAAAGAGTCAAGCATTGTGAATTATCTCGA 2149 chr9 ENST000003 GATAATTCACAATGCTTGACTC 11925.6 CCL19 AATTCAAAAAGCCGCAGCAGTTAACCTATGACTCGA 2150 chr9 ENST000003 GTCATAGGTTAACTGCTGCGGC 11925.6 CCL19 AATTCAAAAACCAACTCTGAGTGGCACCAATCTCGA 2151 chr9 ENST000003 GATTGGTGCCACTCAGAGTTGG 11925.6 CCL2 AATTCAAAAACCCAGTCACCTGCTGTTATAACTCGA 2152 chr17 ENST000002 GTTATAACAGCAGGTGACTGGG 25831.4 CCL2 AATTCAAAAACCCAGTCACCTGCTGTTATAACTCGA 2153 chr17 ENST000002 GTTATAACAGCAGGTGACTGGG 25831.4 CCL2 AATTCAAAAAGCTCGCGAGCTATAGAAGAATCTCG 2154 chr17 ENST000002 AGATTCTTCTATAGCTCGCGAGC 25831.4 CCL20 AATTCAAAAAAGTTGTCTGTGTGCGCAAATCCTCGA 2155 chr2 ENST000003 GGATTTGCGCACACAGACAACT 58813.4 CCL20 AATTCAAAAAGACCGTATTCTTCATCCTAAACTCGA 2156 chr2 ENST000003 GTTTAGGATGAAGAATACGGTC 58813.4 CCL20 AATTCAAAAAAGGGTTTAGTGCTTATCTAATCTCGA 2157 chr2 ENST000003 GATTAGATAAGCACTAAACCCT 58813.4 CCL21 AATTCAAAAACACTCTTTCTCCTGCTTTAACCTCGA 2158 chr9 ENST000002 GGTTAAAGCAGGAGAAAGAGTG 59607.6 CCL21 AATTCAAAAAGAGCTATGTGCAGACCCAAAGCTCG 2159 chr9 ENST000002 AGCTTTGGGTCTGCACATAGCTC 59607.6 CCL21 AATTCAAAAACCATCCCAGCTATCCTGTTCTCTCGA 2160 chr9 ENST000002 GAGAACAGGATAGCTGGGATGG 59607.6 CCL22 AATTCAAAAACCCTACCTCCCTGCCATTATACTCGA 2161 chr16 ENST000002 GTATAATGGCAGGGAGGTAGGG 19235.4 CCL22 AATTCAAAAAGCGTGGTGAAACACTTCTACTCTCGA 2162 chr16 ENST000002 GAGTAGAAGTGTTTCACCACGC 19235.4 CCL22 AATTCAAAAAATGTTGCTGACACCCAGAAAGCTCG 2163 chr16 ENST000002 AGCTTTCTGGGTGTCAGCAACAT 19235.4 CCL23 AATTCAAAAACACTCCTGGAGAGTTACTTTGCTCGA 2164 chr17 ENST000006 GCAAAGTAACTCTCCAGGAGTG 15050.1 CCL23 AATTCAAAAACCTTTCTCATGCTGCAGGATTCTCGA 2165 chr17 ENST000006 GAATCCTGCAGCATGAGAAAGG 15050.1 CCL23 AATTCAAAAAGAAGCTGGACACACGGATCAACTCG 2166 chr17 ENST000006 AGTTGATCCGTGTGTCCAGCTTC 15050.1 CCL24 AATTCAAAAAAGTGATCTTCACCACCAAGAACTCGA 2167 chr7 ENST000002 GTTCTTGGTGGTGAAGATCACT 22902.6 CCL24 AATTCAAAAAGTTCTTTGTTTCCAAGAGAATCTCGA 2168 chr7 ENST000002 GATTCTCTTGGAAACAAAGAAC 22902.6 CCL24 AATTCAAAAACCTGCTGCATGTTCTTTGTTTCTCGAG 2169 chr7 ENST000002 AAACAAAGAACATGCAGCAGG 22902.6 CCL25 AATTCAAAAAGCCGGATCTTTCTCCGATAAACTCGA 2170 chr19 ENST000003 GTTTATCGGAGAAAGATCCGGC 90669.7 CCL25 AATTCAAAAAGCTCCTGGATGCTCGAAATAACTCGA 2171 chr19 ENST000003 GTTATTTCGAGCATCCAGGAGC 90669.7 CCL25 AATTCAAAAACCCTCCTGATATCAGCTAATTCTCGA 2172 chr19 ENST000003 GAATTAGCTGATATCAGGAGGG 90669.7 CCL26 AATTCAAAAACACACGTGGGAGTGACATATCCTCG 2173 chr7 ENST000000 AGGATATGTCACTCCCACGTGTG 05180.8 CCL26 AATTCAAAAATCCGAAACAATTGTGACTCAGCTCGA 2174 chr7 ENST000000 GCTGAGTCACAATTGTTTCGGA 05180.8 CCL26 AATTCAAAAAGCTGTGATATTCACTACCAAACTCGA 2175 chr7 ENST000000 GTTTGGTAGTGAATATCACAGC 05180.8 CCL27 AATTCAAAAATTCGTGCTTCACCTGGCTCAACTCGA 2176 chr9 ENST000002 GTTGAGCCAGGTGAAGCACGAA 59631.4 CCL27 AATTCAAAAACCGAAAGCCACTCTCAGACAACTCG 2177 chr9 ENST000002 AGTTGTCTGAGAGTGGCTTTCGG 59631.4 CCL27 AATTCAAAAACAAGCTACTGAGGAAGGTCATCTCG 2178 chr9 ENST000002 AGATGACCTTCCTCAGTAGCTTG 59631.4 CCL28 AATTCAAAAACGGAGGTTTCACATCATATTTCTCGA 2179 chr5 ENST000003 GAAATATGATGTGAAACCTCCG 61115.4 CCL28 AATTCAAAAACACGAAACATACGGCCATAAACTCG 2180 chr5 ENST000003 AGTTTATGGCCGTATGTTTCGTG 61115.4 CCL28 AATTCAAAAATTAGAGAGTCTACAGATAAATCTCGA 2181 chr5 ENST000003 GATTTATCTGTAGACTCTCTAA 61115.4 CCL3 AATTCAAAAACCGGCAGATTCCACAGAATTTCTCGA 2182 chr17 ENST000006 GAAATTCTGTGGAATCTGCCGG 13922.1 CCL3 AATTCAAAAATTCGATTTCACAGTGTGTTTGCTCGA 2183 chr17 ENST000006 GCAAACACACTGTGAAATCGAA 13922.1 CCL3 AATTCAAAAACAACCAGTTCTCTGCATCACTCTCGA 2184 chr17 ENST000006 GAGTGATGCAGAGAACTGGTTG 13922.1 CCL4 AATTCAAAAAATGTGCCGTGTTATTGTATTACTCGA 2185 chr17 ENST000006 GTAATACAATAACACGGCACAT 15863.1 CCL4 AATTCAAAAATCCTGTCCCTTCTCTTAATTTCTCGAG 2186 chr17 ENST000006 AAATTAAGAGAAGGGACAGGA 15863.1 CCL4 AATTCAAAAACTGTGCTGATCCCAGTGAATCCTCGA 2187 chr17 ENST000006 GGATTCACTGGGATCAGCACAG 15863.1 CCL5 AATTCAAAAATGAACCTGAACTTACACAAATCTCGA 2188 chr17 ENST000006 GATTTGTGTAAGTTCAGGTTCA 03197.5 CCL5 AATTCAAAAACCTGCTGCTTTGCCTACATTGCTCGA 2189 chr17 ENST000006 GCAATGTAGGCAAAGCAGCAGG 03197.5 CCL5 AATTCAAAAACTACCACACAGCAGCAGTTACCTCGA 2190 chr17 ENST000006 GGTAACTGCTGCTGTGTGGTAG 03197.5 CCL7 AATTCAAAAACATAAAGCCTTGGATGTATATCTCGA 2191 chr17 ENST000003 GATATACATCCAAGGCTTTATG 78569.2 CCL7 AATTCAAAAAGCTGCTACAGATTTATCAATACTCGA 2192 chr17 ENST000003 GTATTGATAAATCTGTAGCAGC 78569.2 CCL7 AATTCAAAAATCTAAGGAATATGAGCTTTATCTCGA 2193 chr17 ENST000003 GATAAAGCTCATATTCCTTAGA 78569.2 CCL8 AATTCAAAAAGCTGCTTTAACGTGATCAATACTCGA 2194 chr17 ENST000003 GTATTGATCACGTTAAAGCAGC 94620.1 CCL8 AATTCAAAAACAGGTGCAGTGTGACATTATTCTCGA 2195 chr17 ENST000003 GAATAATGTCACACTGCACCTG 94620.1 CCL8 AATTCAAAAATTGTACTGCTGTTGTTGAAATCTCGA 2196 chr17 ENST000003 GATTTCAACAACAGCAGTACAA 94620.1 CCR1 AATTCAAAAAATTCTGCTAAGACGACCAAATCTCGA 2197 chr3 ENST000002 GATTTGGTCGTCTTAGCAGAAT 96140.3 CCR1 AATTCAAAAAATCTGCTACACAGGGATTATACTCGA 2198 chr3 ENST000002 GTATAATCCCTGTGTAGCAGAT 96140.3 CCR1 AATTCAAAAACCTCTGTACTCCTTGGTATTTCTCGA 2199 chr3 ENST000002 GAAATACCAAGGAGTACAGAGG 96140.3 CCR2 AATTCAAAAAACGGTGCTCCCTGTCATAAATCTCGA 2200 chr3 ENST000004

GATTTATGACAGGGAGCACCGT 45132.2 CCR2 AATTCAAAAACTTCTGGACTCCCTATAATATCTCGA 2201 chr3 ENST000004 GATATTATAGGGAGTCCAGAAG 45132.2 CCR2 AATTCAAAAAGCTGTATCACATCGGTTATTTCTCGA 2202 chr3 ENST000004 GAAATAACCGATGTGATACAGC 45132.2 CCR3 AATTCAAAAAATACAGGAGGCTCCGAATTATCTCGA 2203 chr3 ENST000003 GATAATTCGGAGCCTCCTGTAT 57422.2 CCR3 AATTCAAAAACCCAGAGGATACAGTATATAGCTCG 2204 chr3 ENST000003 AGCTATATACTGTATCCTCTGGG 57422.2 CCR3 AATTCAAAAATAGCAGCTCTTCCTGAATTTACTCGA 2205 chr3 ENST000003 GTAAATTCAGGAAGAGCTGCTA 57422.2 CCR5 AATTCAAAAAACTCTTGACAGGGCTCTATTTCTCGA 2206 chr3 ENST000002 GAAATAGAGCCCTGTCAAGAGT 92303.4 CCR5 AATTCAAAAACGAGCGAGCAAGCTCAGTTTACTCG 2207 chr3 ENST000002 AGTAAACTGAGCTTGCTCGCTCG 92303.4 CCR5 AATTCAAAAATCCATACAGTCAGTATCAATTCTCGA 2208 chr3 ENST000002 GAATTGATACTGACTGTATGGA 92303.4 CCR6 AATTCAAAAAGGTCTATGACAGACGTCTATCCTCGA 2209 chr6 ENST000003 GGATAGACGTCTGTCATAGACC 41935.9 CCR6 AATTCAAAAACGACTCCAGTGAAGATTATTTCTCGA 2210 chr6 ENST000003 GAAATAATCTTCACTGGAGTCG 41935.9 CCR6 AATTCAAAAATCGACTCCAGTGAAGATTATTCTCGA 2211 chr6 ENST000003 GAATAATCTTCACTGGAGTCGA 41935.9 CCR7 AATTCAAAAAGATGAGGTCACGGACGATTACCTCG 2212 chr17 ENST000002 AGGTAATCGTCCGTGACCTCATC 46657.2 CCR7 AATTCAAAAAGCTGGTCGTGTTGACCTATATCTCGA 2213 chr17 ENST000002 GATATAGGTCAACACGACCAGC 46657.2 CCR7 AATTCAAAAACGTGTTGACCTATATCTATTTCTCGA 2214 Chr17 ENST000002 GAAATAGATATAGGTCAACACG 46657.2 CD109 AATTCAAAAAGCCGATCCTTACATAGATATTCTCGA 2215 Chr6 ENST000002 GAATATCTATGTAAGGATCGGC 87097.5 CD109 AATTCAAAAACCCGGAGGAAATGTGACTATTCTCGA 2216 Chr6 ENST000002 GAATAGTCACATTTCCTCCGGG 87097.5 CD109 AATTCAAAAACCGCTTATCATTTGAGACCAACTCGA 2217 Chr6 ENST000002 GTTGGTCTCAAATGATAAGCGG 87097.5 CD27 AATTCAAAAACTTACCTTATGTCAGTGAGATCTCGA 2218 chr12 ENST000002 GATCTCACTGACATAAGGTAAG 66557.3 CD27 AATTCAAAAAGCACTGTAACTCTGGTCTTCTCTCGA 2219 chr12 ENST000002 GAGAAGACCAGAGTTACAGTGC 66557.3 CD27 AATTCAAAAACCACCCACTTACCTTATGTCACTCGA 2220 chr12 ENST000002 GTGACATAAGGTAAGTGGGTGG 66557.3 CD27 AATTCAAAAAGCCAGATGTGTGAGCCAGGAACTCG 2221 chr12 ENST000002 AGTTCCTGGCTCACACATCTGGC 66557.3 CD28 AATTCAAAAACCTCCAGAATTTGTATGTTAACTCGA 2222 ch2 ENST000004 GTTAACATACAAATTCTGGAGG 58610.6 CD28 AATTCAAAAACAACCTTAGCTGCAAGTATTCCTCGA 2223 ch2 ENST000004 GGAATACTTGCAGCTAAGGTTG 58610.6 CD28 AATTCAAAAATGGAGTCCTGGCTTGCTATAGCTCGA 2224 ch2 ENST000004 GCTATAGCAAGCCAGGACTCCA 58610.6 CD28 AATTCAAAAACCTCCTCCTTACCTAGACAATCTCGA 2225 ch2 ENST000004 GATTGTCTAGGTAAGGAGGAGG 58610.6 CD36 AATTCAAAAAAGAACCTATTGATGGATTAAACTCGA 2226 chr7 ENST000003 GTTTAATCCATCAATAGGTTCT 09881.11 CD36 AATTCAAAAAGCCATAATCGACACATATAAACTCG 2227 chr7 ENST000003 AGTTTATATGTGTCGATTATGGC 09881.11 CD36 AATTCAAAAAACGGCTGCAGGTCAACCTATTCTCGA 2228 chr7 ENST000003 GAATAGGTTGACCTGCAGCCGT 09881.11 CD4 AATTCAAAAACCTGATCATCAAGAATCTTAACTCGA 2229 chr12 ENST000000 GTTAAGATTCTTGATGATCAGG 11653.8 CD4 AATTCAAAAAAGAGCGGATGTCTCAGATCAACTCG 2230 chr12 ENST000000 AGTTGATCTGAGACATCCGCTCT 11653.8 CD4 AATTCAAAAACCACTCGCCTTTACAGTTGAACTCGA 2231 chr12 ENST000000 GTTCAACTGTAAAGGCGAGTGG 11653.8 CD40LG AATTCAAAAAGGGAAACAGCTGACCGTTAAACTCG 2232 chrX ENST000003 AGTTTAACGGTCAGCTGTTTCCC 70629.6 CD40LG AATTCAAAAATTCGAGTCAAGCTCCATTTATCTCGA 2233 chrX ENST000003 GATAAATGGAGCTTGACTCGAA 70629.6 CD40LG AATTCAAAAATGACGCTGGGAGTCTTCATAACTCGA 2234 chrX ENST000003 GTTATGAAGACTCCCAGCGTCA 70629.6 CD70 AATTCAAAAACCATCGTGATGGCATCTACATCTCGA 2235 chr19 ENST000002 GATGTAGATGCCATCACGATGG 45903.3 CD70 AATTCAAAAACAGCTACGTATCCATCGTGATCTCGA 2236 chr19 ENST000002 GATCACGATGGATACGTAGCTG 45903.3 CD70 AATTCAAAAACCAACCTCACTGGGACACTTTCTCGA 2237 chr19 ENST000002 GAAAGTGTCCCAGTGAGGTTGG 45903.3 CD74 AATTCAAAAACAAGTCGGAACAGCAGATAACCTCG 2238 chr5 ENST000000 AGGTTATCTGCTGTTCCGACTTG 09530.11 CD74 AATTCAAAAAGAGAACCTGAGACACCTTAAGCTCG 2239 chr5 ENST000000 AGCTTAAGGTGTCTCAGGTTCTC 09530.11 CD74 AATTCAAAAACCACACAGCTACAGCTTTCTTCTCGA 2240 chr5 ENST000000 GAAGAAAGCTGTAGCTGTGTGG 09530.11 CD8A AATTCAAAAAGCTGGACTTCGCCTGTGATATCTCGA 2241 ch2 ENST000004 GATATCACAGGCGAAGTCCAGC 09511.6 CD8A AATTCAAAAAGTGTATTCATTCTCATGATTACTCGA 2242 ch2 ENST000004 GTAATCATGAGAATGAATACAC 09511.6 CD8A AATTCAAAAACCAGAGACAGCTTGATCAAAGCTCG 2243 ch2 ENST000004 AGCTTTGATCAAGCTGTCTCTGG 09511.6 CD8A AATTCAAAAACCTTCTCCTGTCACTGGTTATCTCGA 2244 ch2 ENST000004 GATAACCAGTGACAGGAGAAGG 09511.6 CER1 AATTCAAAAAGAGAAGATGCTGTCCAGATTTCTCGA 2245 chr9 ENST000003 GAAATCTGGACAGCATCTTCTC 80911.3 CER1 AATTCAAAAACCAGCCGATAGATGGAATGAACTCG 2246 chr9 ENST000003 AGTTCATTCCATCTATCGGCTGG 80911.3 CER1 AATTCAAAAACAAGAAATTCTGGCACCACTTCTCGA 2247 chr9 ENST000003 GAAGTGGTGCCAGAATTTCTTG 80911.3 CHRD AATTCAAAAAACGTCCTGCAAAGTGTCCTTTCTCGA 2248 chr3 ENST000002 GAAAGGACACTTTGCAGGACGT 04604.5 CHRD AATTCAAAAAACTGATCCAGAGCTGGAGAAACTCG 2249 chr3 ENST000002 AGTTTCTCCAGCTCTGGATCAGT 04604.5 CHRD AATTCAAAAACGGCTGCTGAAGGGATTCTATCTCGA 2250 chr3 ENST000002 GATAGAATCCCTTCAGCAGCCG 04604.5 CKLF AATTCAAAAACCTTTGCTTGTGTTTGCACTTCTCGAG 2251 chr16 ENST000002 AAGTGCAAACACAAGCAAAGG 64001.8 CKLF AATTCAAAAACCCTGAACCATATATTGTTATCTCGA 2252 chr16 ENST000002 GATAACAATATATGGTTCAGGG 64001.8 CKLF AATTCAAAAATGGATTTGAAGTCACCGTTATCTCGA 2253 chr16 ENST000002 GATAACGGTGACTTCAAATCCA 64001.8 CLCF1 AATTCAAAAAGAAACAAACATGGTGGCAATTCTCG 2254 chr11 ENST000003 AGAATTGCCACCATGTTTGTTTC 12438.7 CLCF1 AATTCAAAAACCACAGGATTTCCTGAAAGTTCTCGA 2255 chr11 ENST000003 GAACTTTCAGGAAATCCTGTGG 12438.7 CLCF1 AATTCAAAAACATGGTGGCAATTCTACACAACTCGA 2256 chr11 ENST000003 GTTGTGTAGAATTGCCACCATG 12438.7 CMTM1 AATTCAAAAACACCACTTGCTGACCTATTTACTCGA 2257 chr16 ENST000003 GTAAATAGGTCAGCAAGTGGTG 79500.6 CMTM1 AATTCAAAAAGACCTATTTACATTGGCCCTTCTCGA 2258 chr16 ENST000003 GAAGGGCCAATGTAAATAGGTC 79500.6 CMTM1 AATTCAAAAAGCTGTGTTCCTTTCAGTAGTTCTCGA 2259 chr16 ENST000003 GAACTACTGAAAGGAACACAGC 79500.6 CMTM2 AATTCAAAAAGTAAGGAGCCATCGGACAAACCTCG 2260 chr16 ENST000002 AGGTTTGTCCGATGGCTCCTTAC 68595.2 CMTM2 AATTCAAAAACTTACTTGCTGTGATCCTTATCTCGA 2261 chr16 ENST000002 GATAAGGATCACAGCAAGTAAG 68595.2 CMTM2 AATTCAAAAACATAAGGAGCCATCGGACAAACTCG 2262 chr16 ENST000002 AGTTTGTCCGATGGCTCCTTATG 68595.2 CMTM3 AATTCAAAAACATCGTGTTTGCAACTGATTTCTCGA 2263 chr16 ENST000003 GAAATCAGTTGCAAACACGATG 61909.8 CMTM3 AATTCAAAAAGCTTCTTAACAGATGGCATTTCTCGA 2264 chr16 ENST000003 GAAATGCCATCTGTTAAGAAGC 61909.8 CMTM3 AATTCAAAAAGCTTCTTAACAGATGGCATTTCTCGA 2265 chr16 ENST000003 GAAATGCCATCTGTTAAGAAGC 61909.8 CMTM4 AATTCAAAAACAACTGGAATCTGACAGATTTCTCGA 2266 chr16 ENST000003 GAAATCTGTCAGATTCCAGTTG 94106.6 CMTM4 AATTCAAAAAGACTGGCGTCTTGCTGATTATCTCGA 2267 chr16 ENST000003 GATAATCAGCAAGACGCCAGTC 94106.6 CMTM4 AATTCAAAAAGCAGAAATTGCTGCCGTGATACTCGA 2268 chr16 ENST000003 GTATCACGGCAGCAATTTCTGC 94106.6 CMTM5 AATTCAAAAACAAGATCTACCGGACTGAGATCTCG 2269 chr14 ENST000003 AGATCTCAGTCCGGTAGATCTTG 59320.7 CMTM5 AATTCAAAAACCTGACCCTCATCATCTTCATCTCGA 2270 chr14 ENST000003 GATGAAGATGATGAGGGTCAGG 59320.7 CMTM5 AATTCAAAAACTTCCTCTATGCCACCCAGTACTCGA 2271 chr14 ENST000003 GTACTGGGTGGCATAGAGGAAG 59320.7 CMTM6 AATTCAAAAAGCCCTCACTGAGCCACTTAATCTCGA 2272 chr3 ENST000002 GATTAAGTGGCTCAGTGAGGGC 05636.3 CMTM6 AATTCAAAAACCCAAGACAGTGAAAGTAATTCTCG 2273 chr3 ENST000002 AGAATTACTTTCACTGTCTTGGG 05636.3 CMTM6 AATTCAAAAACCCAAGACAGTGAAAGTAATTCTCG 2274 chr3 ENST000002 AGAATTACTTTCACTGTCTTGGG 05636.3 CMTM7 AATTCAAAAACTGCTGAAAGTGGCGCAAATGCTCG 2275 chr3 ENST000003 AGCATTTGCGCCACTTTCAGCAG 34983.9 CMTM7 AATTCAAAAACAAAGCCCTGTCCTAATTTATCTCGA 2276 chr3 ENST000003 GATAAATTAGGACAGGGCTTTG 34983.9 CMTM7 AATTCAAAAACCTGTCGATCTTTGGTTTCATCTCGA 2277 chr3 ENST000003 GATGAAACCAAAGATCGACAGG 34983.9 CMTM8 AATTCAAAAATGCTGGTATGGACGCTTATTGCTCGA 2278 chr3 ENST000003 GCAATAAGCGTCCATACCAGCA 07526.3 CMTM8 AATTCAAAAAGCAAAGTGTTGTAGCTTATAACTCGA 2279 chr3 ENST000003 GTTATAAGCTACAACACTTTGC 07526.3 CMTM8 AATTCAAAAAATATTCCCAGAGAATTGTATTCTCGA 2280 chr3 ENST000003 GAATACAATTCTCTGGGAATAT 07526.3 CNTF AATTCAAAAAGTAACCTCTACAGGCATTTAACTCGA 2281 chr11 ENST000003 GTTAAATGCCTGTAGAGGTTAC 61987.5 CNTF AATTCAAAAAGTTGAAGGACTACAGGTATTTCTCGA 2282 chr11 ENST000003 GAAATACCTGTAGTCCTTCAAC 61987.5 CNTF AATTCAAAAAGGTGACTTCCATCAAGCTATACTCGA 2283 chr11 ENST000003 GTATAGCTTGATGGAAGTCACC 61987.5

CNTFR AATTCAAAAACATTCTCTTCAGACACAATTTCTCGA 2284 chr9 ENST000003 GAAATTGTGTCTGAAGAGAATG 51266.8 CNTFR AATTCAAAAAGCATTCTCTTCAGACACAATTCTCGA 2285 chr9 ENST000003 GAATTGTGTCTGAAGAGAATGC 51266.8 CNTFR AATTCAAAAAGCCGGGAAGGAGTACATTATCCTCG 2286 chr9 ENST000003 AGGATAATGTACTCCTTCCCGGC 51266.8 COPS5 AATTCAAAAACTAAGGATCACCATTACTTTACTCGA 2287 chr8 ENST000003 GTAAAGTAATGGTGATCCTTAG 57849.8 COPS5 AATTCAAAAACCAGACTATTCCACTTAATAACTCGA 2288 chr8 ENST000003 GTTATTAAGTGGAATAGTCTGG 57849.8 COPS5 AATTCAAAAACAGTCTCTGAGAAGTACTTTACTCGA 2289 chr8 ENST000003 GTAAAGTACTTCTCAGAGACTG 57849.8 CRLF1 AATTCAAAAACGATGTACTCACGCTGGATATCTCGA 2290 chr19 ENST000003 GATATCCAGCGTGAGTACATCG 92386.7 CRLF1 AATTCAAAAACGATGTACTCACGCTGGATATCTCGA 2291 chr19 ENST000003 GATATCCAGCGTGAGTACATCG 92386.7 CRLF1 AATTCAAAAACCCAGAGAAACCCGTCAACATCTCG 2292 chr19 ENST000003 AGATGTTGACGGGTTTCTCTGGG 92386.7 CSF1 AATTCAAAAATCTCCTGGTACAAGACATAATCTCGA 2293 chr1 ENST000003 GATTATGTCTTGTACCAGGAGA 29608.10 CSF1 AATTCAAAAAGTCGGCCTGATTTCCCGTAAACTCGA 2294 chr1 ENST000003 GTTTACGGGAAATCAGGCCGAC 29608.10 CSF1 AATTCAAAAATTGACAAGGACTGGAATATTTCTCGA 2295 chr1 ENST000003 GAAATATTCCAGTCCTTGTCAA 29608.10 CSF AATTCAAAAAGTGAACAGCAAGTTCTATAAACTCG 2296 chr5 ENST000002 AGTTTATAGAACTTGCTGTTCAC 86301.7 CSF1R AATTCAAAAAACAGGAGAGAGCGGGACTATACTCG 2297 chr5 ENST000002 AGTATAGTCCCGCTCTCTCCTGT 86301.7 CSF1R AATTCAAAAAGCTGCTATTGTACAAGTATAACTCGA 2298 Chr5 ENST000002 GTTATACTTGTACAATAGCAGC 86301.7 CSF2 AATTCAAAAAGGAGCTGCTCTCTCATGAAACCTCGA 2299 chr5 ENST000002 GGTTTCATGAGAGAGCAGCTCC 96871.3 CSF2 AATTCAAAAACCCAGATTATCACCTTTGAAACTCGA 2300 chr5 ENST000002 GTTTCAAAGGTGATAATCTGGG 96871.3 CSF2 AATTCAAAAAGAAGTCATCTCAGAAATGTTTCTCGA 2301 chr5 ENST000002 GAAACATTTCTGAGATGACTTC 96871.3 CSF3 AATTCAAAAAGTCTATTTAAGCCTCATATTTCTCGA 2302 chr17 ENST000002 GAAATATGAGGCTTAAATAGAC 25474.6 CSF3 AATTCAAAAAGATAGGTAAATACCAAGTATTCTCGA 2303 chr17 ENST000002 GAATACTTGGTATTTACCTATC 25474.6 CSF3 AATTCAAAAAGCTTAGAGCAAGTGAGGAAGACTCG 2304 chr17 ENST000002 AGTCTTCCTCACTTGCTCTAAGC 25474.6 CSF3R AATTCAAAAACAGCCAGGCCTGCACATAAATCTCG 2305 chr1 ENST000003 AGATTTATGTGCAGGCCTGGCTG 61632.8 CSF3R AATTCAAAAACTATGCCTACTCTCAAGAAATCTCGA 2306 chr1 ENST000003 GATTTCTTGAGAGTAGGCATAG 61632.8 CSF3R AATTCAAAAACCAGCTTCACTCTGAAGAGTTCTCGA 2307 chr1 ENST000003 GAACTCTTCAGAGTGAAGCTGG 61632.8 CTF1 AATTCAAAAAGAGCAGCTGCTCCAGGAATATCTCG 2308 chr16 ENST000002 AGATATTCCTGGAGCAGCTGCTC 79804.2 CTF1 AATTCAAAAAGTCTCTCCTTCCGCTTCTTTGCTCGAG 2309 chr16 ENST000002 CAAAGAAGCGGAAGGAGAGAC 79804.2 CTF1 AATTCAAAAATGTCTGTCTGTCTGCTCTTAGCTCGA 2310 chr16 ENST000002 GCTAAGAGCAGACAGACAGACA 79804.2 CX3CL1 AATTCAAAAACCCGGAGCTGTGGTAGTAATTCTCGA 2311 chr16 ENST000000 GAATTACTACCACAGCTCCGGG 06053.6 CX3CL1 AATTCAAAAAGCTGCTGCCCTAACTCGAAATCTCGA 2312 chr16 ENST000000 GATTTCGAGTTAGGGCAGCAGC 06053.6 CX3CL1 AATTCAAAAACGGTGTGACGAAATGCAACATCTCG 2313 chr16 ENST000000 AGATGTTGCATTTCGTCACACCG 06053.6 CX3CR1 AATTCAAAAATGGCCTGTGTCTAGTTGTTTGCTCGA 2314 chr3 ENST000003 GCAAACAACTAGACACAGGCCA 99220.2 CX3CR1 AATTCAAAAATGGGATCCCTCATCCTCATACCTCGA 2315 chr3 ENST000003 GGTATGAGGATGAGGGATCCCA 99220.2 CX3CR1 AATTCAAAAAGCTTTGCTCATCCACTATCAACTCGA 2316 chr3 ENST000003 GTTGATAGTGGATGAGCAAAGC 99220.2 CXCL1 AATTCAAAAAACCTGCACACTGTCCTATTATCTCGA 2317 chr4 ENST000003 GATAATAGGACAGTGTGCAGGT 95761.3 CXCL1 AATTCAAAAAAGATGCTGAACAGTGACAAATCTCG 2318 chr4 ENST000003 AGATTTGTCACTGTTCAGCATCT 95761.3 CXCL1 AATTCAAAAAGTTCTCCAGTCATTATGTTAACTCGA 2319 chr4 ENST000003 GTTAACATAATGACTGGAGAAC 95761.3 CXCL10 AATTCAAAAAGTATATGTCAAGCCATAATTGCTCGA 2320 chr4 ENST000003 GCAATTATGGCTTGACATATAC 06602.2 CXCL10 AATTCAAAAAACTCTACCCTGGCACTATAATCTCGA 2321 chr4 ENST000003 GATTATAGTGCCAGGGTAGAGT 06602.2 CXCL10 AATTCAAAAACCTGTTAATCCAAGGTCTTTACTCGA 2322 chr4 ENST000003 GTAAAGACCTTGGATTAACAGG 06602.2 CXCL11 AATTCAAAAAGCTGGTTACCATCGGAGTTTACTCGA 2323 chr4 ENST000003 GTAAACTCCGATGGTAACCAGC 06621.7 CXCL11 AATTCAAAAAGCAGTGAAAGTGGCAGATATTCTCG 2324 chr4 ENST000003 AGAATATCTGCCACTTTCACTGC 06621.7 CXCL11 AATTCAAAAAGAAGCAAGCAAGGCTTATAATCTCG 2325 chr4 ENST000003 AGATTATAAGCCTTGCTTGCTTC 06621.7 CXCL12 AATTCAAAAAGCTTAGACTAAGGCCATTATTCTCGA 2326 chr10 ENST000003 GAATAATGGCCTTAGTCTAAGC 43575.10 CXCL12 AATTCAAAAACTCTCACTATACCAGTATAATCTCGA 2327 chr10 ENST000003 GATTATACTGGTATAGTGAGAG 43575.10 CXCL12 AATTCAAAAACAAACTGTGCCCTTCAGATTGCTCGA 2328 chr10 ENST000003 GCAATCTGAAGGGCACAGTTTG 43575.10 CXCL13 AATTCAAAAAGATTCCCTGATGCTGATATTTCTCGA 2329 chr4 ENST000002 GAAATATCAGCATCAGGGAATC 86758.4 CXCL13 AATTCAAAAAAGGAATCCATGTAGTAGATATCTCGA 2330 chr4 ENST000002 GATATCTACTACATGGATTCCT 86758.4 CXCL13 AATTCAAAAAAGGTGTTCTGGAGGTCTATTACTCGA 2331 chr4 ENST000002 GTAATAGACCTCCAGAACACCT 86758.4 CXCL14 AATTCAAAAAATTTGTCCATACGTCACTATACTCGA 2332 chr5 ENST000003 GTATAGTGACGTATGGACAAAT 37225.5 CXCL14 AATTCAAAAACAAAGGACTTTGCAGATTAAACTCG 2333 chr5 ENST000003 AGTTTAATCTGCAAAGTCCTTTG 37225.5 CXCL14 AATTCAAAAAGCGCAGGGTCTACGAAGAATACTCG 2334 chr5 ENST000003 AGTATTCTTCGTAGACCCTGCGC 37225.5 CXCL16 AATTCAAAAAACATCCAGCCTACACGTATTTCTCGA 2335 chr17 ENST000002 GAAATACGTGTAGGCTGGATGT 93778.10 CXCL16 AATTCAAAAATCTGAAGGTGCGAGGATTATACTCGA 2336 chr17 ENST000002 GTATAATCCTCGCACCTTCAGA 93778.10 CXCL16 AATTCAAAAATCCAGATCTGCCGGTTCATTACTCGA 2337 chr17 ENST000002 GTAATGAACCGGCAGATCTGGA 93778.10 CXCL17 AATTCAAAAAGCGCCCACTCTTCCAATTAAACTCGA 2338 chr19 ENST000006 GTTTAATTGGAAGAGTGGGCGC 01181.5 CXCL17 AATTCAAAAATCCAGAGCCTGCCAGCAATTTCTCGA 2339 chr19 ENST000006 GAAATTGCTGGCAGGCTCTGGA 01181.5 CXCL17 AATTCAAAAAAGAATGTGAGTGCAAAGATTGCTCG 2340 chr19 ENST000006 AGCAATCTTTGCACTCACATTCT 01181.5 CXCL2 AATTCAAAAACTTGCACACTCTCCCATTATACTCGA 2341 chr4 ENST000005 GTATAATGGGAGAGTGTGCAAG 08487.2 CXCL2 AATTCAAAAAGCAGATATTCTCTAGTCATTTCTCGA 2342 chr4 ENST000005 GAAATGACTAGAGAATATCTGC 08487.2 CXCL2 AATTCAAAAAATTTCTTCGTGATGACATATCCTCGA 2343 chr4 ENST000005 GGATATGTCATCACGAAGAAAT 08487.2 CXCL3 AATTCAAAAATTACGAGGGTTCTACTTATTTCTCGA 2344 chr4 ENST000002 GAAATAAGTAGAACCCTCGTAA 96026.4 CXCL3 AATTCAAAAAATTTAGTGGGAGACCATAATGCTCGA 2345 chr4 ENST000002 GCATTATGGTCTCCCACTAAAT 96026.4 CXCL3 AATTCAAAAAACTGACAGGAGAGAAGTAAGACTCG 2346 chr4 ENST000002 AGTCTTACTTCTCTCCTGTCAGT 96026.4 CXCL5 AATTCAAAAATGAATTGTAGGTGACTATTATCTCGA 2347 chr4 ENST000002 GATAATAGTCACCTACAATTCA 96027.4 CXCL5 AATTCAAAAACAGACCACGCAAGGAGTTCATCTCG 2348 chr4 ENST000002 AGATGAACTCCTTGCGTGGTCTG 96027.4 CXCL5 AATTCAAAAACGGGAAGGAAATTTGTCTTGACTCGA 2349 chr4 ENST000002 GTCAAGACAAATTTCCTTCCCG 96027.4 CXCL6 AATTCAAAAATTTACCCTAGGATGCTATTTACTCGA 2350 chr4 ENST000002 GTAAATAGCATCCTAGGGTAAA 26317.9 CXCL6 AATTCAAAAAGTTGCACTTGTTTACGCGTTACTCGA 2351 chr4 ENST000002 GTAACGCGTAAACAAGTGCAAC 26317.9 CXCL6 AATTCAAAAAGCTGTGGATTTCGTATGGAAACTCGA 2352 chr4 ENST000002 GTTTCCATACGAAATCCACAGC 26317.9 CXCL8 AATTCAAAAATGCGCCAACACAGAAATTATTCTCGA 2353 chr4 ENST000003 GAATAATTTCTGTGTTGGCGCA 07407.7 CXCL8 AATTCAAAAACAAGAGAATATCCGAACTTTACTCGA 2354 chr4 ENST000003 GTAAAGTTCGGATATTCTCTTG 07407.7 CXCL8 AATTCAAAAATGCACGGGAGAATATACAAATCTCG 2355 chr4 ENST000003 AGATTTGTATATTCTCCCGTGCA 07407.7 CXCL9 AATTCAAAAACCAAAGGAGGATGGCATATAACTCG 2356 chr4 ENST000002 AGTTATATGCCATCCTCCTTTGG 64888.5 CXCL9 AATTCAAAAACCAAACGTTAAGAATTGTTAACTCGA 2357 chr4 ENST000002 GTTAACAATTCTTAACGTTTGG 64888.5 CXCL9 AATTCAAAAAGATGTGAAGGAACTGATTAAACTCG 2358 chr4 ENST000002 AGTTTAATCAGTTCCTTCACATC 64888.5 CXCR1 AATTCAAAAACTTGGCACGTCATCGTGTTACCTCGA 2359 chr2 ENST000002 GGTAACACGATGACGTGCCAAG 95683.2 CXCR1 AATTCAAAAAACCCACTAACTGGCTAATTAGCTCGA 2360 chr2 ENST000002 GCTAATTAGCCAGTTAGTGGGT 95683.2 CXCR1 AATTCAAAAAGAGACACTCAACAAGTATGTTCTCGA 2361 chr2 ENST000002 GAACATACTTGTTGAGTGTCTC 95683.2 CXCR2 AATTCAAAAAGAAGCGCTACTTGGTCAAATTCTCGA 2362 chr2 ENST000003 GAATTTGACCAAGTAGCGCTTC 18507.6 CXCR2 AATTCAAAAAGCCACTAAATTGACACTTAAACTCGA 2363 chr2 ENST000003 GTTTAAGTGTCAATTTAGTGGC 18507.6 CXCR2 AATTCAAAAACCCTGGAAATCAACAAGTATTCTCGA 2364 chr2 ENST000003 GAATACTTGTTGATTTCCAGGG 18507.6 CXCR3 AATTCAAAAACCTTCTCATTTGGAAACTAAACTCGA 2365 chrX ENST000003 GTTTAGTTTCCAAATGAGAAGG 73693.3 CXCR3 AATTCAAAAACGCTACCTGAACATAGTTCATCTCGA 2366 chrX ENST000003 GATGAACTATGTTCAGGTAGCG 73693.3 CXCR3 AATTCAAAAAGAGTACAAGGCATGGCGTAGACTCG 2367 chrX ENST000003 AGTCTACGCCATGCCTTGTACTC 73693.3

CXCR4 AATTCAAAAACTATTCCCGACTTCATCTTTGCTCGA 2368 chr2 ENST000004 GCAAAGATGAAGTCGGGAATAG 09817.1 CXCR4 AATTCAAAAAGCGTGTAGTGAATCACGTAAACTCG 2369 chr2 ENST000004 AGTTTACGTGATTCACTACACGC 09817.1 CXCR4 AATTCAAAAACCTGTTCTTAAGACGTGATTTCTCGA 2370 chr2 ENST000004 GAAATCACGTCTTAAGAACAGG 09817.1 CXCR6 AATTCAAAAAGCTTGCTCATCTGGGTGATATCTCGA 2371 chr3 ENST000003 GATATCACCCAGATGAGCAAGC 04552.4 CXCR6 AATTCAAAAATACTGGGCATCTACACTATTACTCGA 2372 chr3 ENST000003 GTAATAGTGTAGATGCCCAGTA 04552.4 CXCR6 AATTCAAAAATTATCTATGGCAATGTCTTTACTCGA 2373 chr3 ENST000003 GTAAAGACATTGCCATAGATAA 04552.4 EBI3 AATTCAAAAATGAACTGTCACTGTGAGATATCTCGA 2374 chr19 ENST000002 GATATCTCACAGTGACAGTTCA 21847.5 EBI3 AATTCAAAAAATGTACTACTCTCTCCTTTACCTCGA 2375 chr19 ENST000002 GGTAAAGGAGAGAGTAGTACAT 21847.5 EBI3 AATTCAAAAAGCCTTTCATAACAGAGCACATCTCGA 2376 chr19 ENST000002 GATGTGCTCTGTTATGAAAGGC 21847.5 EDN1 AATTCAAAAACCATGAGAAACAGCGTCAAATCTCG 2377 chr6 ENST000003 AGATTTGACGCTGTTTCTCATGG 79375.5 EDN1 AATTCAAAAAGCTCGTCCCTGATGGATAAAGCTCGA 2378 chr6 ENST000003 GCTTTATCCATCAGGGACGAGC 79375.5 EDN1 AATTCAAAAAAGACAAGAAGTGCTGGAATTTCTCG 2379 chr6 ENST000003 AGAAATTCCAGCACTTCTTGTCT 79375.5 ELANE AATTCAAAAAGCACTGCGTGGCGAATGTAAACTCG 2380 chr19 ENST000002 AGTTTACATTCGCCACGCAGTGC 63621.1 ELANE AATTCAAAAATGCTCAACGACATCGTGATTCCTCGA 2381 chr19 ENST000002 GGAATCACGATGTCGTTGAGCA 63621.1 ELANE AATTCAAAAACAACGGGCTAATCCACGGAATCTCG 2382 chr19 ENST000002 AGATTCCGTGGATTAGCCCGTTG 63621.1 ENG AATTCAAAAAGCAGGTGTCAGCAAGTATGATCTCG 2383 chr9 ENST000003 AGATCATACTTGCTGACACCTGC 44849.4 ENG AATTCAAAAAGCAGGTGTCAGCAAGTATGATCTCG 2384 chr9 ENST000003 AGATCATACTTGCTGACACCTGC 44849.4 ENG AATTCAAAAAGTCTTGCAGAAACAGTCCATTCTCGA 2385 chr9 ENST000003 GAATGGACTGTTTCTGCAAGAC 44849.4 EPO AATTCAAAAACCCAGACACCAAAGTTAATTTCTCGA 2386 chr7 ENST000002 GAAATTAACTTTGGTGTCTGGG 52723.2 EPO AATTCAAAAATGCAGCTGCATGTGGATAAAGCTCG 2387 chr7 ENST000002 AGCTTTATCCACATGCAGCTGCA 52723.2 EPO AATTCAAAAAAGAGCAACTCTGAGATCTAAGCTCG 2388 chr7 ENST000002 AGCTTAGATCTCAGAGTTGCTCT 52723.2 FAM3B AATTCAAAAATTGGAACTCCCTTCCGAAATTCTCGA 2389 chr21 ENST000003 GAATTTCGGAAGGGAGTTCCAA 57985.6 FAM3B AATTCAAAAATAAATCCAACAGCCCATATTTCTCGA 2390 chr21 ENST000003 GAAATATGGGCTGTTGGATTTA 57985.6 FAM3B AATTCAAAAATCAGGTCTAGCTGGGTATTTACTCGA 2391 chr21 ENST000003 GTAAATACCCAGCTAGACCTGA 57985.6 FAM3C AATTCAAAAACTTGGTGTGTGCATGAGTATTCTCGA 2392 chr7 ENST000003 GAATACTCATGCACACACCAAG 59943.7 FAM3C AATTCAAAAAGAGGAGATGTGGCACCATTTACTCG 2393 chr7 ENST000003 AGTAAATGGTGCCACATCTCCTC 59943.7 FAM3C AATTCAAAAAGCCATACAAGATGGAACAATACTCG 2394 chr7 ENST000003 AGTATTGTTCCATCTTGTATGGC 59943.7 FAM3D AATTCAAAAACACCTAGTGAAATTCCTTAAACTCGA 2395 chr3 ENST000003 GTTTAAGGAATTTCACTAGGTG 58781.6 FAM3D AATTCAAAAACATGTACTCTGGAGATGTTATCTCGA 2396 chr3 ENST000003 GATAACATCTCCAGAGTACATG 58781.6 FAM3D AATTCAAAAACAATGTGGGCAGAGGCCTAAACTCG 2397 chr3 ENST000003 AGTTTAGGCCTCTGCCCACATTG 58781.6 FAS AATTCAAAAAGCGTATGACACATTGATTAAACTCGA 2398 chr10 ENST000003 GTTTAATCAATGTGTCATACGC 55740.6 FAS AATTCAAAAACCTGAAACAGTGGCAATAAATCTCG 2399 chr10 ENST000003 AGATTTATTGCCACTGTTTCAGG 55740.6 FAS AATTCAAAAACTATCATCCTCAAGGACATTACTCGA 2400 chr10 ENST000003 GTAATGTCCTTGAGGATGATAG 55740.6 FASLG AATTCAAAAAGACTAGAGGCTTGCATAATAACTCG 2401 chr1 ENST000003 AGTTATTATGCAAGCCTCTAGTC 67721.2 FASLG AATTCAAAAAACTGGGCTGTACTTTGTATATCTCGA 2402 chr1 ENST000003 GATATACAAAGTACAGCCCAGT 67721.2 FASLG AATTCAAAAATGAGCTCTCTCTGGTCAATTTCTCGA 2403 chr1 ENST000003 GAAATTGACCAGAGAGAGCTCA 67721.2 FGF2 AATTCAAAAAGAAACGAACTGGGCAGTATAACTCG 2404 chr4 ENST000006 AGTTATACTGCCCAGTTCGTTTC 08478.1 FGF2 AATTCAAAAATATAGCTCAGTTTGGATAATTCTCGA 2405 chr4 ENST000006 GAATTATCCAAACTGAGCTATA 08478.1 FGF2 AATTCAAAAATGAACGATTGGAATCTAATAACTCGA 2406 chr4 ENST000006 GTTATTAGATTCCAATCGTTCA 08478.1 FLT3LG AATTCAAAAACTGTCTGACTACCTGCTTCAACTCGA 2407 chr19 ENST000005 GTTGAAGCAGGTAGTCAGACAG 94009.5 FLT3LG AATTCAAAAATCCTCCGACTTCGCTGTCAAACTCGA 2408 chr19 ENST000005 GTTTGACAGCGAAGTCGGAGGA 94009.5 FLT3LG AATTCAAAAAGCTTCGTCCAGACCAACATCTCTCGA 2409 chr19 ENST000005 GAGATGTTGGTCTGGACGAAGC 94009.5 FOXP3 AATTCAAAAAAGCTGGAGTTCCGCAAGAAACCTCG 2410 chrX ENST000003 AGGTTTCTTGCGGAACTCCAGCT 76207.8 FOXP3 AATTCAAAAATCCTACCCACTGCTGGCAAATCTCGA 2411 chrX ENST000003 GATTTGCCAGCAGTGGGTAGGA 76207.8 FOXP3 AATTCAAAAATGTCCCTCACTCAACACAAACCTCGA 2412 chrX ENST000003 GGTTTGTGTTGAGTGAGGGACA 76207.8 FOXP3 AATTCAAAAACACACGCATGTTTGCCTTCTTCTCGA 2413 chrX ENST000003 GAAGAAGGCAAACATGCGTGTG 76207.8 FZD4 AATTCAAAAACGTGTGTGATTGCCTGTTATTCTCGA 2414 chr11 ENST000005 GAATAACAGGCAATCACACACG 31380.1 FZD4 AATTCAAAAATCTCAGTATGTGCTATAATATCTCGA 2415 chr11 ENST000005 GATATTATAGCACATACTGAGA 31380.1 FZD4 AATTCAAAAATTCTCAGTATGTGCTATAATACTCGA 2416 chr11 ENST000005 GTATTATAGCACATACTGAGAA 31380.1 GATA3 AATTCAAAAAAGCCTAAACGCGATGGATATACTCG 2417 chr10 ENST000003 AGTATATCCATCGCGTTTAGGCT 46208.4 GATA3 AATTCAAAAACCCAAGAACAGCTCGTTTAACCTCGA 2418 chr10 ENST000003 GGTTAAACGAGCTGTTCTTGGG 46208.4 GATA3 AATTCAAAAAGCCAAGAAGTTTAAGGAATATCTCG 2419 chr10 ENST000003 AGATATTCCTTAAACTTCTTGGC 46208.4 GATA3 AATTCAAAAACCCTGTAATTGTTGTTTGTATCTCGA 2420 chr10 ENST000003 GATACAAACAACAATTACAGGG 46208.4 GBP1 AATTCAAAAACCAGATGAGTACCTGACATACCTCGA 2421 chr1 ENST000003 GGTATGTCAGGTACTCATCTGG 70473.4 GBP1 AATTCAAAAACGACGAAAGGCATGTACCATACTCG 2422 chr1 ENST000003 AGTATGGTACATGCCTTTCGTCG 70473.4 GBP1 AATTCAAAAACGACGAAAGGCATGTACCATACTCG 2423 chr1 ENST000003 AGTATGGTACATGCCTTTCGTCG 70473.4 GDF1 AATTCAAAAAGTTCACCAAGCTCAACATTTACTCGA 2424 chr19 ENST000002 GTAAATGTTGAGCTTGGTGAAC 47005.7 GDF1 AATTCAAAAAGAGTTCACCAAGCTCAACATTCTCGA 2425 chr19 ENST000002 GAATGTTGAGCTTGGTGAACTC 47005.7 GDF1 AATTCAAAAACCCTTATGAACCTCTACTGGTCTCGA 2426 chr19 ENST000002 GACCAGTAGAGGTTCATAAGGG 47005.7 GDF10 AATTCAAAAACAGGATAATCGTGGTGTAAATCTCGA 2427 chr10 ENST000005 GATTTACACCACGATTATCCTG 80279.1 GDF10 AATTCAAAAACGACCAGAAGGCCGTGTATTTCTCGA 2428 chr10 ENST000005 GAAATACACGGCCTTCTGGTCG 80279.1 GDF10 AATTCAAAAACTGTCCGCCAGTGCATCATTACTCGA 2429 chr10 ENST000005 GTAATGATGCACTGGCGGACAG 80279.1 GDF11 AATTCAAAAACCTGCAGATCTTGCGACTAAACTCGA 2430 chr12 ENST000002 GTTTAGTCGCAAGATCTGCAGG 57868.9 GDF11 AATTCAAAAAGATCGCTGTGGCTGCTCTTAACTCGA 2431 chr12 ENST000002 GTTAAGAGCAGCCACAGCGATC 57868.9 GDF11 AATTCAAAAAGAGATGTAGAGACAGTGATAGCTCG 2432 chr12 ENST000002 AGCTATCACTGTCTCTACATCTC 57868.9 GDF15 AATTCAAAAAAGACTCCAGATTCCGAGAGTTCTCGA 2433 chr19 ENST000002 GAACTCTCGGAATCTGGAGTCT 52809.3 GDF15 AATTCAAAAAGCTCCAGACCTATGATGACTTCTCGA 2434 chr19 ENST000002 GAAGTCATCATAGGTCTGGAGC 52809.3 GDF15 AATTCAAAAAAGAGCTGGGAAGATTCGAACACTCG 2435 chr19 ENST000002 AGTGTTCGAATCTTCCCAGCTCT 52809.3 GDF2 AATTCAAAAACAACAGGTACACGTCCGATAACTCG 2436 chr10 ENST000005 AGTTATCGGACGTGTACCTGTTG 81492.2 GDF2 AATTCAAAAATGAAAGGAAGCGTGGTCATTTCTCGA 2437 chr10 ENST000005 GAAATGACCACGCTTCCTTTCA 81492.2 GDF2 AATTCAAAAATATGAAGCCTACGAGTGTAAGCTCG 2438 chr10 ENST000005 AGCTTACACTCGTAGGCTTCATA 81492.2 GDF3 AATTCAAAAAACCGTCACCAGCTATTCATTACTCGA 2439 chr12 ENST000003 GTAATGAATAGCTGGTGACGGT 29913.3 GDF3 AATTCAAAAACTCTCAACAGCTCCAATTATGCTCGA 2440 chr12 ENST000003 GCATAATTGGAGCTGTTGAGAG 29913.3 GDF3 AATTCAAAAATTGGGCCAGGCAGTCCAATTTCTCGA 2441 chr12 ENST000003 GAAATTGGACTGCCTGGCCCAA 29913.3 GDF5 AATTCAAAAACAACACCATCACCAGCTTTATCTCGA 2442 chr20 ENST000003 GATAAAGCTGGTGATGGTGTTG 74369.7 GDF5 AATTCAAAAAATGAGACTCAGCCCACCATTTCTCGA 2443 chr20 ENST000003 GAAATGGTGGGCTGAGTCTCAT 74369.7 GDF5 AATTCAAAAATGAGTGTGACTTGGGCTAAAGCTCGA 2444 chr20 ENST000003 GCTTTAGCCCAAGTCACACTCA 74369.7 GDF6 AATTCAAAAAGACTCCCATCAGCATTCTATACTCGA 2445 chr8 ENST000002 GTATAGAATGCTGATGGGAGTC 87020.6 GDF6 AATTCAAAAACGAGTACATGCTGTCAATCTACTCGA 2446 chr8 ENST000002 GTAGATTGACAGCATGTACTCG 87020.6 GDF6 AATTCAAAAACAGTCTTCCAAGTCGGCTAATCTCGA 2447 chr8 ENST000002 GATTAGCCGACTTGGAAGACTG 87020.6 GDF7 AATTCAAAAAGCAGAGGAAAGAGAGCTTATTCTCG 2448 chr2 ENST000002 AGAATAAGCTCTCTTTCCTCTGC 72224.4 GDF7 AATTCAAAAAGTTCGACGTGTCCAGCCTTAACTCGA 2449 Chr2 ENST000002 GTTAAGGCTGGACACGTCGAAC 72224.4 GDF7 AATTCAAAAACCACTTCATGATGTCGCTTTACTCGA 2450 Chr2 ENST000002 GTAAAGCGACATCATGAAGTGG 72224.4 GDF9 AATTCAAAAAGATGGCTCAATTGCCTATAAACTCGA 2451 Chr5 ENST000003

GTTTATAGGCAATTGAGCCATC 78673.2 GDF9 AATTCAAAAACCATCAGTGGAACTGCTATTTCTCGA 2452 Chr5 ENST000003 GAAATAGCAGTTCCACTGATGG 78673.2 GDF9 AATTCAAAAAGAGTGAATACTTCAGACAATTCTCGA 2453 Chr5 ENST000003 GAATTGTCTGAAGTATTCACTC 78673.2 GPI AATTCAAAAACGTCTGGTATGTCTCCAACATCTCGA 2454 chr19 ENST000003 GATGTTGGAGACATACCAGACG 56487.9 GPI AATTCAAAAACGTCTGGTATGTCTCCAACATCTCGA 2455 chr19 ENST000003 GATGTTGGAGACATACCAGACG 56487.9 GPI AATTCAAAAAGCGGATGTTCAATGGTGAGAACTCG 2456 chr19 ENST000003 AGTTCTCACCATTGAACATCCGC 56487.9 GREM1 AATTCAAAAAGCAGTGTCGTTGCATATCCATCTCGA 2457 chr15 ENST000006 GATGGATATGCAACGACACTGC 22074.1 GREM1 AATTCAAAAAACAGCCACCTACCAAGAAGAACTCG 2458 chr15 ENST000006 AGTTCTTCTTGGTAGGTGGCTGT 22074.1 GREM1 AATTCAAAAACAACAGTCGCACCATCATCAACTCGA 2459 chr15 ENST000006 GTTGATGATGGTGCGACTGTTG 22074.1 GREM2 AATTCAAAAAGCTGTGAAGGAAGGAAATTTACTCG 2460 chr1 ENST000003 AGTAAATTTCCTTCCTTCACAGC 18160.4 GREM2 AATTCAAAAACAAGGTGCATTTCTGTCATTTCTCGA 2461 chr1 ENST000003 GAAATGACAGAAATGCACCTTG 18160.4 GREM2 AATTCAAAAACGGAAGTAGACGTAACTTATTCTCGA 2462 chr1 ENST000003 GAATAAGTTACGTCTACTTCCG 18160.4 GRN AATTCAAAAAGCCCTGATAGTCAGTTCGAATCTCGA 2463 chr17 ENST000000 GATTCGAACTGACTATCAGGGC 53867.7 GRN AATTCAAAAAGCCCTGATAGTCAGTTCGAATCTCGA 2464 chr17 ENST000000 GATTCGAACTGACTATCAGGGC 53867.7 GRN AATTCAAAAACTTCCAAAGATCAGGTAACAACTCG 2465 chr17 ENST000000 AGTTGTTACCTGATCTTTGGAAG 53867.7 HAX1 AATTCAAAAAACAGACACTTCGGGACTCAATCTCGA 2466 chr1 ENST000003 GATTGAGTCCCGAAGTGTCTGT 28703.11 HAX1 AATTCAAAAACCAGCCCAAATCCTATTTCAACTCGA 2467 chr1 ENST000003 GTTGAAATAGGATTTGGGCTGG 28703.11 HAX1 AATTCAAAAACCAGAGGCCATTTCATAGGTTCTCGA 2468 chr1 ENST000003 GAACCTATGAAATGGCCTCTGG 28703.11 HFE2 AATTCAAAAAGACATGATCATTAGCCATAAGCTCGA 2469 chr1 ENST000003 GCTTATGGCTAATGATCATGTC 36751.10 HFE2 AATTCAAAAAGCCTACATTGGCACAACTATACTCGA 2470 chr1 ENST000003 GTATAGTTGTGCCAATGTAGGC 36751.10 HFE2 AATTCAAAAAGAAGCTCACCATCATATTTAACTCGA 2471 chr1 ENST000003 GTTAAATATGATGGTGAGCTTC 36751.10 HMGB1 AATTCAAAAAGATGCAGCTTATACGAAATAACTCG 2472 chr13 ENST000003 AGTTATTTCGTATAAGCTGCATC 39872.8 HMGB1 AATTCAAAAAGTTGGTGCACAGCACAAATTACTCGA 2473 chr13 ENST000003 GTAATTTGTGCTGTGCACCAAC 39872.8 HMGB1 AATTCAAAAAAGAAGATGATGATGATGAATACTCG 2474 chr13 ENST000003 AGTATTCATCATCATCATCTTCT 39872.8 HYAL2 AATTCAAAAACCTGCCAGTACCTCAAAGATTCTCGA 2475 chr3 ENST000003 GAATCTTTGAGGTACTGGCAGG 57750.8 HYAL2 AATTCAAAAACCTGCCAGTACCTCAAAGATTCTCGA 2476 chr3 ENST000003 GAATCTTTGAGGTACTGGCAGG 57750.8 HYAL2 AATTCAAAAACTGGACCTGAATGCCTTTGATCTCGA 2477 chr3 ENST000003 GATCAAAGGCATTCAGGTCCAG 57750.8 ICAM3 AATTCAAAAAGTCCAGCTCACGAGGCAAATACTCG 2478 chr19 ENST000001 AGTATTTGCCTCGTGAGCTGGAC 60262.9 ICAM3 AATTCAAAAACCAGCTCAACTTCAGCTAAATCTCGA 2479 chr19 ENST000001 GATTTAGCTGAAGTTGAGCTGG 60262.9 ICAM3 AATTCAAAAAGCACTTGAAATGGAAAGATAACTCG 2480 chr19 ENST000001 AGTTATCTTTCCATTTCAAGTGC 60262.9 ICAM3 AATTCAAAAAGAGCGGCAGTTACCATGTTAGCTCGA 2481 chr19 ENST000001 GCTAACATGGTAACTGCCGCTC 60262.9 ICOS AATTCAAAAAGCACGACCCTAACGGTGAATACTCG 2482 ch2 ENST000003 AGTATTCACCGTTAGGGTCGTGC 16386.10 ICOS AATTCAAAAAGTCCGCATTTCACTATCATACCTCGA 2483 ch2 ENST000003 GGTATGATAGTGAAATGCGGAC 16386.10 ICOS AATTCAAAAACCATTCTCATGCCAACTATTACTCGA 2484 ch2 ENST000003 GTAATAGTTGGCATGAGAATGG 16386.10 ICOS AATTCAAAAACACAGATGTGACCCTATAATACTCGA 2485 ch2 ENST000003 GTATTATAGGGTCACATCTGTG 16386.10 IFNA10 AATTCAAAAATGTAAAGAAGTGTCGTGTATACTCGA 2486 chr9 ENST000003 GTATACACGACACTTCTTTACA 57374.2 IFNA10 AATTCAAAAAATAACCACGACGCGTTGAATCCTCGA 2487 chr9 ENST000003 GGATTCAACGCGTCGTGGTTAT 57374.2 IFNA10 AATTCAAAAACCTGGGACAAATGGGAAGAATCTCG 2488 chr9 ENST000003 AGATTCTTCCCATTTGTCCCAGG 57374.2 IFNA14 AATTCAAAAACTGGGCTGTAATCTGTCTCAACTCGA 2489 chr9 ENST000003 GTTGAGACAGATTACAGCCCAG 80222.3 IFNA14 AATTCAAAAACCTGAATAACAGGAGGACTTTCTCGA 2490 chr9 ENST000003 GAAAGTCCTCCTGTTATTCAGG 80222.3 IFNA14 AATTCAAAAAGCAGCAGACCTTCAATCTCTTCTCGA 2491 chr9 ENST000003 GAAGAGATTGAAGGTCTGCTGC 80222.3 IFNA16 AATTCAAAAATGTAAAGAAGCATCGTGTTTACTCGA 2492 chr9 ENST000003 GTAAACACGATGCTTCTTTACA 80216.1 IFNA16 AATTCAAAAAATGATCCTCATTGATTAATACCTCGA 2493 chr9 ENST000003 GGTATTAATCAATGAGGATCAT 80216.1 IFNA16 AATTCAAAAACCTGAAGGACAGATATGATTTCTCGA 2494 chr9 ENST000003 GAAATCATATCTGTCCTTCAGG 80216.1 IFNA2 AATTCAAAAAGCACAGTGGTTAATGTAATAACTCGA 2495 chr9 ENST000003 GTTATTACATTAACCACTGTGC 80206.3 IFNA2 AATTCAAAAATATGACCATGACACGATTTAACTCGA 2496 chr9 ENST000003 GTTAAATCGTGTCATGGTCATA 80206.3 IFNA2 AATTCAAAAACCATGCTGACTGATCCATTATCTCGA 2497 chr9 ENST000003 GATAATGGATCAGTCAGCATGG 80206.3 IFNA5 AATTCAAAAAACTTGGGATGAGACACTTCTACTCGA 2498 chr9 ENST000006 GTAGAAGTGTCTCATCCCAAGT 10521.1 IFNA5 AATTCAAAAAAGTGGAAGACACTCCTCTGATCTCGA 2499 chr9 ENST000006 GATCAGAGGAGTGTCTTCCACT 10521.1 IFNA5 AATTCAAAAATCAACTGCAAGTCAATCTGTTCTCGA 2500 chr9 ENST000006 GAACAGATTGACTTGCAGTTGA 10521.1 IFNA6 AATTCAAAAAGACAGACATGACTTCAGATTTCTCGA 2501 chr9 ENST000003 GAAATCTGAAGTCATGTCTGTC 80210.1 IFNA6 AATTCAAAAACTGTCCTCCATGAGGTGATTCCTCGA 2502 chr9 ENST000003 GGAATCACCTCATGGAGGACAG 80210.1 IFNA6 AATTCAAAAAAGGCTTCTAGACAAACTCTATCTCGA 2503 chr9 ENST000003 GATAGAGTTTGTCTAGAAGCCT 80210.1 IFNA8 AATTCAAAAATAACTATCTATAGGGCTTAAACTCGA 2504 chr9 ENST000003 GTTTAAGCCCTATAGATAGTTA 80205.1 IFNA8 AATTCAAAAACCAGGAGGAGTTTGATGATAACTCG 2505 chr9 ENST000003 AGTTATCATCAAACTCCTCCTGG 80205.1 IFNA8 AATTCAAAAAGACCTGGTACAACACGGAAATCTCG 2506 chr9 ENST000003 AGATTTCCGTGTTGTACCAGGTC 80205.1 IFNAR1 AATTCAAAAAGCCAAGATTCAGGAAATTATTCTCGA 2507 chr21 ENST000002 GAATAATTTCCTGAATCTTGGC 70139.7 IFNAR1 AATTCAAAAAGCTCTCCCGTTTGTCATTTATCTCGA 2508 chr21 ENST000002 GATAAATGACAAACGGGAGAGC 70139.7 IFNAR1 AATTCAAAAAATGAACTGTGTCAAGTATAAGCTCGA 2509 chr21 ENST000002 GCTTATACTTGACACAGTTCAT 70139.7 IFNAR2 AATTCAAAAAGAGTGGAAATTTCACCTATATCTCGA 2510 chr21 ENST000003 GATATAGGTGAAATTTCCACTC 42136.8 IFNAR2 AATTCAAAAATGTATATCAGCCTCGTGTTTGCTCGA 2511 chr21 ENST000003 GCAAACACGAGGCTGATATACA 42136.8 IFNAR2 AATTCAAAAAGCAAATACCACAAGATCATTTCTCGA 2512 chr21 ENST000003 GAAATGATCTTGTGGTATTTGC 42136.8 IFNB1 AATTCAAAAAATTGAATGGGAGGCTTGAATACTCG 2513 chr9 ENST000003 AGTATTCAAGCCTCCCATTCAAT 80232.3 IFNB1 AATTCAAAAACCTACAAAGAAGCAGCAATTTCTCG 2514 chr9 ENST000003 AGAAATTGCTGCTTCTTTGTAGG 80232.3 IFNB1 AATTCAAAAACTAATGTCTATCATCAGATAACTCGA 2515 chr9 ENST000003 GTTATCTGATGATAGACATTAG 80232.3 IFNE AATTCAAAAAGGTAGTGATAACCTTAGATTACTCGA 2516 chr9 ENST000004 GTAATCTAAGGTTATCACTACC 48696.4 IFNE AATTCAAAAAAGCCTCTTCAGGGCAAATATTCTCGA 2517 chr9 ENST000004 GAATATTTGCCCTGAAGAGGCT 48696.4 IFNE AATTCAAAAACATAGAGTGGTAATACAATTTCTCGA 2518 chr9 ENST000004 GAAATTGTATTACCACTCTATG 48696.4 IFNG AATTCAAAAAGGTTGTCCTGCCTGCAATATTCTCGA 2519 chr12 ENST000002 GAATATTGCAGGCAGGACAACC 29135.3 IFNG AATTCAAAAACATTCAGATGTAGCGGATAATCTCGA 2520 chr12 ENST000002 GATTATCCGCTACATCTGAATG 29135.3 IFNG AATTCAAAAATGTTACTGCCAGGACCCATATCTCGA 2521 chr12 ENST000002 GATATGGGTCCTGGCAGTAACA 29135.3 IFNGR1 AATTCAAAAAACGAGCAGGAAGTCGATTATGCTCG 2522 chr6 ENST000003 AGCATAATCGACTTCCTGCTCGT 67739.8 IFNGR1 AATTCAAAAACATGAACCCTATCGTATATTGCTCGA 2523 chr6 ENST000003 GCAATATACGATAGGGTTCATG 67739.8 IFNGR1 AATTCAAAAACGGAAGTGAGATCCAGTATAACTCG 2524 chr6 ENST000003 AGTTATACTGGATCTCACTTCCG 67739.8 IFNK AATTCAAAAAGAGATTGTGGCTACGCAAATGCTCG 2525 chr9 ENST000002 AGCATTTGCGTAGCCACAATCTC 76943.2 IFNK AATTCAAAAACTGTTCAGATTCAAGATTATTCTCGA 2526 chr9 ENST000002 GAATAATCTTGAATCTGAACAG 76943.2 IFNK AATTCAAAAATCAGCCAACACACCTTCAAATCTCGA 2527 chr9 ENST000002 GATTTGAAGGTGTGTTGGCTGA 76943.2 IFNL1 AATTCAAAAACTCACGCGAGACCTCAAATATCTCGA 2528 chr19 ENST000003 GATATTTGAGGTCTCGCGTGAG 33625.2 IFNL1 AATTCAAAAAGCCACATTGGCAGGTTCAAATCTCGA 2529 chr19 ENST000003 GATTTGAACCTGCCAATGTGGC 33625.2 IFNL1 AATTCAAAAAGAGTTGCAGCTCTCCTGTCTTCTCGA 2530 chr19 ENST000003 GAAGACAGGAGAGCTGCAACTC 33625.2 IFNL3 AATTCAAAAAAGGGCCAAAGATGCCTTAGAACTCG 2531 chr19 ENST000004 AGTTCTAAGGCATCTTTGGCCCT 13851.2 IFNL3 AATTCAAAAAGCCTTTAAGAGGGCCAAAGATCTCG 2532 chr19 ENST000004 AGATCTTTGGCCCTCTTAAAGGC 13851.2 IFNL3 AATTCAAAAATGCCACATAGCCCAGTTCAAGCTCGA 2533 chr19 ENST000004 GCTTGAACTGGGCTATGTGGCA 13851.2 IFNW1 AATTCAAAAAAGACTCTTATTTCGGCTTTAACTCGA 2534 chr9 ENST000003 GTTAAAGCCGAAATAAGAGTCT 80229.3

IFNW1 AATTCAAAAATCAGTCCCTAAGATGTTATTTCTCGA 2535 chr9 ENST000003 GAAATAACATCTTAGGGACTGA 80229.3 IFNW1 AATTCAAAAACGGTATATTAAGCCAGTATATCTCGA 2536 chr9 ENST000003 GATATACTGGCTTAATATACCG 80229.3 IL10 AATTCAAAAAAGCTTCTCTGTGAACGATTTACTCGA 2537 chr1 ENST000004 GTAAATCGTTCACAGAGAAGCT 23557.1 IL10 AATTCAAAAAGCAGGTGAAGAATGCCTTTAACTCG 2538 chr1 ENST000004 AGTTAAAGGCATTCTTCACCTGC 23557.1 IL10 AATTCAAAAAGCTGGACAACTTGTTGTTAAACTCGA 2539 chr1 ENST000004 GTTTAACAACAAGTTGTCCAGC 23557.1 IL10RA AATTCAAAAATCTGTCGCTTCCCGAAGTAACCTCGA 2540 chr11 ENST000002 GGTTACTTCGGGAAGCGACAGA 27752.7 IL10RA AATTCAAAAAGAAACAGGATCCTCTAGAAATCTCG 2541 chr11 ENST000002 AGATTTCTAGAGGATCCTGTTTC 27752.7 IL10RA AATTCAAAAAGAACTCTTTCCTGTATCATAACTCGA 2542 chr11 ENST000002 GTTATGATACAGGAAAGAGTTC 27752.7 IL11 AATTCAAAAAATATCCACTTGAGGGCGATTTCTCGA 2543 chr19 ENST000002 GAAATCGCCCTCAAGTGGATAT 64563.6 IL11 AATTCAAAAACCTTCCAAAGCCAGATCTTATCTCGA 2544 chr19 ENST000002 GATAAGATCTGGCTTTGGAAGG 64563.6 IL11 AATTCAAAAATGCACAGCTGAGGGACAAATTCTCG 2545 chr19 ENST000002 AGAATTTGTCCCTCAGCTGTGCA 64563.6 IL11RA AATTCAAAAACGGCAGATTCCACCTATAATTCTCGA 2546 chr9 ENST000003 GAATTATAGGTGGAATCTGCCG 18041.13 IL11RA AATTCAAAAATCGGCAGATTCCACCTATAATCTCGA 2547 chr9 ENST000003 GATTATAGGTGGAATCTGCCGA 18041.13 IL11RA AATTCAAAAATGGAGCCAGTACCGGATTAATCTCGA 2548 chr9 ENST000003 GATTAATCCGGTACTGGCTCCA 18041.13 IL12A AATTCAAAAATGATACCTCTGATCAAGTATTCTCGA 2549 chr3 ENST000003 GAATACTTGATCAGAGGTATCA 05579.6 IL12A AATTCAAAAACCTGTGCCTTAGTAGTATTTACTCGA 2550 chr3 ENST000003 GTAAATACTACTAAGGCACAGG 05579.6 IL12A AATTCAAAAACCTGTTTACCATTGGAATTAACTCGA 2551 chr3 ENST000003 GTTAATTCCAATGGTAAACAGG 05579.6 IL12B AATTCAAAAAGAATTTGGTCCACTGATATTTCTCGA 2552 chr5 ENST000002 GAAATATCAGTGGACCAAATTC 31228.2 IL12B AATTCAAAAACCATGGGCCTTCATGCTATTTCTCGA 2553 chr5 ENST000002 GAAATAGCATGAAGGCCCATGG 31228.2 IL12B AATTCAAAAATTAGATGCTAAATGCTCATTGCTCGA 2554 chr5 ENST000002 GCAATGAGCATTTAGCATCTAA 31228.2 IL12RB1 AATTCAAAAACAGCTCTACAACTCAGTTAAACTCGA 2555 chr19 ENST000005 GTTTAACTGAGTTGTAGAGCTG 93993.6 IL12RB1 AATTCAAAAAGTCATCTCCTCGAACCAATTTCTCGA 2556 chr19 ENST000005 GAAATTGGTTCGAGGAGATGAC 93993.6 IL12RB1 AATTCAAAAACCAACGGGACCACCATGTATTCTCGA 2557 chr19 ENST000005 GAATACATGGTGGTCCCGTTGG 93993.6 IL13 AATTCAAAAAACTTCGAAAGCATCATTATTTCTCGA 2558 chr5 ENST000003 GAAATAATGATGCTTTCGAAGT 04506.7 IL13 AATTCAAAAAATTGAAGTTGCAGATTCATTTCTCGA 2559 chr5 ENST000003 GAAATGAATCTGCAACTTCAAT 04506.7 IL13 AATTCAAAAACCTGCTCTTACATTTAAAGAACTCGA 2560 chr5 ENST000003 GTTCTTTAAATGTAAGAGCAGG 04506.7 IL15 AATTCAAAAAGAAGATCTTATTCAATCTATGCTCGA 2561 chr4 ENST000002 GCATAGATTGAATAAGATCTTC 96545.11 IL15 AATTCAAAAATAAGGGTGATAGTCAAATTATCTCGA 2562 chr4 ENST000002 GATAATTTGACTATCACCCTTA 96545.11 IL15 AATTCAAAAACACTCTGCTGCTTAGACATAACTCGA 2563 chr4 ENST000002 GTTATGTCTAAGCAGCAGAGTG 96545.11 IL16 AATTCAAAAATGGGACCACGTGAGATCATTCCTCGA 2564 chr15 ENST000003 GGAATGATCTCACGTGGTCCCA 02987.8 IL16 AATTCAAAAAGTTCTGGATGAAGCAACATTACTCGA 2565 chr15 ENST000003 GTAATGTTGCTTCATCCAGAAC 02987.8 IL16 AATTCAAAAACCCAAACAGTGACATTTATTTCTCGA 2566 chr15 ENST000003 GAAATAAATGTCACTGTTTGGG 02987.8 IL17A AATTCAAAAAATCAGTTCTGCCTAGGTAAATCTCGA 2567 chr6 ENST000003 GATTTACCTAGGCAGAACTGAT 40057.1 IL17A AATTCAAAAAGAGCTATTTAAGGATCTATTTCTCGA 2568 chr6 ENST000003 GAAATAGATCCTTAAATAGCTC 40057.1 IL17A AATTCAAAAAGGTCAACCTGAACATCCATAACTCGA 2569 chr6 ENST000003 GTTATGGATGTTCAGGTTGACC 40057.1 IL17B AATTCAAAAATATGCCCGCATGGAGGAGTATCTCGA 2570 chr5 ENST000002 GATACTCCTCCATGCGGGCATA 61796.3 IL17B AATTCAAAAAGTGTCACGGATGAAACCGTATCTCGA 2571 chr5 ENST000002 GATACGGTTTCATCCGTGACAC 61796.3 IL17B AATTCAAAAAGCAGCTGTGGATGTCCAACAACTCG 2572 chr5 ENST000002 AGTTGTTGGACATCCACAGCTGC 61796.3 IL17C AATTCAAAAAGCACCTCTTCCAGCCCTTAAACTCGA 2573 chr16 ENST000002 GTTTAAGGGCTGGAAGAGGTGC 44241.4 IL17C AATTCAAAAACTTTGCCTTCCACACCGAGTTCTCGA 2574 chr16 ENST000002 GAACTCGGTGTGGAAGGCAAAG 44241.4 IL17C AATTCAAAAAATCTCCAGCCTCAGTAGTTGGCTCGA 2575 chr16 ENST000002 GCCAACTACTGAGGCTGGAGAT 44241.4 IL17D AATTCAAAAAAGAGCTACTCTGTTACATTTCCTCGA 2576 chr13 ENST000003 GGAAATGTAACAGAGTAGCTCT 04920.3 IL17D AATTCAAAAACAAAGAGATAGGGACGCATATCTCG 2577 chr13 ENST000003 AGATATGCGTCCCTATCTCTTTG 04920.3 IL17D AATTCAAAAAAGACAGCATCAACTCCAGCATCTCG 2578 chr13 ENST000003 AGATGCTGGAGTTGATGCTGTCT 04920.3 IL17F AATTCAAAAATCATCCACCATGTGCAGTAAGCTCGA 2579 chr6 ENST000003 GCTTACTGCACATGGTGGATGA 36123.4 IL17F AATTCAAAAAGTACTTGCTGCTGTCGATATTCTCGA 2580 chr6 ENST000003 GAATATCGACAGCAGCAAGTAC 36123.4 IL17F AATTCAAAAACGTTTCCATGTCACGTAACATCTCGA 2581 chr6 ENST000003 GATGTTACGTGACATGGAAACG 36123.4 IL18 AATTCAAAAACCCGGACCATATTTATTATAACTCGA 2582 chr11 ENST000002 GTTATAATAAATATGGTCCGGG 80357.11 IL18 AATTCAAAAATGATTCTGACTGTAGAGATAACTCGA 2583 chr11 ENST000002 GTTATCTCTACAGTCAGAATCA 80357.11 IL18 AATTCAAAAATGGCAAGCTTGAATCTAAATTCTCGA 2584 chr11 ENST000002 GAATTTAGATTCAAGCTTGCCA 80357.11 IL18BP AATTCAAAAAGGTCCCTTCTCTCACCAAATTCTCGA 2585 chr11 ENST000002 GAATTTGGTGAGAGAAGGGACC 60049.9 IL18BP AATTCAAAAATCCCATGTCTCTGCTCATTTACTCGA 2586 chr11 ENST000002 GTAAATGAGCAGAGACATGGGA 60049.9 IL18BP AATTCAAAAACTGGGCAATGGTTCCTTCATTCTCGA 2587 chr11 ENST000002 GAATGAAGGAACCATTGCCCAG 60049.9 IL19 AATTCAAAAAGTCCACGCTGCTGCCATTAAACTCGA 2588 chr1 ENST000002 GTTTAATGGCAGCAGCGTGGAC 70218.10 IL19 AATTCAAAAATCCACAGACATGCACCATATACTCGA 2589 chr1 ENST000002 GTATATGGTGCATGTCTGTGGA 70218.10 IL19 AATTCAAAAATGATGACAAGGAACCTGTATACTCG 2590 chr1 ENST000002 AGTATACAGGTTCCTTGTCATCA 70218.10 IL1A AATTCAAAAAGTGGAACCAACACTAACATATCTCG 2591 chr2 ENST000002 AGATATGTTAGTGTTGGTTCCAC 63339.3 IL1A AATTCAAAAAGCCCTCAATCAAAGTATAATTCTCGA 2592 chr2 ENST000002 GAATTATACTTTGATTGAGGGC 63339.3 IL1A AATTCAAAAATATTACAGATGGGCAAATTAACTCGA 2593 chr2 ENST000002 GTTAATTTGCCCATCTGTAATA 63339.3 IL1B AATTCAAAAAATCAATAACAAGCTGGAATTTCTCGA 2594 chr2 ENST000002 GAAATTCCAGCTTGTTATTGAT 63341.6 IL1B AATTCAAAAAAGCAACCGCTTCCCTATTTATCTCGA 2595 chr2 ENST000002 GATAAATAGGGAAGCGGTTGCT 63341.6 IL1B AATTCAAAAACTGACTTCACCATGCAATTTGCTCGA 2596 chr2 ENST000002 GCAAATTGCATGGTGAAGTCAG 63341.6 IL1F10 AATTCAAAAATCCTTGTGGGCTCAGTTTAATCTCGA 2597 chr2 ENST000003 GATTAAACTGAGCCCACAAGGA 41010.6 IL1F10 AATTCAAAAAGGTCTATGGTAGGCAGAATAACTCG 2598 chr2 ENST000003 AGTTATTCTGCCTACCATAGACC 41010.6 IL1F10 AATTCAAAAATGCAGACCAGAAGGCTCTATACTCG 2599 chr2 ENST000003 AGTATAGAGCCTTCTGGTCTGCA 41010.6 IL1R1 AATTCAAAAAGCCAAGAATACACATGGTATACTCG 2600 chr2 ENST000004 AGTATACCATGTGTATTCTTGGC 10023.5 IL1R1 AATTCAAAAAATAATGCACAAGCCATATTTACTCGA 2601 chr2 ENST000004 GTAAATATGGCTTGTGCATTAT 10023.5 IL1R1 AATTCAAAAATGGTATAGATGCAGCATATATCTCGA 2602 chr2 ENST000004 GATATATGCTGCATCTATACCA 10023.5 IL1R2 AATTCAAAAACAATCCCGTGTAAGGTGTTTCCTCGA 2603 chr2 ENST000003 GGAAACACCTTACACGGGATTG 32549.7 IL1R2 AATTCAAAAAGACCATTCCTGTGATCATTTCCTCGA 2604 chr2 ENST000003 GGAAATGATCACAGGAATGGTC 32549.7 IL1R2 AATTCAAAAACGTTCATCTCATACCCGCAAACTCGA 2605 chr2 ENST000003 GTTTGCGGGTATGAGATGAACG 32549.7 IL1RAPL1 AATTCAAAAACAAAGCAAGCGGCTGATTATTCTCGA 2606 chrX ENST000003 GAATAATCAGCCGCTTGCTTTG 78993.5 IL1RAPL1 AATTCAAAAAGCCAGCGTTCTCCTTCATAAACTCGA 2607 chrX ENST000003 GTTTATGAAGGAGAACGCTGGC 78993.5 IL1RAPL1 AATTCAAAAATCAAGCTCCTGACGGTCATTACTCGA 2608 chrX ENST000003 GTAATGACCGTCAGGAGCTTGA 78993.5 IL1RL1 AATTCAAAAATTACACCGTGGATTGGTATTACTCGA 2609 chr2 ENST000002 GTAATACCAATCCACGGTGTAA 33954.5 IL1RL1 AATTCAAAAAAGTTGCTGATTCTGGTATTTACTCGA 2610 chr2 ENST000002 GTAAATACCAGAATCAGCAACT 33954.5 IL1RL1 AATTCAAAAACGTGAAGGAAGAGGATTTATTCTCG 2611 chr2 ENST000002 AGAATAAATCCTCTTCCTTCACG 33954.5 IL1RN AATTCAAAAAGCAAGGACCAAATGTCAATTTCTCGA 2612 chr2 ENST000004 GAAATTGACATTTGGTCCTTGC 09930.3 IL1RN AATTCAAAAACGTCATGGTCACCAAATTCTACTCGA 2613 chr2 ENST000004 GTAGAATTTGGTGACCATGACG 09930.3 IL1RN AATTCAAAAACTGCCTCCAGAATGGTCTTTCCTCGA 2614 chr2 ENST000004 GGAAAGACCATTCTGGAGGCAG 09930.3 IL2 AATTCAAAAAGCTACCTATTGTAACTATTATCTCGA 2615 chr4 ENST000002 GATAATAGTTACAATAGGTAGC 26730.4 IL2 AATTCAAAAACAGCTACAACTGGAGCATTTACTCGA 2616 chr4 ENST000002 GTAAATGCTCCAGTTGTAGCTG 26730.4 IL2 AATTCAAAAATGCTGGATTTACAGATGATTTCTCGA 2617 chr4 ENST000002 GAAATCATCTGTAAATCCAGCA 26730.4 IL20 AATTCAAAAACTGATGCTCTGTGAGATATTTCTCGA 2618 chr1 ENST000003 GAAATATCTCACAGAGCATCAG 67096.7

IL20 AATTCAAAAATGGTCACAGTGTATCTTATTTCTCGA 2619 chr1 ENST000003 GAAATAAGATACACTGTGACCA 67096.7 IL20 AATTCAAAAAGGACTGAAGACACTCAATTTGCTCGA 2620 chr1 ENST000003 GCAAATTGAGTGTCTTCAGTCC 67096.7 IL20RA AATTCAAAAACCAGTATTATGCCAAAGTTAACTCGA 2621 chr6 ENST000003 GTTAACTTTGGCATAATACTGG 16649.9 IL20RA AATTCAAAAAGAGGGTCTTCAAGGAGTTAAACTCG 2622 chr6 ENST000003 AGTTTAACTCCTTGAAGACCCTC 16649.9 IL20RA AATTCAAAAAGCTTCGCATTTGATGGAAATTCTCGA 2623 chr6 ENST000003 GAATTTCCATCAAATGCGAAGC 16649.9 IL20RB AATTCAAAAACAGTGTACTATTCTGTCGAATCTCGA 2624 chr3 ENST000003 GATTCGACAGAATAGTACACTG 29582.8 IL20RB AATTCAAAAACCAGAATAATCCTTGAGAGAACTCG 2625 chr3 ENST000003 AGTTCTCTCAAGGATTATTCTGG 29582.8 IL20RB AATTCAAAAACTCTGTACTCTCAACCAACATCTCGA 2626 chr3 ENST000003 GATGTTGGTTGAGAGTACAGAG 29582.8 IL21 AATTCAAAAAAGGAAACCACCTTCCACAAATCTCG 2627 chr4 ENST000002 AGATTTGTGGAAGGTGGTTTCCT 64497.7 IL21 AATTCAAAAAATGACTTGGTCCCTGAATTTCCTCGA 2628 chr4 ENST000002 GGAAATTCAGGGACCAAGTCAT 64497.7 IL21 AATTCAAAAACTTTCAGAAGGCCCAACTAAACTCGA 2629 chr4 ENST000002 GTTTAGTTGGGCCTTCTGAAAG 64497.7 IL22 AATTCAAAAAAGGCTAAGCACATGTCATATTCTCGA 2630 chr12 ENST000003 GAATATGACATGTGCTTAGCCT 28087.5 IL22 AATTCAAAAAGTTTCCATAATCAGTACTTTACTCGA 2631 chr12 ENST000003 GTAAAGTACTGATTATGGAAAC 28087.5 IL22 AATTCAAAAAAGACTTTCTAAGCATAGATATCTCGA 2632 chr12 ENST000003 GATATCTATGCTTAGAAAGTCT 28087.5 IL22RA1 AATTCAAAAAGGACACTTTCTAGTCCTAAACCTCGA 2633 chr1 ENST000002 GGTTTAGGACTAGAAAGTGTCC 70800.1 IL22RA1 AATTCAAAAAAGGGACACCACAGTACCTAAACTCG 2634 chr1 ENST000002 AGTTTAGGTACTGTGGTGTCCCT 70800.1 IL22RA1 AATTCAAAAACTGTCCGAGATCACCTACTTACTCGA 2635 chr1 ENST000002 GTAAGTAGGTGATCTCGGACAG 70800.1 IL22RA2 AATTCAAAAAAGACATACAGGAACCTTATTACTCGA 2636 chr6 ENST000003 GTAATAAGGTTCCTGTATGTCT 49184.8 IL22RA2 AATTCAAAAACTCGTGTTTGAAGGATCTTATCTCGA 2637 chr6 ENST000003 GATAAGATCCTTCAAACACGAG 49184.8 IL22RA2 AATTCAAAAATGCTCCAAATTTACCATATAGCTCGA 2638 chr6 ENST000003 GCTATATGGTAAATTTGGAGCA 49184.8 IL23A AATTCAAAAAAGCTGCTAGGATCGGATATTTCTCGA 2639 chr12 ENST000002 GAAATATCCGATCCTAGCAGCT 28534.5 IL23A AATTCAAAAACTGTGAGCCAACAGGTTAATTCTCGA 2640 chr12 ENST000002 GAATTAACCTGTTGGCTCACAG 28534.5 IL23A AATTCAAAAAGGATCCACCAGGGTCTGATTTCTCGA 2641 chr12 ENST000002 GAAATCAGACCCTGGTGGATCC 28534.5 IL23R AATTCAAAAACTTTCTTTGATTGGGATATTTCTCGA 2642 chr1 ENST000003 GAAATATCCCAATCAAAGAAAG 47310.9 IL23R AATTCAAAAATATCTCACCTCAAGCTATATTCTCGA 2643 chr1 ENST000003 GAATATAGCTTGAGGTGAGATA 47310.9 IL23R AATTCAAAAACGACAATACTACAGTTGTATACTCGA 2644 chr1 ENST000003 GTATACAACTGTAGTATTGTCG 47310.9 IL24 AATTCAAAAACACAGGCGGTTTCTGCTATTCCTCGA 2645 chr1 ENST000002 GGAATAGCAGAAACCGCCTGTG 94984.6 IL24 AATTCAAAAAGTCAGGACTCTGAAGTCATTCCTCGA 2646 chr1 ENST000002 GGAATGACTTCAGAGTCCTGAC 94984.6 IL24 AATTCAAAAATCGGATGCTGAGAGCTGTTACCTCGA 2647 chr1 ENST000002 GGTAACAGCTCTCAGCATCCGA 94984.6 IL25 AATTCAAAAAACAGGCACTTTCTAGATATTTCTCGA 2648 chr14 ENST000003 GAAATATCTAGAAAGTGCCTGT 29715.2 IL25 AATTCAAAAACCACAACCAGACTGTCTTCTACTCGA 2649 chr14 ENST000003 GTAGAAGACAGTCTGGTTGTGG 29715.2 IL25 AATTCAAAAATCCTGTAGGGCCAGTGAAGATCTCGA 2650 chr14 ENST000003 GATCTTCACTGGCCCTACAGGA 29715.2 IL26 AATTCAAAAAAGCTGTTGACGCTCTCTATATCTCGA 2651 chr12 ENST000002 GATATAGAGAGCGTCAACAGCT 29134.4 IL26 AATTCAAAAAAGTACATTGTGTCAACTTAATCTCGA 2652 chr12 ENST000002 GATTAAGTTGACACAATGTACT 29134.4 IL26 AATTCAAAAACGATTCCAGAAGACCGCATAACTCG 2653 chr12 ENST000002 AGTTATGCGGTCTTCTGGAATCG 29134.4 IL27 AATTCAAAAAACTCCTTGGAGCTCGTCTTATCTCGA 2654 chr16 ENST000003 GATAAGACGAGCTCCAAGGAGT 56897.1 IL27 AATTCAAAAAACTTTAGGACTGGAGTCTTGGCTCGA 2655 chr16 ENST000003 GCCAAGACTCCAGTCCTAAAGT 56897.1 IL27 AATTCAAAAACATCATCAGCCTTGGACAAGGCTCGA 2656 chr16 ENST000003 GCCTTGTCCAAGGCTGATGATG 56897.1 IL2RA AATTCAAAAACCTCGTCACAACAACAGATTTCTCGA 2657 chr10 ENST000003 GAAATCTGTTGTTGTGACGAGG 79959.7 IL2RA AATTCAAAAAACCCTATACAACTGGACATTGCTCGA 2658 chr10 ENST000003 GCAATGTCCAGTTGTATAGGGT 79959.7 IL2RA AATTCAAAAAACTCGGAACACAACGAAACAACTCG 2659 chr10 ENST000003 AGTTGTTTCGTTGTGTTCCGAGT 79959.7 IL2RB AATTCAAAAAAGTCCCAGACCTGGTGGATTTCTCGA 2660 chr22 ENST000002 GAAATCCACCAGGTCTGGGACT 16223.9 IL2RB AATTCAAAAAGACCCACAGATGCAACATAAGCTCG 2661 chr22 ENST000002 AGCTTATGTTGCATCTGTGGGTC 16223.9 IL2RB AATTCAAAAACCAGACACCCAGTATGAGTTTCTCGA 2662 chr22 ENST000002 GAAACTCATACTGGGTGTCTGG 16223.9 IL2RG AATTCAAAAATCGTGTTCGGAGCCGCTTTAACTCGA 2663 chrX ENST000003 GTTAAAGCGGCTCCGAACACGA 74202.6 IL2RG AATTCAAAAACCAACCTCACTCTGCATTATTCTCGA 2664 chrX ENST000003 GAATAATGCAGAGTGAGGTTGG 74202.6 IL2RG AATTCAAAAATTGGCTCCATGGGATTGATTACTCGA 2665 chrX ENST000003 GTAATCAATCCCATGGAGCCAA 74202.6 IL3 AATTCAAAAATTATCCCATTGAGACTATTTACTCGA 2666 chr5 ENST000002 GTAAATAGTCTCAATGGGATAA 96870.2 IL3 AATTCAAAAACGGCATCAGATGAATTGTTAACTCGA 2667 chr5 ENST000002 GTTAACAATTCATCTGATGCCG 96870.2 IL3 AATTCAAAAAGCAATTGAGAGCATTCTTAAACTCGA 2668 chr5 ENST000002 GTTTAAGAATGCTCTCAATTGC 96870.2 IL31 AATTCAAAAAGCATATCTCAAGACAATCAGACTCG 2669 chr12 ENST000003 AGTCTGATTGTCTTGAGATATGC 77035.1 IL31 AATTCAAAAACCAAGTGATGATGTACAGAAACTCG 2670 chr12 ENST000003 AGTTTCTGTACATCATCACTTGG 77035.1 IL31 AATTCAAAAACCTGACTATTTCTCAACAGTTCTCGA 2671 chr12 ENST000003 GAACTGTTGAGAAATAGTCAGG 77035.1 IL31RA AATTCAAAAACATCAAACGAATGATTCAAATCTCGA 2672 chr5 ENST000004 GATTTGAATCATTCGTTTGATG 47346.6 IL31RA AATTCAAAAACGCCTGTTTCATCTGATTTAACTCGA 2673 chr5 ENST000004 GTTAAATCAGATGAAACAGGCG 47346.6 IL31RA AATTCAAAAATTTCCTGTGTCTACTACTATACTCGA 2674 chr5 ENST000004 GTATAGTAGTAGACACAGGAAA 47346.6 IL32 AATTCAAAAATGTCGCCCTGGCATCTTAATACTCGA 2675 chr16 ENST000003 GTATTAAGATGCCAGGGCGACA 25568.9 IL32 AATTCAAAAAAGAGCTCACTCCTCTACTTGACTCGA 2676 chr16 ENST000003 GTCAAGTAGAGGAGTGAGCTCT 25568.9 IL32 AATTCAAAAAAGAGCTGGAGGACGACTTCAACTCG 2677 chr16 ENST000003 AGTTGAAGTCGTCCTCCAGCTCT 25568.9 IL33 AATTCAAAAAGAGTGCTTTGCCTTTGGTATACTCGA 2678 chr9 ENST000003 GTATACCAAAGGCAAAGCACTC 81434.7 IL33 AATTCAAAAAGCACTCCAACTGTGTTTCATTCTCGA 2679 chr9 ENST000003 GAATGAAACACAGTTGGAGTGC 81434.7 IL33 AATTCAAAAACCTGTTACTTTAGGAGAGAAACTCGA 2680 chr9 ENST000003 GTTTCTCTCCTAAAGTAACAGG 81434.7 IL34 AATTCAAAAAGCCGACTTCAGTACATGAAACCTCGA 2681 chr16 ENST000002 GGTTTCATGTACTGAAGTCGGC 88098.6 IL34 AATTCAAAAACAGAGCCCTCATTGCAGTATGCTCGA 2682 chr16 ENST000002 GCATACTGCAATGAGGGCTCTG 88098.6 IL34 AATTCAAAAACCGTGTTGTCCCTCTTGAATGCTCGA 2683 chr16 ENST000002 GCATTCAAGAGGGACAACACGG 88098.6 IL36A AATTCAAAAACTCCAGTCACTATTGCCTTAACTCGA 2684 chr2 ENST000002 GTTAAGGCAATAGTGACTGGAG 59211.6 IL36A AATTCAAAAATTCAGGACCAGACGCTCATAGCTCGA 2685 chr2 ENST000002 GCTATGAGCGTCTGGTCCTGAA 59211.6 IL36A AATTCAAAAACTCTGCCTGATGTGTGCTAAACTCGA 2686 chr2 ENST000002 GTTTAGCACACATCAGGCAGAG 59211.6 IL36B AATTCAAAAAATCCTATGCTATTCGTGATTCCTCGA 2687 chr2 ENST000003 GGAATCACGAATAGCATAGGAT 27407.2 IL36B AATTCAAAAACCTGAGTGGAAATTCTTTAATCTCGA 2688 chr2 ENST000003 GATTAAAGAATTTCCACTCAGG 27407.2 IL36B AATTCAAAAATTGGACTACATAACCTGTAAACTCGA 2689 chr2 ENST000003 GTTTACAGGTTATGTAGTCCAA 27407.2 IL36G AATTCAAAAATGATATCATCCAGTCTTTATACTCGA 2690 chr2 ENST000002 GTATAAAGACTGGATGATATCA 59205.4 IL36G AATTCAAAAACAGGAGAGCTGGGTGGTATAACTCG 2691 chr2 ENST000002 AGTTATACCACCCAGCTCTCCTG 59205.4 IL36G AATTCAAAAAGGGAATCCAGAATCCAGAAATCTCG 2692 chr2 ENST000002 AGATTTCTGGATTCTGGATTCCC 59205.4 IL36RN AATTCAAAAACTCGGCATTGAAGGTGCTTTACTCGA 2693 chr2 ENST000003 GTAAAGCACCTTCAATGCCGAG 46807.7 IL36RN AATTCAAAAATGGTTCCCAGTTTGGATAAATCTCGA 2694 chr2 ENST000003 GATTTATCCAAACTGGGAACCA 46807.7 IL36RN AATTCAAAAAGGGAATCATTCCTGCTTAATGCTCGA 2695 chr2 ENST000003 GCATTAAGCAGGAATGATTCCC 46807.7 IL37 AATTCAAAAACTCTACTGTGACAAGGATAAACTCGA 2696 chr2 ENST000002 GTTTATCCTTGTCACAGTAGAG 63326.7 IL37 AATTCAAAAATGCACCTCCTGCAATTGTAATCTCGA 2697 chr2 ENST000002 GATTACAATTGCAGGAGGTGCA 63326.7 IL37 AATTCAAAAAGTTCACACAAAGATCTTCTTTCTCGA 2698 chr2 ENST000002 GAAAGAAGATCTTTGTGTGAAC 63326.7 IL4 AATTCAAAAAAGCTGATCCGATTCCTGAAACCTCGA 2699 chr5 ENST000002 GGTTTCAGGAATCGGATCAGCT 31449.6 IL4 AATTCAAAAACCACGGACACAAGTGCGATATCTCG 2700 chr5 ENST000002 AGATATCGCACTTGTGTCCGTGG 31449.6 IL4 AATTCAAAAATAGCATGTGCCGGCAACTTTGCTCGA 2701 chr5 ENST000002 GCAAAGTTGCCGGCACATGCTA 31449.6 IL5 AATTCAAAAAGCAAGAGTTTCTTGGTGTAATCTCGA 2702 chr5 ENST000002

GATTACACCAAGAAACTCTTGC 31454.5 IL5 AATTCAAAAAGGGTACTGTGGAAAGACTATTCTCGA 2703 chr5 ENST000002 GAATAGTCTTTCCACAGTACCC 31454.5 IL5 AATTCAAAAAGAAAGAGTCAGGCCTTAATTTCTCGA 2704 chr5 ENST000002 GAAATTAAGGCCTGACTCTTTC 31454.5 IL6 AATTCAAAAAATGAGCGTTAGGACACTATTTCTCGA 2705 chr7 ENST000002 GAAATAGTGTCCTAACGCTCAT 58743.9 IL6 AATTCAAAAAGAGTACCTCCAGAACAGATTTCTCGA 2706 chr7 ENST000002 GAAATCTGTTCTGGAGGTACTC 58743.9 IL6 AATTCAAAAAATGTGAAGCTGAGTTAATTTACTCGA 2707 chr7 ENST000002 GTAAATTAACTCAGCTTCACAT 58743.9 IL6R AATTCAAAAAGCAGGCACTTACTACTAATAACTCGA 2708 chr1 ENST000003 GTTATTAGTAGTAAGTGCCTGC 68485.7 IL6R AATTCAAAAATATCGGGCTGAACGGTCAAAGCTCG 2709 chr1 ENST000003 AGCTTTGACCGTTCAGCCCGATA 68485.7 IL6R AATTCAAAAACTGGACCCTGTGGATGATAAACTCGA 2710 chr1 ENST000003 GTTTATCATCCACAGGGTCCAG 68485.7 IL6ST AATTCAAAAAACCGTGCATCGCACCTATTTACTCGA 2711 chr5 ENST000003 GTAAATAGGTGCGATGCACGGT 36909.9 IL6ST AATTCAAAAAACTTCAGCAGTACCTATAAAGCTCGA 2712 chr5 ENST000003 GCTTTATAGGTACTGCTGAAGT 36909.9 IL6ST AATTCAAAAACGGCCAGAAGATCTACAATTACTCG 2713 chr5 ENST000003 AGTAATTGTAGATCTTCTGGCCG 36909.9 IL7 AATTCAAAAAGCTCGCAAGTTGAGGCAATTTCTCGA 2714 chr8 ENST000002 GAAATTGCCTCAACTTGCGAGC 63851.8 IL7 AATTCAAAAAGCTCACTATGAATCTATTATACTCGA 2715 chr8 ENST000002 GTATAATAGATTCATAGTGAGC 63851.8 IL7 AATTCAAAAAGTGTTTCCTAAAGAGACTATTCTCGA 2716 chr8 ENST000002 GAATAGTCTCTTTAGGAAACAC 63851.8 IL9 AATTCAAAAAACCACCATGCAAACAAGATACCTCG 2717 chr5 ENST000002 AGGTATCTTGTTTGCATGGTGGT 74520.1 IL9 AATTCAAAAAGAACAACAAGTGTCCATATTTCTCGA 2718 chr5 ENST000002 GAAATATGGACACTTGTTGTTC 74520.1 IL9 AATTCAAAAACTGAAGAGTCTTCTGGAAATTCTCGA 2719 chr5 ENST000002 GAATTTCCAGAAGACTCTTCAG 74520.1 INHA AATTCAAAAACCTCGGATGGAGGTTACTCTTCTCGA 2720 chr2 ENST000002 GAAGAGTAACCTCCATCCGAGG 43786.2 INHA AATTCAAAAAGCAGCACTGTGCTTGTATCTACTCGA 2721 chr2 ENST000002 GTAGATACAAGCACAGTGCTGC 43786.2 INHA AATTCAAAAATGGAGGTTACTCTTTCAAGTACTCGA 2722 chr2 ENST000002 GTACTTGAAAGAGTAACCTCCA 43786.2 INHBA AATTCAAAAAAGGCACTTTCCTACCCAATTACTCGA 2723 chr7 ENST000002 GTAATTGGGTAGGAAAGTGCCT 42208.4 INHBA AATTCAAAAAGAGAATGGTGTACCCTTTATTCTCGA 2724 chr7 ENST000002 GAATAAAGGGTACACCATTCTC 42208.4 INHBA AATTCAAAAAAGACGCTGCACTTCGAGATTTCTCGA 2725 chr7 ENST000002 GAAATCTCGAAGTGCAGCGTCT 42208.4 INHBB AATTCAAAAACAAATGGATGCGGTGACAAATCTCG 2726 chr2 ENST000002 AGATTTGTCACCGCATCCATTTG 95228.3 INHBB AATTCAAAAAGCTGGAACGACTGGATCATAGCTCG 2727 chr2 ENST000002 AGCTATGATCCAGTCGTTCCAGC 95228.3 INHBB AATTCAAAAATGATGAGTACAACATCGTCAACTCGA 2728 chr2 ENST000002 GTTGACGATGTTGTACTCATCA 95228.3 INHBC AATTCAAAAATCAACCAGACTCGTCTTGATTCTCGA 2729 chr12 ENST000003 GAATCAAGACGAGTCTGGTTGA 09668.2 INHBC AATTCAAAAACAAGACTGACATACCTGACATCTCGA 2730 chr12 ENST000003 GATGTCAGGTATGTCAGTCTTG 09668.2 INHBC AATTCAAAAACAGGCCAGTCTCATGTTCTTTCTCGA 2731 chr12 ENST000003 GAAAGAACATGAGACTGGCCTG 09668.2 INHBE AATTCAAAAACTCCTCTACCTGGATCATAATCTCGA 2732 chr12 ENST000002 GATTATGATCCAGGTAGAGGAG 66646.2 INHBE AATTCAAAAAACCTGGGCTGGCATACCTTAACTCGA 2733 chr12 ENST000002 GTTAAGGTATGCCAGCCCAGGT 66646.2 INHBE AATTCAAAAAGCAGCCCTTCCTAGAGCTTAACTCGA 2734 chr12 ENST000002 GTTAAGCTCTAGGAAGGGCTGC 66646.2 ITGA4 AATTCAAAAACCAACGCTTCAGTGATCAATCCTCGA 2735 chr2 ENST000003 GGATTGATCACTGAAGCGTTGG 97033.6 ITGA4 AATTCAAAAATGTAGAACACATCAAGCATTTCTCGA 2736 chr2 ENST000003 GAAATGCTTGATGTGTTCTACA 97033.6 ITGA4 AATTCAAAAACATGATCTTGTGACATATTATCTCGA 2737 chr2 ENST000003 GATAATATGTCACAAGATCATG 97033.6 ITGAV AATTCAAAAATTGAAGTGTACCCTAGCATTTCTCGA 2738 chr2 ENST000002 GAAATGCTAGGGTACACTTCAA 61023.7 ITGAV AATTCAAAAACACTCCAAGAACATGACTATTCTCGA 2739 chr2 ENST000002 GAATAGTCATGTTCTTGGAGTG 61023.7 ITGAV AATTCAAAAAGTGAGGTCGAAACAGGATAAACTCG 2740 chr2 ENST000002 AGTTTATCCTGTTTCGACCTCAC 61023.7 ITGB1 AATTCAAAAATTTGTAGGAAGAGGGATAATACTCG 2741 chr10 ENST000003 AGTATTATCCCTCTTCCTACAAA 02278.7 ITGB1 AATTCAAAAAGCCTTGCATTACTGCTGATATCTCGA 2742 chr10 ENST000003 GATATCAGCAGTAATGCAAGGC 02278.7 ITGB1 AATTCAAAAAGCCTTGCATTACTGCTGATATCTCGA 2743 chr10 ENST000003 GATATCAGCAGTAATGCAAGGC 02278.7 ITGB3 AATTCAAAAAGTCGTCAGATTCCAGTACTATCTCGA 2744 chr17 ENST000005 GATAGTACTGGAATCTGACGAC 59488.5 ITGB3 AATTCAAAAAGTCGTCAGATTCCAGTACTATCTCGA 2745 chr17 ENST000005 GATAGTACTGGAATCTGACGAC 59488.5 ITGB3 AATTCAAAAACCACGTCTACCTTCACCAATACTCGA 2746 chr17 ENST000005 GTATTGGTGAAGGTAGACGTGG 59488.5 KIT AATTCAAAAAACTTCATCTAACGAGATTAAACTCGA 2747 chr4 ENST000002 GTTTAATCTCGTTAGATGAAGT 88135.5 KIT AATTCAAAAAGCGACGAGATTAGGCTGTTATCTCGA 2748 chr4 ENST000002 GATAACAGCCTAATCTCGTCGC 88135.5 KIT AATTCAAAAAACGAGTTGGCCCTAGACTTAGCTCGA 2749 chr4 ENST000002 GCTAAGTCTAGGGCCAACTCGT 88135.5 KITLG AATTCAAAAAGCAGGAATCGTGTGACTAATACTCG 2750 chr12 ENST000002 AGTATTAGTCACACGATTCCTGC 28280.9 KITLG AATTCAAAAAGCAGGAATCGTGTGACTAATACTCG 2751 chr12 ENST000002 AGTATTAGTCACACGATTCCTGC 28280.9 KITLG AATTCAAAAACCTATTTAATCCTCTCGTCAACTCGA 2752 chr12 ENST000002 GTTGACGAGAGGATTAAATAGG 28280.9 KLHL20 AATTCAAAAAGCCAATACATGGAGGTTATATCTCGA 2753 chr1 ENST000002 GATATAACCTCCATGTATTGGC 09884.4 KLHL20 AATTCAAAAAGCCGCAAGAACGACCACTAATCTCG 2754 chr1 ENST000002 AGATTAGTGGTCGTTCTTGCGGC 09884.4 KLHL20 AATTCAAAAACACATTGTGAATCCCATATTTCTCGA 2755 chr1 ENST000002 GAAATATGGGATTCACAATGTG 09884.4 LEFTY1 AATTCAAAAAACAAGTTACCTCACCTAATTTCTCGA 2756 chr1 ENST000002 GAAATTAGGTGAGGTAACTTGT 72134.5 LEFTY1 AATTCAAAAAAGCCCAATGTGTCATTGTTTACTCGA 2757 chr1 ENST000002 GTAAACAATGACACATTGGGCT 72134.5 LEFTY1 AATTCAAAAATCTCTAGTGAGCCCTGAATTTCTCGA 2758 chr1 ENST000002 GAAATTCAGGGCTCACTAGAGA 72134.5 LEFTY2 AATTCAAAAAAGTTACTCCATCCCAATTTAGCTCGA 2759 chr1 ENST000003 GCTAAATTGGGATGGAGTAACT 66820.9 LEFTY2 AATTCAAAAACTAAGCACTTACGTGAGTAAACTCGA 2760 chr1 ENST000003 GTTTACTCACGTAAGTGCTTAG 66820.9 LEFTY2 AATTCAAAAATAGGCGCCTGGTGTATCCATTCTCGA 2761 chr1 ENST000003 GAATGGATACACCAGGCGCCTA 66820.9 LIF AATTCAAAAAGCAGTGCCAATGCCCTCTTTACTCGA 2762 chr22 ENST000002 GTAAAGAGGGCATTGGCACTGC 49075.3 LIF AATTCAAAAAACCGCATAGTCGTGTACCTTGCTCGA 2763 chr22 ENST000002 GCAAGGTACACGACTATGCGGT 49075.3 LIF AATTCAAAAACAACAACCTGGACAAGCTATGCTCG 2764 chr22 ENST000002 AGCATAGCTTGTCCAGGTTGTTG 49075.3 LIFR AATTCAAAAATGACTTGCGACTACGTCATTACTCGA 2765 chr5 ENST000002 GTAATGACGTAGTCGCAAGTCA 63409.8 LIFR AATTCAAAAAACTTCTGCAGATTCGATATTACTCGA 2766 chr5 ENST000002 GTAATATCGAATCTGCAGAAGT 63409.8 LIFR AATTCAAAAAGTAGGCTCAGACATAACATTTCTCGA 2767 chr5 ENST000002 GAAATGTTATGTCTGAGCCTAC 63409.8 LTA AATTCAAAAAGCCCTAGTACTGTCTTCTTTGCTCGA 2768 chr6 ENST000004 GCAAAGAAGACAGTACTAGGGC 18386.2 LTA AATTCAAAAAGATCAAGTCACCGGAGCTTTCCTCGA 2769 chr6 ENST000004 GGAAAGCTCCGGTGACTTGATC 18386.2 LTA AATTCAAAAAGCTCCCAGAAGATGGTGTATCCTCGA 2770 chr6 ENST000004 GGATACACCATCTTCTGGGAGC 18386.2 LTB AATTCAAAAAGCGAGAGGGAAGACCTTCTTTCTCGA 2771 chr6 ENST000004 GAAAGAAGGTCTTCCCTCTCGC 29299.2 LTB AATTCAAAAACGAGAGGGTGTACGTCAACATCTCG 2772 chr6 ENST000004 AGATGTTGACGTACACCCTCTCG 29299.2 LTB AATTCAAAAAGACGAAGGAACAGGCGTTTCTCTCG 2773 chr6 ENST000004 AGAGAAACGCCTGTTCCTTCGTC 29299.2 LTBP1 AATTCAAAAAGATGACCTGTGTCGATGTAAACTCGA 2774 chr2 ENST000004 GTTTACATCGACACAGGTCATC 07925.5 LTBP1 AATTCAAAAAGGTGGAACAGTGCTGTTATTTCTCGA 2775 chr2 ENST000004 GAAATAACAGCACTGTTCCACC 07925.5 LTBP1 AATTCAAAAACCGTTGAATACCGCCTTGAATCTCGA 2776 chr2 ENST000004 GATTCAAGGCGGTATTCAACGG 07925.5 LTBP3 AATTCAAAAAGCATCCTCAATGGATGTGAAACTCGA 2777 chr11 ENST000003 GTTTCACATCCATTGAGGATGC 22147.8 LTBP3 AATTCAAAAATGTTGTTCGGGTCGGAGATTTCTCGA 2778 chr11 ENST000003 GAAATCTCCGACCCGAACAACA 22147.8 LTBP3 AATTCAAAAAAGCGCTTCAAGGTGGTCTTTGCTCGA 2779 chr11 ENST000003 GCAAAGACCACCTTGAAGCGCT 22147.8 LTBP4 AATTCAAAAAGCTTCGACATGCCAGACTTTGCTCGA 2780 chr19 ENST000003 GCAAAGTCTGGCATGTCGAAGC 08370.11 LTBP4 AATTCAAAAATGAAACACTACAGGGTGTATGCTCG 2781 chr19 ENST000003 AGCATACACCCTGTAGTGTTTCA 08370.11 LTBP4 AATTCAAAAACAACCGGCTTTGAAAGAGTTACTCGA 2782 chr19 ENST000003 GTAACTCTTTCAAAGCCGGTTG 08370.11 MAF AATTCAAAAATCAGTGGGATACGCCACATTTCTCGA 2783 chr16 ENST000003 GAAATGTGGCGTATCCCACTGA 26043.4 MAF AATTCAAAAATTTATGGTGTGTGCAAGTAAACTCGA 2784 chr16 ENST000003 GTTTACTTGCACACACCATAAA 26043.4 MAF AATTCAAAAAGTTAGAGAAGAAGGCTATTAACTCG 2785 chr16 ENST000003 AGTTAATAGCCTTCTTCTCTAAC 26043.4

MAF AATTCAAAAATGTTAATGACTTCGATCTGATCTCGA 2786 chr16 ENST000003 GATCAGATCGAAGTCATTAACA 26043.4 MIF AATTCAAAAACTACATCAACTATTACGACATCTCGA 2787 chr22 ENST000002 GATGTCGTAATAGTTGATGTAG 15754.7 MIF AATTCAAAAACTACATCAACTATTACGACATCTCGA 2788 chr22 ENST000002 GATGTCGTAATAGTTGATGTAG 15754.7 MIF AATTCAAAAAGACAGGGTCTACATCAACTATCTCGA 2789 chr22 ENST000002 GATAGTTGATGTAGACCCTGTC 15754.7 MINO AATTCAAAAAGCCAAGCTGCACAATTTAATACTCGA 2790 chr1 ENST000006 S1- GTATTAAATTGTGCAGCTTGGC 02662.1 MINO AATTCAAAAAGCTGGCACTGTTCCCAGATAACTCGA 2791 chr1 ENST000006 S1- GTTATCTGGGAACAGTGCCAGC 02662.1 MINO AATTCAAAAAAGAAAGACCACTGGCAGAAACCTCG 2792 chr1 ENST000006 S1- AGGTTTCTGCCAGTGGTCTTTCT 02662.1 MSTN AATTCAAAAAAGGCCCAACTATGGATATATTCTCGA 2793 chr2 ENST000002 GAATATATCCATAGTTGGGCCT 60950.4 MSTN AATTCAAAAAGAGCTAGAAGGAGATCAAATTCTCG 2794 chr2 ENST000002 AGAATTTGATCTCCTTCTAGCTC 60950.4 MSTN AATTCAAAAAGTATGCTTTAAAGTCTATTTCCTCGA 2795 chr2 ENST000002 GGAAATAGACTTTAAAGCATAC 60950.4 NAMPT AATTCAAAAAAGCGATAGCTATGACATTTATCTCGA 2796 chr7 ENST000002 GATAAATGTCATAGCTATCGCT 22553.7 NAMPT AATTCAAAAAGTGAAGATCTAAGACATTTAACTCGA 2797 chr7 ENST000002 GTTAAATGTCTTAGATCTTCAC 22553.7 NAMPT AATTCAAAAATACAAGGTTACTCACTATAAACTCGA 2798 chr7 ENST000002 GTTTATAGTGAGTAACCTTGTA 22553.7 NBL1 AATTCAAAAAGCCAAGCTGCACAATTTAATACTCGA 2799 chr1 ENST000003 GTATTAAATTGTGCAGCTTGGC 75136.7 NBL1 AATTCAAAAAGCTGGCACTGTTCCCAGATAACTCGA 2800 chr1 ENST000003 GTTATCTGGGAACAGTGCCAGC 75136.7 NBL1 AATTCAAAAAAGAAAGACCACTGGCAGAAACCTCG 2801 chr1 ENST000003 AGGTTTCTGCCAGTGGTCTTTCT 75136.7 NDP AATTCAAAAACTGCTAAAGGTTACCGATTTCCTCGA 2802 chrX ENST000003 GGAAATCGGTAACCTTTAGCAG 78062.5 NDP AATTCAAAAACTCTGCATATTCTAGTAATAACTCGA 2803 chrX ENST000003 GTTATTACTAGAATATGCAGAG 78062.5 NDP AATTCAAAAAACGGACAGCTCATTCATAATGCTCGA 2804 chrX ENST000003 GCATTATGAATGAGCTGTCCGT 78062.5 NLRP7 AATTCAAAAACCGTTCAAGGAAATTTCTATTCTCGA 2805 chr19 ENST000003 GAATAGAAATTTCCTTGAACGG 28092.9 NLRP7 AATTCAAAAACGGGTCTCTAAGATGTCTTATCTCGA 2806 chr19 ENST000003 GATAAGACATCTTAGAGACCCG 28092.9 NLRP7 AATTCAAAAAACCTGCTCAGAAATCATAAATCTCGA 2807 chr19 ENST000003 GATTTATGATTTCTGAGCAGGT 28092.9 NODAL AATTCAAAAAGTGCTCCTAGATCACCATAAACTCGA 2808 chr10 ENST000002 GTTTATGGTGATCTAGGAGCAC 87139.7 NODAL AATTCAAAAACACCTATAGCTTTCATGTATTCTCGA 2809 chr10 ENST000002 GAATACATGAAAGCTATAGGTG 87139.7 NODAL AATTCAAAAAGCATGCTGTATGTGGATAATGCTCGA 2810 chr10 ENST000002 GCATTATCCACATACAGCATGC 87139.7 NOG AATTCAAAAAAGGTCAGTATTATACGTTAAACTCGA 2811 chr17 ENST000003 GTTTAACGTATAATACTGACCT 32822.4 NOG AATTCAAAAAATTCTGGTTGTTGCTAATAATCTCGA 2812 chr17 ENST000003 GATTATTAGCAACAACCAGAAT 32822.4 NOG AATTCAAAAATGCGGAGGAAGTTACAGATGTCTCG 2813 Chr17 ENST000003 AGACATCTGTAACTTCCTCCGCA 32822.4 NRG1 AATTCAAAAAGATATCACAGAGGCCTATAACCTCG 2814 Chr8 ENST000002 AGGTTATAGGCCTCTGTGATATC 87842.7 NRG1 AATTCAAAAAGGCTGATTCTGGAGAGTATATCTCGA 2815 chr8 ENST000002 GATATACTCTCCAGAATCAGCC 87842.7 NRG1 AATTCAAAAAGACAGTGCCTCTGCCAATATCCTCGA 2816 chr8 ENST000002 GGATATTGGCAGAGGCACTGTC 87842.7 NRP1 AATTCAAAAATATACTAGAATCACCGCATTTCTCGA 2817 chr10 ENST000002 GAAATGCGGTGATTCTAGTATA 65371.8 NRP1 AATTCAAAAACAGCCTTGAATGCACTTATATCTCGA 2818 chr10 ENST000002 GATATAAGTGCATTCAAGGCTG 65371.8 NRP1 AATTCAAAAACAGCCTTGAATGCACTTATATCTCGA 2819 chr10 ENST000002 GATATAAGTGCATTCAAGGCTG 65371.8 NRP2 AATTCAAAAACGACTGCAAGTATGACTTTATCTCGA 2820 chr2 ENST000003 GATAAAGTCATACTTGCAGTCG 57785.9 NRP2 AATTCAAAAACCGGATTGCTAATGAACAGATCTCGA 2821 chr2 ENST000003 GATCTGTTCATTAGCAATCCGG 57785.9 NRP2 AATTCAAAAACCTCAACTTCAACCCTCACTTCTCGA 2822 chr2 ENST000003 GAAGTGAGGGTTGAAGTTGAGG 57785.9 OSM AATTCAAAAAACTTCCTCCTTTCCGTGTTTCCTCGAG 2823 chr22 ENST000002 GAAACACGGAAAGGAGGAAGT 15781.2 OSM AATTCAAAAAGGACCGACTTTCCATTGATTCCTCGA 2824 chr22 ENST000002 GGAATCAATGGAAAGTCGGTCC 15781.2 OSM AATTCAAAAATGGTCCTTGCACTCCTGTTTCCTCGA 2825 chr22 ENST000002 GGAAACAGGAGTGCAAGGACCA 15781.2 OSMR AATTCAAAAATAACCTGACTCATCGAGTTTACTCGA 2826 chr5 ENST000002 GTAAACTCGATGAGTCAGGTTA 74276.7 OSMR AATTCAAAAAAGGAGAACCCTCACCTAATAACTCG 2827 chr5 ENST000002 AGTTATTAGGTGAGGGTTCTCCT 74276.7 OSMR AATTCAAAAAGCACTCCATAAGGAATAATTTCTCGA 2828 chr5 ENST000002 GAAATTATTCCTTATGGAGTGC 74276.7 PARK7 AATTCAAAAAGTAGCCGTGATGTGGTCATTTCTCGA 2829 chr1 ENST000003 GAAATGACCACATCACGGCTAC 38639.9 PARK7 AATTCAAAAAGCAATTGTTGAAGCCCTGAATCTCGA 2830 chr1 ENST000003 GATTCAGGGCTTCAACAATTGC 38639.9 PARK7 AATTCAAAAAACTCTGAGAATCGTGTGGAAACTCG 2831 chr1 ENST000003 AGTTTCCACACGATTCTCAGAGT 38639.9 PDPN AATTCAAAAAGCCTCTGGTATGAGAAATAAACTCG 2832 chr1 ENST000002 AGTTTATTTCTCATACCAGAGGC 94489.10 PDPN AATTCAAAAAAGTCCACGCGCAAGAACAAAGCTCG 2833 chr1 ENST000002 AGCTTTGTTCTTGCGCGTGGACT 94489.10 PDPN AATTCAAAAATGACCCTGGTTGGAATCATAGCTCGA 2834 chr1 ENST000002 GCTATGATTCCAACCAGGGTCA 94489.10 PF4 AATTCAAAAAACGCTGAAGAATGGAAGGAAACTCG 2835 chr4 ENST000002 AGTTTCCTTCCATTCTTCAGCGT 96029.3 PF4 AATTCAAAAACCAACTGATAGCCACGCTGAACTCG 2836 chr4 ENST000002 AGTTCAGCGTGGCTATCAGTTGG 96029.3 PF4 AATTCAAAAACACGCTGAAGAATGGAAGGAACTCG 2837 chr4 ENST000002 AGTTCCTTCCATTCTTCAGCGTG 96029.3 PF4V1 AATTCAAAAAGTTGTGGTATAGTCAATCTATCTCGA 2838 chr4 ENST000002 GATAGATTGACTATACCACAAC 26524.3 PF4V1 AATTCAAAAAAGCTGCCTAAGTGTGCACTTTCTCGA 2839 chr4 ENST000002 GAAAGTGCACACTTAGGCAGCT 26524.3 PF4V1 AATTCAAAAACTGACACATCACAATTTCATACTCGA 2840 chr4 ENST000002 GTATGAAATTGTGATGTGTCAG 26524.3 PGLYRP1 AATTCAAAAAGTGCCCACTCAGGTCACTTATCTCGA 2841 chr19 ENST000000 GATAAGTGACCTGAGTGGGCAC 08938.4 PGLYRP1 AATTCAAAAACTTACGCTATGTGGTGGTATCCTCGA 2842 chr19 ENST000000 GGATACCACCACATAGCGTAAG 08938.4 PGLYRP1 AATTCAAAAACATCAGCTTCATGGGCAACTACTCGA 2843 chr19 ENST000000 GTAGTTGCCCATGAAGCTGATG 08938.4 PLP2 AATTCAAAAACCTGTCGGTGATTGAGATGATCTCGA 2844 chrX ENST000003 GATCATCTCAATCACCGACAGG 76327.5 PLP2 AATTCAAAAACCTGTCGGTGATTGAGATGATCTCGA 2845 chrX ENST000003 GATCATCTCAATCACCGACAGG 76327.5 PLP2 AATTCAAAAACGAAAGGGAATCCTCCTGTTTCTCGA 2846 chrX ENST000003 GAAACAGGAGGATTCCCTTTCG 76327.5 PPBP AATTCAAAAAAGGTGATGAATCTGCTGATTACTCGA 2847 chr4 ENST000002 GTAATCAGCAGATTCATCACCT 96028.3 PPBP AATTCAAAAATGTTTCTGCCAAACTTCTTTACTCGA 2848 chr4 ENST000002 GTAAAGAAGTTTGGCAGAAACA 96028.3 PPBP AATTCAAAAACTCCCAGGAAGGGTAGAATTTCTCGA 2849 chr4 ENST000002 GAAATTCTACCCTTCCTGGGAG 96028.3 PXDN AATTCAAAAAAGATTGCGACTGGACTCAAACCTCG 2850 chr2 ENST000002 AGGTTTGAGTCCAGTCGCAATCT 52804.8 PXDN AATTCAAAAAGTTCCTGACGTCAGTCGAAATCTCGA 2851 chr2 ENST000002 GATTTCGACTGACGTCAGGAAC 52804.8 PXDN AATTCAAAAAGAAGGATTCTTGACCATCAATCTCGA 2852 chr2 ENST000002 GATTGATGGTCAAGAATCCTTC 52804.8 RORC AATTCAAAAACACCTCACAAATTGAAGTGATCTCGA 2853 chr1 ENST000003 GATCACTTCAATTTGTGAGGTG 18247.6 RORC AATTCAAAAAGCCCTCATATTCCAACAACTTCTCGA 2854 chr1 ENST000003 GAAGTTGTTGGAATATGAGGGC 18247.6 RORC AATTCAAAAAGCTTCTCAAAGCAGGAGCAATCTCG 2855 chr1 ENST000003 AGATTGCTCCTGCTTTGAGAAGC 18247.6 RORC AATTCAAAAACGAGGATGAGATTGCCCTCTACTCGA 2856 chr1 ENST000003 GTAGAGGGCAATCTCATCCTCG 18247.6 SCG2 AATTCAAAAAACGACAAGGATCAAGAATTAGCTCG 2857 chr2 ENST000003 AGCTAATTCTTGATCCTTGTCGT 05409.2 SCG2 AATTCAAAAACCTGTCTCTTATCCCTTTAATCTCGAG 2858 chr2 ENST000003 ATTAAAGGGATAAGAGACAGG 05409.2 SCG2 AATTCAAAAAGAAAGCAGCCCAGATTATAATCTCG 2859 chr2 ENST000003 AGATTATAATCTGGGCTGCTTTC 05409.2 SCGB3A1 AATTCAAAAATCATAGAGGGCTCCCAGAAGTCTCG 2860 chr5 ENST000002 AGACTTCTGGGAGCCCTCTATGA 92641.3 SCGB3A1 AATTCAAAAACCCGTGAACCACCTCATAGAGCTCGA 261 chr5 ENST000002 GCTCTATGAGGTGGTTCACGGG 92641.3 SCGB3A1 AATTCAAAAAGACTGGAGCATCTACACCTGACTCGA 2862 chr5 ENST000002 GTCAGGTGTAGATGCTCCAGTC 92641.3 SECTM1 AATTCAAAAACACCAGAGAAATAACAGACAACTCG 2863 chr17 ENST000002 AGTTGTCTGTTATTTCTCTGGTG 69389.7 SECTM1 AATTCAAAAACCATGACTCGAATATCTGAAACTCGA 2864 chr17 ENST000002 GTTTCAGATATTCGAGTCATGG 69389.7 SECTM1 AATTCAAAAACCATGACTCGAATATCTGAAACTCGA 2865 chr17 ENST000002 GTTTCAGATATTCGAGTCATGG 69389.7 SLURP1 AATTCAAAAAGTGCTTCCTGCAGGACCATTACTCGA 2866 chr8 ENST000002 GTAATGGTCCTGCAGGAAGCAC 46515.1 SLURP1 AATTCAAAAAAGACCTCTGCAACTCGGAACTCTCGA 2867 chr8 ENST000002 GAGTTCCGAGTTGCAGAGGTCT 46515.1 SLURP1 AATTCAAAAACTCAAGTGCTACACCTGCAAGCTCGA 2868 chr8 ENST000002 GCTTGCAGGTGTAGCACTTGAG 46515.1 SOSTDC1 AATTCAAAAAGATGCCACAGAAATCCTTTATCTCGA 2869 chr7 ENST000003 GATAAAGGATTTCTGTGGCATC 07068.4

SOSTDC1 AATTCAAAAAGGAACTGCGTTCCACCAAATACTCGA 2870 chr7 ENST000003 GTATTTGGTGGAACGCAGTTCC 07068.4 SOSTDC1 AATTCAAAAATGAATCTTCACAGTAACATTTCTCGA 2871 chr7 ENST000003 GAAATGTTACTGTGAAGATTCA 07068.4 SP100 AATTCAAAAAGAAGTGAGCCTGTGATCAATACTCG 2872 chr2 ENST000003 AGTATTGATCACAGGCTCACTTC 40126.8 SP100 AATTCAAAAATATACGCTGCGGTGGATATACCTCGA 2873 chr2 ENST000003 GGTATATCCACCGCAGCGTATA 40126.8 SP100 AATTCAAAAATCGTGATCTCATCACAAATAACTCGA 2874 chr2 ENST000003 GTTATTTGTGATGAGATCACGA 40126.8 SPI1 AATTCAAAAAGCCCTATGACACGGATCTATACTCGA 2875 chr11 ENST000003 GTATAGATCCGTGTCATAGGGC 78538.7 SPI1 AATTCAAAAAAGAGCTTCGCCGAGAACAACTCTCG 2876 chr11 ENST000003 AGAGTTGTTCTCGGCGAAGCTCT 78538.7 SPI1 AATTCAAAAACGGATCTATACCAACGCCAAACTCG 2877 chr11 ENST000003 AGTTTGGCGTTGGTATAGATCCG 78538.7 SPI1 AATTCAAAAACCGTATGTAAATCAGATCTCCCTCGA 2878 chr11 ENST000003 GGGAGATCTGATTTACATACGG 78538.7 SPP1 AATTCAAAAACCACAAGCAGTCCAGATTATACTCGA 2879 chr4 ENST000002 GTATAATCTGGACTGCTTGTGG 37623.11 SPP1 AATTCAAAAACCGAGGTGATAGTGTGGTTTACTCGA 2880 chr4 ENST000002 GTAAACCACACTATCACCTCGG 37623.11 SPP1 AATTCAAAAACTTCAGGGTTATGTCTATGTTCTCGA 2881 chr4 ENST000002 GAACATAGACATAACCCTGAAG 37623.11 TBX21 AATTCAAAAAGCCCTAACTACAGTCGTTTACCTCGA 2882 ch17 ENST000001 GGTAAACGACTGTAGTTAGGGC 77694.1 TBX21 AATTCAAAAACCTGTTGTGGTCCAAGTTTAACTCGA 2883 ch17 ENST000001 GTTAAACTTGGACCACAACAGG 77694.1 TBX21 AATTCAAAAACGCTTCCAACACGCATATCTTCTCGA 2884 ch17 ENST000001 GAAGATATGCGTGTTGGAAGCG 77694.1 TBX21 AATTCAAAAAACAATGTGACCCAGATGATTGCTCGA 2885 ch17 ENST000001 GCAATCATCTGGGTCACATTGT 77694.1 TCAP AATTCAAAAACTTTGTAGTTTGCCCAGAGTTCTCGA 2886 chr17 ENST000003 GAACTCTGGGCAAACTACAAAG 09889.2 TCAP ATTCAAAAAGGCCATGGCTGCTTTGTAGTTCTCGA 2887 chr17 ENST000003 GAACTACAAAGCAGCCATGGCC 09889.2 TCAP AATTCAAAAAGGTGGCTGAGATCACAAAGCACTCG 2888 chr17 ENST000003 AGTGCTTTGTGATCTCAGCCACC 09889.2 TGFB1 AATTCAAAAAACTGCGGATCTCTGTGTCATTCTCGA 2889 chr19 ENST000002 GAATGACACAGAGATCCGCAGT 21930.5 TGFB1 AATTCAAAAACCACAACGAAATCTATGACAACTCG 2890 chr19 ENST000002 AGTTGTCATAGATTTCGTTGTGG 21930.5 TGFB1 AATTCAAAAACCACAACGAAATCTATGACAACTCG 2891 chr19 ENST000002 AGTTGTCATAGATTTCGTTGTGG 21930.5 TGFB2 AATTCAAAAAGCGGCCTATTGCTTTAGAAATCTCGA 2892 chr1 ENST000003 GATTTCTAAAGCAATAGGCCGC 66930.8 TGFB2 AATTCAAAAAGCTGGAGCATGCCCGTATTTACTCGA 2893 chr1 ENST000003 GTAAATACGGGCATGCTCCAGC 66930.8 TGFB2 AATTCAAAAATTGCTGCCTACGTCCACTTTACTCGA 2894 chr1 ENST000003 GTAAAGTGGACGTAGGCAGCAA 66930.8 TGFB3 AATTCAAAAACATTGCCAAACAGCGCTATATCTCGA 2895 chr14 ENST000002 GATATAGCGCTGTTTGGCAATG 38682.7 TGFB3 AATTCAAAAAGCTCTAGGGAATCTGGATTATCTCGA 2896 chr14 ENST000002 GATAATCCAGATTCCCTAGAGC 38682.7 TGFB3 AATTCAAAAACGGAATACTATGCCAAAGAAACTCG 2897 chr14 ENST000002 AGTTTCTTTGGCATAGTATTCCG 38682.7 TGFBR1 AATTCAAAAAGCCTTGAGAGTAATGGCTAAACTCG 2898 chr9 ENST000003 AGTTTAGCCATTACTCTCAAGGC 74994.8 TGFBR1 AATTCAAAAACTCATGTTGATGGTCTATATCCTCGA 2899 chr9 ENST000003 GGATATAGACCATCAACATGAG 74994.8 TGFBR1 AATTCAAAAAGAAGTTGCTGTTAAGATATTCCTCGA 2900 chr9 ENST000003 GGAATATCTTAACAGCAACTTC 74994.8 TGFBR2 AATTCAAAAACGTTCAGAAGTCGGTTAATAACTCGA 2901 chr3 ENST000002 GTTATTAACCGACTTCTGAACG 95754.9 TGFBR2 AATTCAAAAACTCTAGGCTTTATCGTGTTTACTCGA 2902 chr3 ENST000002 GTAAACACGATAAAGCCTAGAG 95754.9 TGFBR2 AATTCAAAAACTCAGGAAATGAGATTGATTTCTCGA 2903 chr3 ENST000002 GAAATCAATCTCATTTCCTGAG 95754.9 TGFBR3 AATTCAAAAAGGAGTTGGTAAAGGGTTAATACTCG 2904 chr1 ENST000002 AGTATTAACCCTTTACCAACTCC 12355.8 TGFBR3 AATTCAAAAATAATGGATTTCCGGGAGATATCTCGA 2905 chr1 ENST000002 GATATCTCCCGGAAATCCATTA 12355.8 TGFBR3 AATTCAAAAACACACCCAGGGCTAGTATAAACTCG 2906 chr1 ENST000002 AGTTTATACTAGCCCTGGGTGTG 12355.8 THBS1 AATTCAAAAAGTAGGTTATGATGAGTTTAATCTCGA 2907 chr15 ENST000002 GATTAAACTCATCATAACCTAC 60356.5 THBS1 AATTCAAAAACGTGACTGTAAGATTGTAAATCTCGA 2908 chr15 ENST000002 GATTTACAATCTTACAGTCACG 60356.5 THBS1 AATTCAAAAAGAGATCCCTAATCATCAAATTCTCGA 2909 chr15 ENST000002 GAATTTGATGATTAGGGATCTC 60356.5 THNSL2 AATTCAAAAAGAGCCGATCAAGACTGTGTTTCTCGA 2910 chr2 ENST000003 GAAACACAGTCTTGATCGGCTC 24166.6 THNSL2 AATTCAAAAAGCTGCCATTGAGAGTGTTCAACTCGA 2911 chr2 ENST000003 GTTGAACACTCTCAATGGCAGC 24166.6 THNSL2 AATTCAAAAAGCTGCCATTGAGAGTGTTCAACTCGA 2912 chr2 ENST000003 GTTGAACACTCTCAATGGCAGC 24166.6 THPO AATTCAAAAAGACCTCCGAGTCCTCAGTAAACTCGA 2913 chr3 ENST000002 GTTTACTGAGGACTCGGAGGTC 04615.11 THPO AATTCAAAAAAGCTAGCTCTTTGGTCTATTTCTCGA 2914 chr3 ENST000002 GAAATAGACCAAAGAGCTAGCT 04615.11 THPO AATTCAAAAACAACCTCCAGCCTGGATATTCCTCGA 2915 chr3 ENST000002 GGAATATCCAGGCTGGAGGTTG 04615.11 TIMP1 AATTCAAAAAGCACAGTGTTTCCCTGTTTATCTCGA 2916 chrX ENST000002 GATAAACAGGGAAACACTGTGC 18388.8 TIMP1 AATTCAAAAAGCACAGTGTTTCCCTGTTTATCTCGA 2917 chrX ENST000002 GATAAACAGGGAAACACTGTGC 18388.8 TIMP1 AATTCAAAAAACAGACGGCCTTCTGCAATTCCTCGA 2918 chrX ENST000002 GGAATTGCAGAAGGCCGTCTGT 18388.8 TNF AATTCAAAAAGAACCCAAGCTTAGAACTTTACTCGA 2919 chr6 ENST000004 GTAAAGTTCTAAGCTTGGGTTC 49264.2 TNF AATTCAAAAAGGAGCCAGCTCCCTCTATTTACTCGA 2920 chr6 ENST000004 GTAAATAGAGGGAGCTGGCTCC 49264.2 TNF AATTCAAAAATGGCGTGGAGCTGAGAGATAACTCG 2921 chr6 ENST000004 AGTTATCTCTCAGCTCCACGCCA 49264.2 TNFRSF4 AATTCAAAAAGCACGTGGTGTAACCTCAGAACTCG 2922 chr1 ENST000003 AGTTCTGAGGTTACACCACGTGC 79236.3 TNFRSF4 AATTCAAAAACAGCAATAGCTCGGACGCAATCTCG 2923 chr1 ENST000003 AGATTGCGTCCGAGCTATTGCTG 79236.3 TNFRSF4 AATTCAAAAAGACAGCTACAAGCCTGGAGTTCTCG 2924 chr1 ENST000003 AGAACTCCAGGCTTGTAGCTGTC 79236.3 TNFRSF4 AATTCAAAAAGCTTCTACAACGACGTGGTCACTCGA 2925 chr1 ENST000003 GTGACCACGTCGTTGTAGAAGC 79236.3 TNFRSF11 AATTCAAAAATGTTTACTTGCCCGGTTTAATCTCGA 2926 chr18 ENST000005 GATTAAACCGGGCAAGTAAACA 86569.2 TNFRSF11 AATTCAAAAATGTACCAGTGAGAAGCATTATCTCGA 2927 chr18 ENST000005 GATAATGCTTCTCACTGGTACA 86569.2 TNFRSF11 AATTCAAAAATGGGACGGTGCTGTAACAAATCTCG 2928 chr18 ENST000005 AGATTTGTTACAGCACCGTCCCA 86569.2 TNFRSF11 AATTCAAAAAGAAAGCACTCACAGCTAATTTCTCGA 2929 chr8 ENST000002 GAAATTAGCTGTGAGTGCTTTC 97350.8 TNFRSF11 AATTCAAAAAGATAAATGCTTGCTGCATAAACTCGA 2930 chr8 ENST000002 GTTTATGCAGCAAGCATTTATC 97350.8 TNFRSF11 AATTCAAAAACCAGTGTGTGTTCATTGTAAACTCGA 2931 chr8 ENST000002 GTTTACAATGAACACACACTGG 97350.8 TNFRSF1A AATTCAAAAAAGAACCAGTACCGGCATTATTCTCGA 2932 chr12 ENST000001 GAATAATGCCGGTACTGGTTCT 62749.6 TNFRSF1A AATTCAAAAAGGAGCTGTTGGTGGGAATATACTCG 2933 chr12 ENST000001 AGTATATTCCCACCAACAGCTCC 62749.6 TNFRSF1A AATTCAAAAACTTGAAGGAACTACTACTAAGCTCGA 2934 chr12 ENST000001 GCTTAGTAGTAGTTCCTTCAAG 62749.6 TNFRSF9 AATTCAAAAAGCTCCGTTTCTCTGTTGTTAACTCGA 2935 chr1 ENST000003 GTTAACAACAGAGAAACGGAGC 77507.7 TNFRSF9 AATTCAAAAACAAGAACACCATCCTACATAACTCG 2936 chr1 ENST000003 AGTTATGTAGGATGGTGTTCTTG 77507.7 TNFRSF9 AATTCAAAAACAGTCCCTGTCCTCCAAATAGCTCGA 2937 chr1 ENST000003 GCTATTTGGAGGACAGGGACTG 77507.7 TNFSF9 AATTCAAAAACAAGTTGGACCTTGATATTTACTCGA 2938 chr19 ENST000002 GTAAATATCAAGGTCCAACTTG 45817.4 TNFSF9 AATTCAAAAACTACTATGTCTTCTTTCAACTCTCGA 2939 chr19 ENST000002 GAGTTGAAAGAAGACATAGTAG 45817.4 TNFSF9 AATTCAAAAACCCTTCACCGAGGTCGGAATACTCGA 2940 chr19 ENST000002 GTATTCCGACCTCGGTGAAGGG 45817.4 TNFSF9 AATTCAAAAATGAGCTACAAAGAGGACACGACTCG 2941 chr19 ENST000002 AGTCGTGTCCTCTTTGTAGCTCA 45817.4 TNFSF10 AATTCAAAAAAGAAATAGTTGTTGGTCTAAACTCGA 2942 chr3 ENST000002 GTTTAGACCAACAACTATTTCT 41261.6 TNFSF10 AATTCAAAAAAGTTATCCTGACCCTATATTGCTCGA 2943 chr3 ENST000002 GCAATATAGGGTCAGGATAACT 41261.6 TNFSF10 AATTCAAAAAGACAAACAAATGGTCCAATATCTCG 2944 chr3 ENST000002 AGATATTGGACCATTTGTTTGTC 41261.6 TNFSF11 AATTCAAAAACTAATGGTGTACGTCACTAAACTCGA 2945 chr13 ENST000003 GTTTAGTGACGTACACCATTAG 98795.6 TNFSF11 AATTCAAAAACCGGATCAGGATGCAACATACCTCG 2946 chr13 ENST000003 AGGTATGTTGCATCCTGATCCGG 98795.6 TNFSF11 AATTCAAAAAGCAGTATATTTCTTCGTTCTTCTCGA 2947 chr13 ENST000003 GAAGAACGAAGAAATATACTGC 98795.6 TNFSF12 AATTCAAAAAGTATTCCCACTCTTATCTTACCTCGA 2948 chr17 ENST000002 GGTAAGATAAGAGTGGGAATAC 93825.10 TNFSF12 AATTCAAAAAGGGCATTGTGTTCACTGTACTCTCGA 2949 chr17 ENST000002 GAGTACAGTGAACACAATGCCC 93825.10 TNFSF12 AATTCAAAAACAGATGGAGGTTACACAACTTCTCGA 2950 chr17 ENST000002 GAAGTTGTGTAACCTCCATCTG 93825.10 TNFSF12- AATTCAAAAACCTCACCTACTTCGGACTCTTCTCGA 2951 chr17 ENST000002 GAAGAGTCCGAAGTAGGTGAGG 93826.4 TNFSF12- AATTCAAAAACTGTACTGTCAGGTGCACTTTCTCGA 2952 chr17 ENST000002 GAAAGTGCACCTGACAGTACAG 93826.4 TNFSF12- AATTCAAAAAGCGCAGGCAGATGGAGGTTACCTCG 2953 chr17 ENST000002

AGGTAACCTCCATCTGCCTGCGC 93826.4 TNFSF13 AATTCAAAAACAGTTGCCCTCTGGTTGAGTTCTCGA 2954 chr17 ENST000003 GAACTCAACCAGAGGGCAACTG 38784.8 TNFSF13 AATTCAAAAAATGGCTCTGCTGACCCAACAACTCGA 2955 chr17 ENST000003 GTTGTTGGGTCAGCAGAGCCAT 38784.8 TNFSF13 AATTCAAAAACCCAACAAACAGAGCTGCAGACTCG 2956 chr17 ENST000003 AGTCTGCAGCTCTGTTTGTTGGG 38784.8 TNFSF13B AATTCAAAAACCTGAAACACTACCCAATAATCTCGA 2957 chr13 ENST000003 GATTATTGGGTAGTGTTTCAGG 75887.8 TNFSF13B AATTCAAAAACTACGCCATGGGACATCTAATCTCGA 2958 chr13 ENST000003 GATTAGATGTCCCATGGCGTAG 75887.8 TNFSF13B AATTCAAAAAGTGACTTTGTTTCGATGTATTCTCGA 2959 chr13 ENST000003 GAATACATCGAAACAAAGTCAC 75887.8 TNFSF14 AATTCAAAAATCCTGGGAGCAGCTGATACAACTCG 2960 chr19 ENST000005 AGTTGTATCAGCTGCTCCCAGGA 99359.1 TNFSF14 AATTCAAAAAGACAGACCGACATCCCATTCACTCGA 2961 chr19 ENST000005 GTGAATGGGATGTCGGTCTGTC 99359.1 TNFSF14 AATTCAAAAAATGGGTCTGACACGTGGAGAACTCG 2962 chr19 ENST000005 AGTTCTCCACGTGTCAGACCCAT 99359.1 TNFSF15 AATTCAAAAAATTAAGACACTGATCACTAAACTCGA 2963 chr9 ENST000003 GTTTAGTGATCAGTGTCTTAAT 74045.4 TNFSF15 AATTCAAAAAGTCGGGAGACTACTTCATTTACTCGA 2964 chr9 ENST000003 GTAAATGAAGTAGTCTCCCGAC 74045.4 TNFSF15 AATTCAAAAAACTATAGGAGGAGAGCAAATACTCG 2965 chr9 ENST000003 AGTATTTGCTCTCCTCCTATAGT 74045.4 TNFSF18 AATTCAAAAACCTTCAGTTGGCTAATCTTTACTCGA 2966 chr1 ENST000004 GTAAAGATTAGCCAACTGAAGG 04377.3 TNFSF18 AATTCAAAAACTGAACCTCCTTGCGTGAATACTCGA 2967 chr1 ENST000004 GTATTCACGCAAGGAGGTTCAG 04377.3 TNFSF18 AATTCAAAAAATGATACAAACTCTAACAAACCTCG 2968 chr1 ENST000004 AGGTTTGTTAGAGTTTGTATCAT 04377.3 TNFSF4 AATTCAAAAAGTGGCCTCTCTGACTTACAAACTCGA 2969 chr1 ENST000002 GTTTGTAAGTCAGAGAGGCCAC 81834.3 TNFSF4 AATTCAAAAAGCAGAACAACTCAGTCATCATCTCGA 2970 chr1 ENST000002 GATGATGACTGAGTTGTTCTGC 81834.3 TNFSF4 AATTCAAAAAGCCAAGATTCGAGAGGAACAACTCG 2971 chr1 ENST000002 AGTTGTTCCTCTCGAATCTTGGC 81834.3 TNFSF8 AATTCAAAAAACTGTATGGTCTTGATCTATTCTCGA 2972 chr9 ENST000002 GAATAGATCAAGACCATACAGT 23795.2 TNFSF8 AATTCAAAAACAAACTACACAGGGTATTAAACTCG 2973 chr9 ENST000002 AGTTTAATACCCTGTGTAGTTTG 23795.2 TNFSF8 AATTCAAAAAGTGGATACATTCCAGTACATACTCGA 2974 chr9 ENST000002 GTATGTACTGGAATGTATCCAC 23795.2 TNFSF9 AATTCAAAAACAAGTTGGACCTTGATATTTACTCGA 2975 chr19 ENST000002 GTAAATATCAAGGTCCAACTTG 45817.4 TNFSF9 AATTCAAAAACTACTATGTCTTCTTTCAACTCTCGA 2976 chr19 ENST000002 GAGTTGAAAGAAGACATAGTAG 45817.4 TNFSF9 AATTCAAAAACCCTTCACCGAGGTCGGAATACTCGA 2977 chr19 ENST000002 GTATTCCGACCTCGGTGAAGGG 45817.4 TRIM16 AATTCAAAAAGCCGTTGTTCAGCGCAAATATCTCGA 2978 chr17 ENST000003 GATATTTGCGCTGAACAACGGC 36708.11 TRIM16 AATTCAAAAAGCCGTTGTTCAGCGCAAATATCTCGA 2979 chr17 ENST000003 GATATTTGCGCTGAACAACGGC 36708.11 TRIM16 AATTCAAAAACCGCATCAGGTGAACATCAAACTCG 2980 chr17 ENST000003 AGTTTGATGTTCACCTGATGCGG 36708.11 TSLP AATTCAAAAAACTCAATGATAGCACCTAAACCTCGA 2981 chr5 ENST000003 GGTTTAGGTGCTATCATTGAGT 44895.3 TSLP AATTCAAAAACGTCGCTTCAATCGACCTTTACTCGA 2982 chr5 ENST000003 GTAAAGGTCGATTGAAGCGACG 44895.3 TSLP AATTCAAAAACCATCTTTATTATGGTCATATCTCGA 2983 chr5 ENST000003 GATATGACCATAATAAAGATGG 44895.3 TWSG1 AATTCAAAAAGACTGTGTTGGTATGTGTAATCTCGA 2984 chr18 ENST000002 GATTACACATACCAACACAGTC 62120.9 TWSG1 AATTCAAAAAGCGCCTTATTCCAGTGACAAACTCGA 2985 chr18 ENST000002 GTTTGTCACTGGAATAAGGCGC 62120.9 TWSG1 AATTCAAAAAGAATCACTGAGCTGTAACAAACTCG 2986 chr18 ENST000002 AGTTTGTTACAGCTCAGTGATTC 62120.9 TXLNA AATTCAAAAAGCACATACTGTGTGGACAATACTCGA 2987 chr1 ENST000003 GTATTGTCCACACAGTATGTGC 73609.1 TXLNA AATTCAAAAATGCTGATGCAGACATTGAATACTCGA 2988 chr1 ENST000003 GTATTCAATGTCTGCATCAGCA 73609.1 TXLNA AATTCAAAAAAGCGAGGTATTCACCACATTCCTCGA 2989 chr1 ENST000003 GGAATGTGGTGAATACCTCGCT 73609.1 VASN AATTCAAAAAAGCTTGACTACGCCGACTTTGCTCGA 2990 chr16 ENST000003 GCAAAGTCGGCGTAGTCAAGCT 04735.3 VASN AATTCAAAAAAGCCAACAGGCTGCATGAAATCTCG 2991 chr16 ENST000003 AGATTTCATGCAGCCTGTTGGCT 04735.3 VASN AATTCAAAAAGAGATCCTTTCCCATTTATTCCTCGA 2992 chr16 ENST000003 GGAATAAATGGGAAAGGATCTC 04735.3 VEGFA AATTCAAAAACAAGATCCGCAGACGTGTAAACTCG 2993 chr6 ENST000004 AGTTTACACGTCTGCGGATCTTG 25836.6 VEGFA AATTCAAAAACAAGATCCGCAGACGTGTAAACTCG 2994 chr6 ENST000004 AGTTTACACGTCTGCGGATCTTG 25836.6 VEGFA AATTCAAAAAGCGCAAGAAATCCCGGTATAACTCG 2995 chr6 ENST000004 AGTTATACCGGGATTTCTTGCGC 25836.6 VSTM1 AATTCAAAAAATGAATATGCGGCACTGAAAGCTCG 2996 chr19 ENST000003 AGCTTTCAGTGCCGCATATTCAT 38372.6 VSTM1 AATTCAAAAACATTCCCAGAATGTGACATTTCTCGA 2997 chr19 ENST000003 GAAATGTCACATTCTGGGAATG 38372.6 VSTM1 AATTCAAAAAGAGTGACCTATGCTGAGCTAACTCGA 2998 chr19 ENST000003 GTTAGCTCAGCATAGGTCACTC 38372.6 WFIKKN1 AATTCAAAAATGCGCCCTGATCAGATGTATGCTCGA 2999 chr16 ENST000003 GCATACATCTGATCAGGGCGCA 19070.2 WFIKKN1 AATTCAAAAAGGACGTGCTCAAGGATGACAACTCG 3000 chr16 ENST000003 AGTTGTCATCCTTGAGCACGTCC 19070.2 WFIKKN1 AATTCAAAAAAGTGCTGCATCAACGTGTGTGCTCGA 3001 chr16 ENST000003 GCACACACGTTGATGCAGCACT 19070.2 WFIKKN2 AATTCAAAAATCAAGTTCTTGGGCACCAAGTCTCGA 3002 chr17 ENST000003 GACTTGGTGCCCAAGAACTTGA 11378.4 WFIKKN2 AATTCAAAAATACAACCGCTGCTATATGGACCTCGA 3003 chr17 ENST000003 GGTCCATATAGCAGCGGTTGTA 11378.4 WFIKKN2 AATTCAAAAACACCAGCTTGCTCAGATATTCCTCGA 3004 chr17 ENST000003 GGAATATCTGAGCAAGCTGGTG 11378.4 WNT1 AATTCAAAAACTGTCGAGAAACGGCGTTTATCTCGA 3005 chr12 ENST000002 GATAAACGCCGTTTCTCGACAG 93549.3 WNT1 AATTCAAAAAGACCTCGTCTACTTCGAGAAACTCGA 3006 chr12 ENST000002 GTTTCTCGAAGTAGACGAGGTC 93549.3 WNT1 AATTCAAAAAGCCACGAGTTTGGATGTTGTACTCGA 3007 chr12 ENST000002 GTACAACATCCAAACTCGTGGC 93549.3 WNT2 AATTCAAAAACCACAAATGGTCCCAATTAAGCTCGA 3008 chr7 ENST000002 GCTTAATTGGGACCATTTGTGG 65441.7 WNT2 AATTCAAAAATCGGGAATCTGCCTTTGTTTACTCGA 3009 chr7 ENST000002 GTAAACAAAGGCAGATTCCCGA 65441.7 WNT2 AATTCAAAAATTGACTATGGGATCAAATTTGCTCGA 3010 chr7 ENST000002 GCAAATTTGATCCCATAGTCAA 65441.7 WNT5A AATTCAAAAACTCCCAGGACCCGCTTATTTACTCGA 3011 chr3 ENST000002 GTAAATAAGCGGGTCCTGGGAG 64634.8 WNT5A AATTCAAAAACAAAGAATGCCAGTATCAATTCTCGA 3012 chr3 ENST000002 GAATTGATACTGGCATTCTTTG 64634.8 WNT5A AATTCAAAAACCTGTTCAGATGTCAGAAGTACTCGA 3013 chr3 ENST000002 GTACTTCTGACATCTGAACAGG 64634.8 WNT7A AATTCAAAAACATAGGAGAAGGCTCACAAATCTCG 3014 chr3 ENST000002 AGATTTGTGAGCCTTCTCCTATG 85018.4 WNT7A AATTCAAAAAGGCGCAAGCATCATCTGTAACCTCGA 3015 chr3 ENST000002 GGTTACAGATGATGCTTGCGCC 85018.4 WNT7A AATTCAAAAATCTTCGGGAAGGAGCTCAAAGCTCG 3016 chr3 ENST000002 AGCTTTGAGCTCCTTCCCGAAGA 85018.4 XCL1 AATTCAAAAAGCTGTGACAATGGCAACAATTCTCGA 3017 chr1 ENST000003 GAATTGTTGCCATTGTCACAGC 67818.3 XCL1 AATTCAAAAATTCAACTTGTCTCTATAATAGCTCGA 3018 chr1 ENST000003 GCTATTATAGAGACAAGTTGAA 67818.3 XCL1 AATTCAAAAAAGATTCTGGCTAGTGTCTATCCTCGA 3019 chr1 ENST000003 GGATAGACACTAGCCAGAATCT 67818.3 XCL2 AATTCAAAAAACTGCCAGTTAGCAGAATCAACTCG 3020 chr1 ENST000003 AGTTGATTCTGCTAACTGGCAGT 67819.2 XCL2 AATTCAAAAAGTAGGGAGTGAAGTCTCACATCTCG 3021 chr1 ENST000003 AGATGTGAGACTTCACTCCCTAC 67819.2 XCL2 AATTCAAAAAGAAATCCAACACCAGAAATAACTCG 3022 chr1 ENST000003 AGTTATTTCTGGTGTTGGATTTC 67819.2 ZFP36 AATTCAAAAAGATCCGACCCTGATGAATATGCTCGA 3023 chr19 ENST000005 GCATATTCATCAGGGTCGGATC 97629.1 ZFP36 AATTCAAAAAATCTGTCTCCTAGAATCTTATCTCGA 3024 chr19 ENST000005 GATAAGATTCTAGGAGACAGAT 97629.1 ZFP36 AATTCAAAAACCCTTTATTTATGACGACTTTCTCGA 3025 chr19 ENST000005 GAAAGTCGTCATAAATAAAGGG 97629.1

Example 16

Method of Making and Testing Cells Deficient in Specific Cytokine Expression Using Protein Expression Blockers (PEBL)--CAR19-GM-CSF PEBL

[0397] Inject tumor in SCID-Beige mice (3e6 Raji containing Luciferase) if performing in vivo CRS experiment. This should be completed 3 weeks prior to infusion of CAR-T into mice.

[0398] The following sERteps may be taken to provide CRS resistance. A selectable marker is required to enrich for this gene modification as cytokines are secreted proteins, thus. This example describes the making of a cell CAR19-GM-CSF PEBL, in which blockade of GM-CSF secretion mitigates risk of CRS. As those of skill in the art will recognize, certain of the steps may be conducted sequentially or out of the order listed below, though perhaps leading to different efficiency.

[0399] Step 1: T Cell Activation (Day 0)

[0400] Purify T cells from leukapheresis chamber using Miltenyi juman PanT isolation kit. Resuspend in media. Count cells. Determine number of human T cell activation CD3/CD28 beands required to obtain 3:1 bead:cell ratio. Wash beads 2.times. with T cell media. Dilute cells at 1.256 cells/mL in hXcyte media. Add human T cell activation CD3/CD28 beads. Aliquot 4 ml/well of 1.256 cells/mL solution into 6-well plate. Incubate at 37.degree. C.

[0401] Step 2: Transduction of T Cells with PEBL CAR (Day 1)

[0402] T cells are transduced with a CAR targeted to (i.e., that recognizes) one or more antigen or protein targets, for example with a Lentivirus containing a CAR construct targeting CD19, combined with the anti-GM-CSF PEBL. Expression from a polycistronic vector is preferable, allowing CD34 expression to mark both CAR and PEBL expression. However, expression can be achieved with the same viral vector expressing both the CAR and PEBL individually, or as independent transductions with separate vectors containing CAR and PEBL. Any other suitable method of transduction may be used, for example, AAV, retrovirus, etc, or through direct insertion of the CAR PEBL complex into a targeted location of the genome using homology directed repair and a donor vector containing the construct.

[0403] Step 3: Assessment of Td Efficiency (Day 10)

[0404] Take 5.times.10.sup.5 cells from each sample and analyze by flow cytometry. Wash samples with RB. Add 3 .mu.L of anti-CD34 PE antibody. Add 5.mu.L of CD3 APC and 2 .mu.L of anti-FAB BV421 (detects CAR transduction). Wash. Perform flow cytometry. Cells should be CD34-positive indicating expression of CAR and PEBL from a polycistronic vector. Harvest T cells (Day 11).

[0405] Purification of CAR-T cells. CAR+ (CD34+) and GC-CSF deficient (PEBL+) cells can be enriched using a CD34-positive selection on the Miltenyi Automacs. This enriches the GC-CSF suppressed cells and enriches CAR+ cells.

[0406] Step 4: Assessment of CAR-T Activity

[0407] Inject 3.times.10.sup.7 CAR-T cells per mouse I.P. Assess serum cytokine levels. (Day 12, Day 13, Day 14). Measure serum cytokine levels using Luminex multiplex profiling assay to check for elevations in CRS-related cytokines. Perform a 4-hour chromium release assay against target cells (Raji) to assess in vitro activity (Day 11).

[0408] PEBL constructs targeting GM-CSF are provided in FIG. 6 and Tables 17 and 18.

TABLE-US-00021 TABLE 17 Anti-GM-CSF PEBL Constructs (SEQ ID NOS 3071-3076, respectively) ER-Retention CD28 Leader V.sub.L Linker V.sub.H Domain 2a trCD34 MALPVTALLL DIELTQPPSVS GGGGS(n)n = QVQLVESGG EQKLISEEDL PLALLLHAAR VAPGQTARIS 1, 2, 3, 4 GLVQPGGSLR KDEL (SEQ ID P (SEQ ID CSGDNLPGKY (SEQ LSCAASGFTF NO: 3028) NO: 1) VHWYQQKPG ID NO: 3069) SSHWMSWVR QAPVLVIYYD QAPGKGLEW SNRPSGIPERF VSNIWRGPYI SGSNSGNTAT YYADSVKGR LTISGTQAED FTISRDNSKNT EADYYCQSRT LYLQMNSLR QTTIVFGGGT AEDTAVYYC KLTVLGQ ARFQGYGGG (SEQ ID FDYWGQGTL NO: 3026) VTVSS (SEQ ID NO: 3027) MALPVTALLL DIELTQPPSVS GGGGS(n)n = QVQLVESGG (GGGGS).sub.4AEK PLALLLHAAR VAPGQTARIS 1, 2, 3, 4 GLVQPGGSLR DEL (SEQ ID P (SEQ ID CSGDNLPGKY (SEQ LSCAASGFTF NO: 3029) NO: 1) VHWYQQKPG ID NO: 3069) SSHWMSWVR QAPVLVIYYD QAPGKGLEW SNRPSGIPERF VSNIWRGPYI SGSNSGNTAT YYADSVKGR LTISGTQAED FTISRDNSKNT EADYYCQSRT LYLQMNSLR QTTIVFGGGT AEDTAVYYC KLTVLGQ ARFQGYGGG (SEQ ID NO: FDYWGQGTL 3026) VTVSS (SEQ ID NO: 3027) MALPVTALLL DIELTQPPSVS GGGGS(n)n = QVQLVESGG TTTPAPRPPTP PLALLLHAAR VAPGQTARIS 1, 2, 3, 4 GLVQPGGSLR APTIASQPLSL P (SEQ ID CSGDNLPGKY (SEQ LSCAASGFTF RPEACRPAAG NO: 1) VHWYQQKPG ID NO: 3069) SSHWMSWVR GAVHTRGLDF QAPVLVIYYD QAPGKGLEW ACDIYIWAPL SNRPSGIPERF VSNIWRGPYI AGTCGVLLLS SGSNSGNTAT YYADSVKGR LVITLYCNHR LTISGTQAED FTISRDNSKNT NLYKYKSRRS EADYYCQSRT LYLQMNSLR FEDEKKMP QTTIVFGGGT AEDTAVYYC (SEQ ID KLTVLGQ ARFQGYGGG NO: 3030) (SEQ ID NO: FDYWGQGTL 3026) VTVSS (SEQ ID NO: 3027) MALPVTALLL DIELTQPPSVS GGGGS(n)n = QVQLVESGG EQKLISEEDL GSGATNFSLL MPRGWTALC PLALLLHAAR VAPGQTARIS 1, 2, 3, 4 GLVQPGGSLR KDEL (SEQ ID KQAGDVEEN LLSLLPSGFM P (SEQ ID CSGDNLPGKY (SEQ LSCAASGFTF NO: 3028) PGP (SEQ ID SLDNNGTATP NO: 1) VHWYQQKPG ID NO: 3069) SSHWMSWVR NO: 3031) ELPTQGTFSN QAPVLVIYYD QAPGKGLEW VSTNVSYQET SNRPSGIPERF VSNIWRGPYI TTPSTLGSTSL SGSNSGNTAT YYADSVKGR HPVSQHGNEA LTISGTQAED FTISRDNSKNT TTNITETTVKF EADYYCQSRT LYLQMNSLR TSTSVITSVYG QTTIVFGGGT AEDTAVYYC NTNSSVQSQT KLTVLGQ ARFQGYGGG SVISTVFTTPA (SEQ ID NO: FDYWGQGTL NVSTPETTLK 3026) VTVSS (SEQ PSLSPGNVSD ID NO: 3027) LSTTSTSLATS PTKPYTSSSPI LSDIKAEEKCS GIREVKLTQGI CLEQNKTSSC AEFKKDRGEG LARVLCGEEQ ADADAGAQV CSLLLAQSEV RPQCLLLVLA NRTEISSKLQL MKKHQSDLK KLGILDFTEQ DVASHQSYSQ KTLIALVTSG ALLAVLGITG YFLMNRRSW SPI (SEQ ID NO: 3032) MALPVTALLL D1ELTQPPSVS GGGGS(n)n = QVQLVESGG (GGGGS)4AEK GSGATNFSLL MPRGWTALC PLALLLHAAR VAPGQTARIS 1, 2, 3, 4 GLVQPGGSLR DEL (SEQ ED KQAGDVEEN LLSLLPSGFM P (SEQ ID CSGDNLPGKY (SEQ LSCAASGFTF NO: 3029) PGP (SEQ ID SLDNNGTATP NO: 1) VHWYQQKPG ID NO: 3069) SSHWMSWVR NO: 3031) ELPTQGTFSN QAPVLVIYYD QAPGKGLEW VSTNVSYQET SNRPSGIPERF VSNIWRGPYI TTPSTLGSTSL SGSNSGNTAT YYADSVKGR HPVSQHGNEA LTISGTQAED FTISRDNSKNT TTNITETTVKF EADYYCQSRT LYLQMNSLR TSTSVITSVYG QTTIVFGGGT AEDTAVYYC NTNSSVQSQT KLTVLGQ ARFQGYGGG SVISTVFTTPA (SEQ ID NO: FDYWGQGTL NVSTPETTLK 3026) VTVSS (SEQ PSLSPGNVSD ID NO: 3027) LSTTSTSLATS PTKPYTSSSPI LSDIKAEEKCS GIREVKLTQGI CLEQNKTSSC AEFKKDRGEG LARVLCGEEQ ADADAGAQV CSLLLAQSEV RPQCLLLVLA NRTEISSKLQL MKKHQSDLK KLGILDFTEQ DVASHQSYSQ KTLIALVTSG ALLAVLGITG YFLMNRRSW SPI (SEQ ID NO: 3032) MALPVTALLL D1ELTQPPSVS GGGGS(n)n = QVQLVESGG TTTPAPRPPTP GSGATNFSLL MPRGWTALC PLALLLHAAR VAPGQTARIS 1, 2, 3, 4 GLVQPGGSLR APTIASQPLSL KQAGDVEEN LLSLLPSGFM P (SEQ ID CSGDNLPGKY (SEQ LSCAASGFTF RPEACRPAAG PGP (SEQ ID SLDNNGTATP NO: 1) VHWYQQKPG ID NO: 3069) SSHWMSWVR GAVHTRGLDF NO: 3031) ELPTQGTFSN QAPVLVIYYD QAPGKGLEW ACDIYIWAPL VSTNVSYQET SNRPSGIPERF VSNIWRGPYI AGTCGVLLLS TTPSTLGSTSL SGSNSGNTAT YYADSVKGR LVITLYCNHR HPVSQHGNEA LTISGTQAED FTISRDNSKNT NLYKYKSRRS TTNITETTVKF EADYYCQSRT LYLQMNSLR FEDEKKMP TSTSVITSVYG QTTIVFGGGT AEDTAVYYC (SEQ ID NO: NTNSSVQSQT KLTVLGQ ARFQGYGGG 3030) SVISTVFTTPA (SEQ ID NO: FDYWGQGTL NVSTPETTLK 3026) VTVSS (SEQ PSLSPGNVSD ID NO: 3027) LSTTSTSLATS PTKPYTSSSPI LSDIKAEEKCS GIREVKLTQGI CLEQNKTSSC AEFKKDRGEG LARVLCGEEQ ADADAGAQV CSLLLAQSEV RPQCLLLVLA NRTEISSKLQL MKKHQSDLK KLGILDFTEQ DVASHQSYSQ KTLIALVTSG ALLAVLGITG YFLMNRRSW SPI (SEQ ID NO: 3032)

TABLE-US-00022 TABLE 18 CD19 CAR with GM-CSF PEBL Constructs (SEQ ID NOS 3077-3082, respectively) ER- CD28 Retention CD8a CD19 CD19 CD8a CD28 Co- CD8a Domain Leader V.sub.H Linker V.sub.L Hinge tm stim CD3z 2a Leader V.sub.L Linker V.sub.H and Tag 2a Tag MAL DIQ GGG EVK TTT FWV RSK RVK GSG MAL DIE GGG QVQ EQK PVT MTQ GS.sub.4 LQE PAP LVV RSR FSR ATN PVT LTQ GS(n)n LVE LISE ALL TTS (SEQ SGP RPP VGG LLH SAD FSL ALL PPS = SGG EDL LPL SLS ID GLV TPA VLA SDY APA LKQ LPL VSV 1, 2, GLV KDE ALL ASL NO: APS PTIA CYS MN YKQ AGD ALL APG 3, 4 QPG L LHA GDR 9) QSL SQP LLV MTP GQN VEE LHA QTA (SEQ GSL (SEQ ARP VTIS SVT LSL TVA RRP QLY NPG ARP RISC ID RLS ID (SEQ CRA CTV RPE FIIF GPT NEL P (SEQ SGD NO: CAA NO: ID SQD SGV ACR WV RKH NLG (SEQ ID NLP 3069) SGF 3028) NO: 1) ISK SLP PAA (SEQ YQP RRE ID NO: 1) GKY TFS YLN DYG GGA ID YAP EYD NO: VH SHW WY VSW VHT NO: PRD VLD 3031) WY MS QQK IRQ RGL 3036) FAA KRR QQK WV PDG PPR DFA YRS GRD PGQ RQA TVK KGL CD (SEQ PEM APV PGK LLI EWL (SEQ ID GGK LVI GLE YHT GVI ID NO: PRR YYD WVS SRL WGS NO: 3037) KNP SNR NIW HSG ETT 3035) QEG PSGI RGP VPS YYN LYN PER YIY RFS SAL ELQ FSG YAD GSG KSR KDK SNS SVK SGT LTII MAE GNT GRF DYS KDN AYS ATL TISR LTIS SKS EIG TISG DNS NLE QVF MK TQA KNT QED LKM GER EDE LYL IAT NSL RRG ADY QM YFC QTD KGH YCQ NSL QQG DTA DGL SRT RAE NTL IYY YQG QTT DTA PYT CAK LST IVF VYY FGG HYY ATK GGG CAR GTK YGG DTY TKL FQG LEIT SYA DAL TVL YGG RAD MD HM GQ GFD AAP YW QAL (SEQ YW TVSI GQG PPR ID GQG FPPS TSV (SEQ NO: TLV SN TVS ID 3026) TVS (SEQ S NO: S ID (SEQ 3038) (SEQ NO: ID ID 3033) NO: NO: 3034) 3027) MAL DIQ GGG EVK TIT FWV RSK RVK GSG MAL DIE GGG QVQ (GG PVT MTQ GS.sub.4 LQE PAP LVV RSR FSR ATN PVT LTQ GS(n)n LVE GGS).sub.4 ALL rrs (SEQ SGP RPP VGG LLH SAD FSL ALL PPS = SGG AE LPL SLS ID GLV TPA VLA SDY APA LKQ LPL VSV 1, 2, GLV KDE ALL ASL NO: APS PTIA CYS MN YKQ AGD ALL APG 3, 4 QPG L LHA GDR 9) QSL SQP LLV MTP GQN VEE LHA QTA (SEQ GSL (SEQ ARP VTIS SVT LSL TVA RRP QLY NPG ARP RISC ID RLS ID (SEQ CRA CTV RPE FIIF GPT NEL P (SEQ SGD NO: CAA NO: ID SQD SGV ACR WV RKH NLG (SEQ ID NLP 3069) SGF 3029) NO: 1) ISK SLP PAA (SEQ YQP RRE ID NO: 1) GKY TFS YLN DYG GGA ID YAP EYD NO: VH SHW WY VSW VHT NO: PRD VLD 3031) WY MS QQK IRQ RGL 3036) FAA KRR QQK WV PDG PPR DFA YRS GRD PGQ RQA TVK KGL CD (SEQ PEM APV PGK LLI EWL (SEQ ID GGK LVI GLE YHT GVI ID NO: PRR YYD WVS SRL WGS NO: 3037) KNP SNR NIW HSG ETT 3035) QEG PSGI RGP VPS YYN LYN PER YIY RFS SAL ELQ FSG YAD GSG KSR KDK SNS SVK SGT LTII MAE GNT GRF DYS KDN AYS ATL TISR LTIS SKS EIG TISG DNS NLE QVF MK TQA KNT QED LKM GER EDE LYL IAT NSL RRG ADY QM YFC QTD KGH YCQ NSL QQG DTA DGL SRT RAE NTL IYY YQG QTT DTA PYT CAK LST IVF VYY FGG HYY ATK GGG CAR GTK YGG DTY TKL FQG LEIT SYA DAL TVL YGG RAD MD HM GQ GFD AAP YW QAL (SEQ YW TVSI GQG PPR ID GQG FPPS TSV (SEQ NO: TLV SN TVS ID 3026) TVS (SEQ S NO: S ID (SEQ 3038) (SEQ NO: ID ID 3033) NO: NO: 3034) 3027) MAL DIQ GGG EVK TIT FWV RSK RVK GSG MAL DIE GGG QVQ TTT PVT MTQ GS.sub.4 LQE PAP LVV RSR FSR ATN PVT LTQ GS(n)n LVE PAP ALL rrs (SEQ SGP RPP VGG LLH SAD FSL ALL PPS = SGG RPP LPL SLS ID GLV TPA VLA SDY APA LKQ LPL VSV 1, 2, GLV TPA ALL ASL NO: APS PTIA CYS MN YKQ AGD ALL APG 3, 4 QPG PTIA LHA GDR 9) QSL SQP LLV MTP GQN VEE LHA QTA (SEQ GSL SQP ARP VTIS SVT LSL TVA RRP QLY NPG ARP RISC ID RLS LSL (SEQ CRA CTV RPE FIIF GPT NEL P (SEQ SGD NO: CAA RPE ID SQD SGV ACR WV RKH NLG (SEQ ID NLP 3069) SGF ACR NO: 1) ISK SLP PAA (SEQ YQP RRE ID NO: 1) GKY TFS PAA YLN DYG GGA ID YAP EYD NO: VH SHW GGA WY VSW VHT NO: PRD VLD 3031) WY MS VHT QQK IRQ RGL 3036) FAA KRR QQK WV RGL PDG PPR DFA YRS GRD PGQ RQA DFA TVK KGL CD (SEQ PEM APV PGK CDI LLI EWL (SEQ ID GGK LVI GLE YIW YHT GVI ID NO: PRR YYD WVS APL SRL WGS NO: 3037) KNP SNR NIW AGT HSG ETT 3035) QEG PSGI RGP CGV VPS YYN LYN PER YIY LLL RFS SAL ELQ FSG YAD SLVI GSG KSR KDK SNS SVK TLY SGT LTII MAE GNT GRF CNH DYS KDN AYS ATL TISR RNL LTIS SKS EIG TISG DNS YKY NLE QVF MK TQA KNT KSR QED LKM GER EDE LYL RSFI IAT NSL RRG ADY QM DEK YFC QTD KGH YCQ NSL KMP QQG DTA DGL SRT RAE (SEQ NTL IYY YQG QTT DTA D PYT CAK LST IVF VYY NO: FGG HYY ATK GGG CAR 3030) GTK YGG DTY TKL FQG LEIT SYA DAL TVL YGG RAD MD HM GQ GFD AAP YW QAL (SEQ YW TVSI GQG PPR ID GQG FPPS TSV (SEQ NO: TLV SN TVS ID 3026) TVS (SEQ S NO: S ID (SEQ 3038) (SEQ NO: ID ID 3033) NO: NO: 3034) 3027) MAL DIQ GGG EVK TIT FWV RSK RVK GSG MAL DIE GGG QVQ EDL FSL TAL PVT MTQ GS.sub.4 LQE PAP LVV RSR FSR ATN PVT LTQ GS(n)n LVE KDE LKQ CLL ALL rrs (SEQ SGP RPP VGG LLH SAD FSL ALL PPS = SGG L AGD SLL LPL SLS ID GLV TPA VLA SDY APA LKQ LPL VSV 1, 2, GLV (SEQ VEE PSG ALL ASL NO: APS PTIA CYS MN YKQ AGD ALL APG 3, 4 QPG ID NPG FMS LHA GDR 9) QSL SQP LLV MTP GQN VEE LHA QTA (SEQ GSL NO: P LDN ARP VTIS SVT LSL TVA RRP QLY NPG ARP RISC ID RLS 3028) (SEQ NGT (SEQ CRA CTV RPE FIIF GPT NEL P (SEQ SGD NO: CAA ID ATP ID SQD SGV ACR WV RKH NLG (SEQ ID NLP 3069) SGF NO: ELP NO: 1) ISK SLP PAA (SEQ YQP RRE ID NO: 1) GKY TFS 3031) TQG YLN DYG GGA ID YAP EYD NO: VH SHW TFS WY VSW VHT NO: PRD VLD 3031) WY MS NVS QQK IRQ RGL 3036) FAA KRR QQK WV TNV PDG PPR DFA YRS GRD PGQ RQA SYQ TVK KGL CD (SEQ PEM APV PGK ETT LLI EWL (SEQ ID GGK LVI GLE TPS YHT GVI ID NO: PRR YYD WVS TLG SRL WGS NO: 3037) KNP SNR NIW STS HSG ETT 3035) QEG PSGI RGP LHP VPS YYN LYN PER YIY VSQ RFS SAL ELQ FSG YAD HGN GSG KSR KDK SNS SVK EAT SGT LTII MAE GNT GRF TNI DYS KDN AYS ATL TISR TET LTIS SKS EIG TISG DNS TVK NLE QVF MK TQA KNT FTS QED LKM GER EDE LYL TSVI IAT NSL RRG ADY QM TSV YFC QTD KGH YCQ NSL YGN QQG DTA DGL SRT RAE TNS NTL IYY YQG QTT DTA SVQ PYT CAK LST IVF VYY SQT FGG HYY ATK GGG CAR SVIS GTK YGG DTY TKL FQG TVF LEIT SYA DAL TVL YGG TIP RAD MD HM GQ GFD ANV AAP YW QAL (SEQ YW STP TVSI GQG PPR ID GQG ETT FPPS TSV (SEQ NO: TLV LKP SN TVS ID 3026) TVS SLS (SEQ S NO: S PGN ID (SEQ 3038) (SEQ VSD NO: ID ID LST 3033) NO: NO: TST 3034) 3027) SLA TSP TKP YTS SSPI LSDI KAE IKC SGI REV KLT QGI CLE QNK TSS CAE FKK DRG EGL ARV LCG EEQ ADA DAD AQV CSL LLA QSE VRP QCL LLV LAN RTEI SSK LQL MK KHQ SDL KKL GIL DFT EQD VAS HQS YSQ KTL IAL VTS GAL LAV LGI TGY FLM NRR SWS PI (SEQ ID NO:

10) MAL DIQ GGG EVK TIT FWV RSK RVK GSG MAL DIE GGG QVQ (GG FSL TAL PVT MTQ GS.sub.4 LQE PAP LVV RSR FSR ATN PVT LTQ GS(n)n LVE GGS).sub.4 LKQ CLL ALL rrs (SEQ SGP RPP VGG LLH SAD FSL ALL PPS = SGG AE AGD SLL LPL SLS ID GLV TPA VLA SDY APA LKQ LPL VSV 1, 2, GLV KDE VEE PSG ALL ASL NO: APS PTIA CYS MN YKQ AGD ALL APG 3, 4 QPG L NPG FMS LHA GDR 9) QSL SQP LLV MTP GQN VEE LHA QTA (SEQ GSL (SEQ P LDN ARP VTIS SVT LSL TVA RRP QLY NPG ARP RISC ID RLS ID (SEQ NGT (SEQ CRA CTV RPE FIIF GPT NEL P (SEQ SGD NO: CAA NO: ID ATP ID SQD SGV ACR WV RKH NLG (SEQ ID NLP 3069) SGF 3029) NO: ELP NO: 1) ISK SLP PAA (SEQ YQP RRE ID NO: 1) GKY TFS 3031) TQG YLN DYG GGA ID YAP EYD NO: VH SHW TFS WY VSW VHT NO: PRD VLD 3031) WY MS NVS QQK IRQ RGL 3036) FAA KRR QQK WV TNV PDG PPR DFA YRS GRD PGQ RQA SYQ TVK KGL CD (SEQ PEM APV PGK ETT LLI EWL (SEQ ID GGK LVI GLE TPS YHT GVI ID NO: PRR YYD WVS TLG SRL WGS NO: 3037) KNP SNR NIW STS HSG ETT 3035) QEG PSGI RGP LHP VPS YYN LYN PER YIY VSQ RFS SAL ELQ FSG YAD HGN GSG KSR KDK SNS SVK EAT SGT LTII MAE GNT GRF TNI DYS KDN AYS ATL TISR TET LTIS SKS EIG TISG DNS TVK NLE QVF MK TQA KNT FTS QED LKM GER EDE LYL TSVI IAT NSL RRG ADY QM TSV YFC QTD KGH YCQ NSL YGN QQG DTA DGL SRT RAE TNS NTL IYY YQG QTT DTA SVQ PYT CAK LST IVF VYY SQT FGG HYY ATK GGG CAR SVIS GTK YGG DTY TKL FQG TVF LEIT SYA DAL TVL YGG TIP RAD MD HM GQ GFD ANV AAP YW QAL (SEQ YW STP TVSI GQG PPR ID GQG ETT FPPS TSV (SEQ NO: TLV LKP SN TVS ID 3026) TVS SLS (SEQ S NO: S PGN ID (SEQ 3038) (SEQ VSD NO: ID ID LST 3033) NO: NO: TST 3034) 3027) SLA TSP TKP YTS SSPI LSDI KAE IKC SGI REV KLT QGI CLE QNK TSS CAE FKK DRG EGL ARV LCG EEQ ADA DAD AQV CSL LLA QSE VRP QCL LLV LAN RTEI SSK LQL MK KHQ SDL KKL GIL DFT EQD VAS HQS YSQ KTL IAL VTS GAL LAV LGI TGY FLM NRR SWS PI (SEQ ID NO: 10) MAL DIQ GGG EVK TIT FWV RSK RVK GSG MAL DIE GGG QVQ TTT FSL TAL PVT MTQ GS.sub.4 LQE PAP LVV RSR FSR ATN PVT LTQ GS(n)n LVE PAP LKQ CLL ALL rrs (SEQ SGP RPP VGG LLH SAD FSL ALL PPS = SGG RPP AGD SLL LPL SLS ID GLV TPA VLA SDY APA LKQ LPL VSV 1, 2, GLV TPA VEE PSG ALL ASL NO: APS PTIA CYS MN YKQ AGD ALL APG 3, 4 QPG PTIA NPG FMS LHA GDR 9) QSL SQP LLV MTP GQN VEE LHA QTA (SEQ GSL SQP P LDN ARP VTIS SVT LSL TVA RRP QLY NPG ARP RISC ID RLS LSL (SEQ NGT (SEQ CRA CTV RPE FIIF GPT NEL P (SEQ SGD NO: CAA RPE ID ATP ID SQD SGV ACR WV RKH NLG (SEQ ID NLP 3069) SGF ACR NO: ELP NO: 1) ISK SLP PAA (SEQ YQP RRE ID NO: 1) GKY TFS PAA 3031) TQG YLN DYG GGA ID YAP EYD NO: VH SHW GGA TFS WY VSW VHT NO: PRD VLD 3031) WY MS VHT NVS QQK IRQ RGL 3036) FAA KRR QQK WV RGL TNV PDG PPR DFA YRS GRD PGQ RQA DFA SYQ TVK KGL CD (SEQ PEM APV PGK CDI ETT LLI EWL (SEQ ID GGK LVI GLE YIW TPS YHT GVI ID NO: PRR YYD WVS APL TLG SRL WGS NO: 3037) KNP SNR NIW AGT STS HSG ETT 3035) QEG PSGI RGP CGV LHP VPS YYN LYN PER YIY LLL VSQ RFS SAL ELQ FSG YAD SLVI HGN GSG KSR KDK SNS SVK TLY EAT SGT LTII MAE GNT GRF CNH TNI DYS KDN AYS ATL TISR RNL TET LTIS SKS EIG TISG DNS YKY TVK NLE QVF MK TQA KNT KSR FTS QED LKM GER EDE LYL RSFI TSVI IAT NSL RRG ADY QM DEK TSV YFC QTD KGH YCQ NSL KMP YGN QQG DTA DGL SRT RAE (SEQ TNS NTL IYY YQG QTT DTA D SVQ PYT CAK LST IVF VYY NO: SQT FGG HYY ATK GGG CAR 3030) SVIS GTK YGG DTY TKL FQG TVF LEIT SYA DAL TVL YGG TIP RAD MD HM GQ GFD ANV AAP YW QAL (SEQ YW STP TVSI GQG PPR ID GQG ETT FPPS TSV (SEQ NO: TLV LKP SN TVS ID 3026) TVS SLS (SEQ S NO: S PGN ID (SEQ 3038) (SEQ VSD NO: ID ID LST 3033) NO: NO: TST 3034) 3027) SLA TSP TKP YTS SSPI LSDI KAE IKC SGI REV KLT QGI CLE QNK TSS CAE FKK DRG EGL ARV LCG EEQ ADA DAD AQV CSL LLA QSE VRP QCL LLV LAN RTEI SSK LQL MK KHQ SDL KKL GIL DFT EQD VAS HQS YSQ KTL IAL VTS GAL LAV LGI TGY FLM NRR SWS PI (SEQ ID NO: 10)

Example 17

In Vitro CRS Assay for Testing Efficacy of Inducing CRS After Deletion of GM-CSF in CART19

[0409] Cell lines: CD19 positive B-ALL cell line RAMOS was used to evaluate CRS in an in vitro assay. Prior to assay, RAMOS cells were stably transfected with GFP using lentiviral transduction and cultured in RPMI +10% FBS+Pen/Strep.

[0410] Isolation of normal donor monocytes and T cells: Primary human T cells and monocytes were isolated from normal healthy human donors. T cell cells were isolated from PBMC using CD4+CD8+ selection (Miltenyi Biotec) and monocytes were separated using Miltenyi biotec classical Monocyte Isolation beads according to the manufactures protocol.

[0411] T cell culture and CAR-T gene editing: T cells were subsequently resuspended at a concentration of 1.times.10.sup.6 cells/mL in Xcyte media supplemented with 50 U/mL IL-2 and 10 ng/ml IL-15 in the presence of anti-CD3/CD28 beads (Bead to cell ratio 3:1). Twenty-four hours after initial stimulation, T cells were transfected with lentiviral vector encoding the CD19 CAR construct in the presence of polybrene (final conc. 6 .mu.g/ml). Stimulatory beads were removed on day 2. CART19 cells were suspended at 4.times.10.sup.6 T cells were electroporated in 100 .mu.l buffer P3 with 15 .mu.g spCas9 mRNA (Trilink CA.) and 20 .mu.g of GM-CSF gRNA (Trilink) using a nucleofector 4D, program EO-115. Control CAR19 T cells were electroporated without GM-CSF gRNA. T-cells were subsequently evaluated at day 6 for CD34 (bicistronic marker of CAR-T) and intracellular GM-CSF expression using flowcytometry prior to co-culture assay.

[0412] Production of monocyte lineage cells: For iDC generation, monocytes (1.times.10.sup.6) were plated in 6 mLs of RPMI 1640 supplemented with supplemented with 0.1 mmol/L MEM Non-Essential Amino Acids, 2 mmol/L L-glutamine, 100 units/mL penicillin, 100 .mu.g/mL streptomycin (Life Technologies) and 10% fetal calf serum (cR10). cR10 was subsequently supplemented with 0.2 .mu.g/mL human IL-4 (Peptotec) and 0.2 .mu.g/mL GM-CSF (Peptotec).

[0413] For macrophage and activated macrophage generation cR10 was supplemented with 10% human AB serum instead of fetal calf serum (hR10). For activated macrophages hR10 medium was supplemented with 30 ng/ml of LPS. On day 4 cytokines and LPS were replenished. Macrophages, activated macrophages and iDC were harvested using 2 mmol/L EDTA (immature dendritic cells) on day 6 post-isolation. Twenty-four hours later, cells were harvested with 2 mmol/L EDTA and stained with CD45, CD80 and CD86 to confirm immature DC and mature DC differentiation.

[0414] Co-culture assay: CAR-T cells were combined at the following ratios in 200 ul per 96 well: 12.5K UCART-19 (with or with-out GM-CSF KO), Target, 50K Ramos cells (CD19+) and monocyte derived cells, 1K iDC or 5K macrophages or 5K activated macrophages.

[0415] Co-cultures were subsequently incubated for at 37.degree. C. and 100 ul of assay supernatant was collected at 24 hr and 48 hr for cytokine analysis.

[0416] Measurement of Cytokine Levels

[0417] Cytokine concentration determination from culture supernatants was performed using IL-6 ELISA plate (R&D systems). Prior to analysis supernatant's were centrifuged at 300 g for 10 mins at 4.degree. C. and subsequently diluted 1:10 in assay calibrator diluent. Measurements were performed using standard product protocols.

[0418] GM-CSF deficient CART19 induced significantly lower it-6 expression across the different monocyte lineages. FIGS. 8 and 10

Example 18

In Vitro CRS Assay for Testing Efficacy of Inducing CRS after Deletion of GM-CSF in T Cells

[0419] Isolation of normal donor monocytes and T cells: Primary human T cells and monocytes were isolated from normal healthy human donors. T cell cells were isolated from PBMC using CD4+CD8+ selection (Miltenyi Biotec) and monocytes were separated using Miltenyi Biotec classical Monocyte Isolation beads according to the manufactures protocol.

[0420] T cell culture and gene editing: T cells were subsequently resuspended at a concentration of 106 cells/mL in Xcyte media supplemented with 50 U/mL IL-2 and 10 ng/ml IL-15 in the presence of anti-CD3/CD28 beads (Bead to cell ratio 3:1) (Life Technologies, catalog #111.32D). Twenty-four hours after initial stimulation. Stimulatory beads were removed on day 2. 4.times.10.sup.6 T cells were electroporated in 100 .mu.l buffer P3 with 15 .mu.g spCas9 mRNA (Trilink CA.) and 20 .mu.g of TRAC gRNA (Trilink) using a nucleofector 4D, program EO-115. Control CAR19 T cells were electroporated without GM-CSF gRNA. T-cells were subsequently evaluated at day 6 for GM-CSF expression prior to co-culture assay using flowcytometry.

[0421] Production of monocyte lineage cells: For iDC generation, monocytes (1.times.10.sup.6) were plated in 6 mLs of RPMI 1640 supplemented with supplemented with 0.1 mmol/L MEM Non-Essential Amino Acids, 2 mmol/L L-glutamine, 100 units/mL penicillin, 100 .mu.g/mL streptomycin (Life Technologies) and 10% fetal calf serum (cR10). cR10 was subsequently supplemented with 0.2 .mu.g/mL human IL-4 (Peptotec) and 0.2 .mu.g/mL GM-CSF (Peptotec). On day 4 cytokines and LPS were replenished. iDC were harvested using 2 mmol/L EDTA (immature dendritic cells) on day 6 post-isolation.

[0422] Co-culture assay: T cells were combined at the following ratios in 200 ul per 96 well: 12.5K T cells (with or with-out GM-CSF KO), 50K anti-CD3/CD28 beads and 1K iDC Co-cultures were subsequently incubated for at 37.degree. C. and 100 ul of assay supernatant was collected at 24 hr and 48 hr for cytokine analysis.

[0423] Measurement of cytokine levels: Cytokine concentration determination from culture supernatants was performed using IL-6 ELISA plate (R&D systems). Prior to analysis supernatants were centrifuged at 300.times.g for 10 mins at 4.degree. C. and subsequently diluted 1:10 in assay calibrator diluent. Measurements were performed using standard product protocols.

[0424] Deletion of GM-CSF reduced IL-6 production >3-fold at 24 hrs (FIGS. 7 and 8) and >4-fold at 48 hrs (FIGS. 9 and 10) relative to non-edited T cells.

[0425] GM-CSF deficient T cells induced significantly lower IL-6 expression across the different monocyte lineages.

Example 19

Method for Making and Testing a Genome-Edited CAR-T Cell Deficient at Inducing CRS by Insertion of Selectable Marker into Gene Edited Locus

[0426] Inject primary B-ALL (2.times.10.sup.6) in NSG mice if performing an in vivo CRS experiment. This should be completed 3 weeks prior to infusion of CAR-T into mice.

[0427] The following steps may be taken to provide a genome-edited, CRS-resistant, CAR-T cells. This example describes the making of a CD19CART.DELTA.GMCSF.DELTA.CD3.epsilon. mutant IL-7R T cell, in which the deletion of GM-CSF mitigates risk of CRS, deletion of CD3e prevent TCR signaling and GvHD and the mutant IL-7R enhances proliferation of the CAR-T sufficiently to induce CRS in this model. Sequences encoding a mutant, constitutively active IL-7R sequence can be found in Table 19, or found in the art. As those of skill in the art will recognize, certain of the steps may be conducted sequentially or out of the order listed below, though perhaps leading to different efficiency.

[0428] Step 1: T Cell Activation (Day 0)

[0429] Purify T cells from a leukapheresis chamber using a Miltenyi human PanT isolation kit. Resuspend in media. Count cells. Determine the number of human T cell activation CD3/CD28 beads required to obtain a 3:1 bead:cell ratio. Wash beads 2.times. with T cell media. Dilute cells at 1.256 cells/mL in hXcyte media. Add human T cell activation CD3/CD28 beads. Aliquot 4 mL/well of 1.256 cell/mL solution into a 6 well plate. Incubate cells at 37.degree. C.

[0430] Step 2: T Cell Transduction (Day 1)

[0431] CAR-T cells may then be transduced with one or more CARs targeted to (i.e., that recognizes) one or more targets, for example with a lentivirus containing a CAR construct. Any other suitable method of transduction may be used.

[0432] Step 3: CRISPR (Day 2)

[0433] In a CRS-resistant CAR-T cell, cytokine/chemokine/transcription factor genes or transcription factors may be deleted to prevent secretion of factors that induce secretion of cytokines from myeloid cells. Deletion may be accomplished by electroporating with Cas9 mRNA and gRNA against the target(s). Other techniques, however, could be used to suppress expression of the target. These include other genome editing techniques such as TALENs, RNA interference, and eliciting of internal binding of the antigen to prevent cell surface expression. Examples of gRNAs that may be used include those shown in Tables 8-10, and others known in the art.

TABLE-US-00023 Nuecleofection Sample ID gRNA#1 gRNA#2 Cas9 Buffer P3 UCART19 20 .mu.g 20 .mu.g 15 .mu.g Cas9 100 .mu.l gGM-CSF gCD3.epsilon. mRNA

[0434] Cells are harvested, isolated, and purified, for example using magnetic selection with a labelled antibody-coated magnetic beads that bind to a cell-specific protein (available from, e.g., Miltenyi Biotec). For T cells, anti-CD3/CD28 beads could be used. Other purification techniques are known in the art and could be used.

TABLE-US-00024 TABLE 19 Sequences for Constitutively Expressing IL-7R Truc- Truc- CD28 Trunc- ated ated CD8a CD19 CD19 CD8a CD28 Co- ated IL-7R IL-7 IL-7R Leader V.sub.L Linker V.sub.H Hinge tm stim CD3z 2a CD34 ECD TMD ICD Description MALP DIQM GGGG EVKL TTTPA FWVL RSKR RVKF GSGA MPRG YREG LLTCP KKRI IL7R VTAL TQTTS S.sub.4 QESG PRPPT VVVG SRLL SRSA TNFSL WTAL ANDF TISILS KPIV with L5 LLPLA SLSAS (SEQ PGLV PAPTI GVLA HSDY DAPA LKQA CLLSL VVTF FFSVA WPSL and L6 LLLH LGDR ID NO: APSQS ASQP CYSL MNMT YKQG GDVE LPSGF NTSH LLVIL PDHK elbows AARP VTISC 9) LSVT LSLRP LVTV PRRP QNQL ENPG MSLD LQKK ACVL KTLE with (SEQ RASQ CTVS EACR AFIIF GPTR YNEL P (SEQ NNGT YVKV W HLCK CPT ID DISKY GVSL PAAG WV KHYQ NLGR ID NO: ATPEL LMHD (SEQ KPRK trans- NO: 1) LNWY PDYG GAVH (SEQ PYAPP REEY 3031) PTQG VAYR ID NLNV membrane QQKP VSWI TRGL ID NO: RDFA DVLD TFSN QEKD NO: SFNPE T- DGTV RQPP DFAC 3036) AYRS KRRG VSTN ENKW 3045) SFLDC ALL KLLIY RKGL D (SEQ RDPE VSYQ THVN QIHR mutation HTSR EWLG (SEQ ID NO: MGGK ETTTP LSSTK VDDI insertion LHSG VIWG ID NO: 3037) PRRK STLGS LTLL QARD only VPSRF SETTY 3035) NPQE TSLHP QRKL EVEG SGSGS YNSA GLYN VSQH QPAA FLQD GTDY LKSR ELQK GNEA MYEI TFPQ SLTIS LTIIK DKMA TTNIT KVRSI QLEES NLEQ DNSK EAYS ETTV PDHY EKQR EDIAT SQVF EIGM KFTST FKGF LGGD YFCQ LKMN KGER SVITS WSEW VQSP QGNT SLQT RRGK VYGN SPSYY NCPSE LPYTF DDTAI GHDG TNSS FRTPE DVVIT GGGT YYCA LYQG VQSQ INNSS PESFG KLEIT KHYY LSTAT TSVIS GEMD RDSSL RADA YGGS KDTY TVFTT PI TCLA APTV YAMD DALH PANV (SEQ GNVS SIFPPS YWGQ MQAL STPET ID ACDA SN GTSV PPR TLKPS NO: PILSS (SEQ TVSS (SEQ LSPG 3040) SRSLD ID (SEQ ID NO: NVSD CRES NO: ID 3038) LSTTS GKNG 3033) NO: TSLAT PHVY 3034) SPTKP QDLL YTSSS LSLGT PILSDI TNSTL KAEIK PPPFS CSGIR LQSGI EVKL LTLNP TQGIC VAQG LEQN QPILT KTSSC SLGS AEFK NQEE KDRG AYVT EGLA MSSF RVLC YQNQ GEEQ (SEQ ADAD ID AGAQ NO: VCSL 3047) LLAQ SEVRP QCLL LVLA NRTEI SSKL QLMK KHQS DLKK LG (SEQ ID NO: 3039) MALP DIQM GGGG EVKL TTTPA FWVL RSKR RVKF GSGA MPRG YREG LLTCP KKRI IL7R VTAL TQTTS S.sub.4 QESG PRPPT VVVG SRLL SRSA TNFSL WTAL ANDF TISILS KPIV with L5 LLPLA SLSAS (SEQ PGLV PAPTI GVLA HSDY DAPA LKQA CLLSL VVTF FFSVA WPSL and L6 LLLH LGDR ID NO: APSQS ASQP CYSL MNMT YKQG GDVE LPSGF NTSH LLVIL PDHK elbows AARP VTISC 9) LSVT LSLRP LVTV PRRP QNQL ENPG MSLD LQKK ACVL KTLE with (SEQ RASQ CTVS EACR AFIIF GPTR YNEL P (SEQ NNGT YVKV W HLCK CPT ID DISKY GVSL PAAG WV KHYQ NLGR ID NO: ATPEL LMHD (SEQ KPRK trans- NO: 1) LNWY PDYG GAVH (SEQ PYAPP REEY 3031) PTQG VAYR ID NLNV membrane QQKP VSWI TRGL ID NO: RDFA DVLD TFSN QEKD NO: SFNPE T- DGTV RQPP DFAC 3036) AYRS KRRG VSTN ENKW 3045) SFLDC ALL KLLIY RKGL D (SEQ RDPE VSYQ THVN QIHR mutation HTSR EWLG (SEQ ID NO: MGGK ETTTP LSCT VDDI insertion LHSG VIWG ID NO: 3037) PRRK STLGS KLTL QARD and S185C VPSRF SETTY 3035) NPQE TSLHP LQRK EVEG B-ALL SGSGS YNSA GLYN VSQH LQPA FLQD mutation GTDY LKSR ELQK GNEA AMYE TFPQ SLTIS LTIIK DKMA TTNIT IKVRS QLEES NLEQ DNSK EAYS ETTV IPDHY EKQR EDIAT SQVF EIGM KFTST FKGF LGGD YFCQ LKMN KGER SVITS WSEW VQSP QGNT SLQT RRGK VYGN SPSYY NCPSE LPYTF DDTAI GHDG TNSS FRTPE DVVIT GGGT YYCA LYQG VQSQ INNSS PESFG KLEIT KHYY LSTAT TSVIS GEMD RDSSL RADA YGGS KDTY TVFTT PI TCLA APTV YAMD DALH PANV (SEQ GNVS SIFPPS YWGQ MQAL STPET ID ACDA SN GTSV PPR TLKPS NO: PILSS (SEQ TVSS (SEQ LSPG 3041) SRSLD ID (SEQ ID NO: NVSD CRES NO: ID 3038) LSTTS GKNG 3033) NO: TSLAT PHVY 3034) SPTKP QDLL YTSSS LSLGT PILSDI TNSTL KAEIK PPPFS CSGIR LQSGI EVKL LTLNP TQGIC VAQG LEQN QPILT KTSSC SLGS AEFK NQEE KDRG AYVT EGLA MSSF RVLC YQNQ GEEQ (SEQ ADAD ID AGAQ NO: VCSL 3047) LLAQ SEVRP QCLL LVLA NRTEI SSKL QLMK KHQS DLKK LG (SEQ ID NO: 3039) MALP DIQM GGGG EVKL TTTPA FWVL RSKR RVKF GSGA MPRG YREG LLTISI KKRI IL7R VTAL TQTTS S.sub.4 QESG PRPPT VVVG SRLL SRSA TNFSL WTAL ANDF LSFFS KPIV with L5 LLPLA SLSAS (SEQ PGLV PAPTI GVLA HSDY DAPA LKQA CLLSL VVTF VALL WPSL and L6 LLLH LGDR ID NO: APSQS ASQP CYSL MNMT YKQG GDVE LPSGF NTSH VILAC PDHK elbows AARP VTISC 9) LSVT LSLRP LVTV PRRP QNQL ENPG MSLD LQKK VLW KTLE with (SEQ RASQ CTVS EACR AFIIF GPTR YNEL P (SEQ NNGT YVKV (SEQ HLCK S185C ID DISKY GVSL PAAG WV KHYQ NLGR ID NO: ATPEL LMHD ID KPRK B-ALL NO: 1) LNWY PDYG GAVH (SEQ PYAPP REEY 3031) PTQG VAYR NO: NLNV mutation QQKP VSWI TRGL ID NO: RDFA DVLD TFSN QEKD 3046) SFNPE only DGTV RQPP DFAC 3036) AYRS KRRG VSTN ENKW SFLDC KLLIY RKGL D (SEQ RDPE VSYQ THVN QIHR HTSR EWLG (SEQ ID NO: MGGK ETTTP LSCT VDDI LHSG VIWG ID NO: 3037) PRRK STLGS KLTL QARD VPSRF SETTY 3035) NPQE TSLHP LQRK EVEG SGSGS YNSA GLYN VSQH LQPA FLQD GTDY LKSR ELQK GNEA AMYE TFPQ SLTIS LTIIK DKMA TTNIT IKVRS QLEES NLEQ DNSK EAYS ETTV IPDHY EKQR EDIAT SQVF EIGM KFTST FKGF LGGD YFCQ LKMN KGER SVITS WSEW VQSP QGNT SLQT RRGK VYGN SPSYY NCPSE LPYTF DDTAI GHDG TNSS FRTPE DVVIT GGGT YYCA LYQG VQSQ INNSS PESFG KLEIT KHYY LSTAT TSVIS GEMD RDSSL RADA YGGS KDTY TVFTT PI TCLA APTV YAMD DALH PANV (SEQ GNVS SIFPPS YWGQ MQAL STPET ID ACDA SN GTSV PPR TLKPS NO: PILSS (SEQ TVSS (SEQ LSPG 3041) SRSLD ID (SEQ ID NO: NVSD CRES NO: ID 3038) LSTTS GKNG 3033) NO: TSLAT PHVY 3034) SPTKP QDLL YTSSS LSLGT PILSDI TNSTL KAEIK PPPFS CSGIR LQSGI EVKL LTLNP TQGIC VAQG LEQN QPILT KTSSC SLGS AEFK NQEE KDRG AYVT EGLA MSSF RVLC YQNQ GEEQ (SEQ ADAD ID AGAQ NO: VCSL 3047) LLAQ SEVRP QCLL LVLA NRTEI SSKL QLMK KHQS DLKK LG (SEQ ID NO: 3039) MALP DIQM GGGG EVKL TTTPA FWVL RSKR RVKF GSGA MPRG YREG LLTISI KKRI IL7R VTAL TQTTS S.sub.4 QESG PRPPT VVVG SRLL SRSA TNFSL WTAL ANDF LSFFS KPIV with L5 LLPLA SLSAS (SEQ PGLV PAPTI GVLA HSDY DAPA LKQA CLLSL VVTF VALL WPSL and L6 LLLH LGDR ID NO: APSQS ASQP CYSL MNMT YKQG GDVE LPSGF NTSH VILAC PDHK elbows AARP VTISC 9) LSVT LSLRP LVTV PRRP QNQL ENPG MSLD LQKK VLW KTLE WT (SEQ RASQ CTVS EACR AFIIF GPTR YNEL P (SEQ NNGT YVKV (SEQ HLCK ID DISKY GVSL PAAG WV KHYQ NLGR ID NO: ATPEL LMHD ID KPRK NO: 1) LNWY PDYG GAVH (SEQ PYAPP REEY 3031) PTQG VAYR NO: NLNV QQKP VSWI TRGL ID NO: RDFA DVLD TFSN QEKD 3046) SFNPE DGTV RQPP DFAC 3036) AYRS KRRG VSTN ENKW SFLDC KLLIY RKGL D (SEQ RDPE VSYQ THVN QIHR HTSR EWLG (SEQ ID NO: MGGK ETTTP LSSTK VDDI LHSG VIWG ID NO: 3037) PRRK STLGS LTLL QARD VPSRF SETTY 3035) NPQE TSLHP QRKL EVEG SGSGS YNSA GLYN VSQH QPAA FLQD GTDY LKSR ELQK GNEA MYEI TFPQ SLTIS LTIIK DKMA TTNIT KVRSI QLEES NLEQ DNSK EAYS ETTV PDHY EKQR EDIAT SQVF EIGM KFTST FKGF LGGD YFCQ LKMN KGER SVITS WSEW VQSP QGNT SLQT RRGK VYGN SPSYY NCPSE LPYTF DDTAI GHDG TNSS FRTPE DVVIT GGGT YYCA LYQG VQSQ INNSS PESFG KLEIT KHYY LSTAT TSVIS GEMD RDSSL RADA YGGS KDTY TVFTT PI TCLA APTV YAMD DALH PANV (SEQ GNVS SIFPPS YWGQ MQAL STPET ID ACDA SN GTSV PPR TLKPS NO: PILSS (SEQ TVSS (SEQ LSPG 3040) SRSLD ID (SEQ ID NO: NVSD CRES NO: ID 3038) LSTTS GKNG 3033) NO: TSLAT PHVY 3034) SPTKP QDLL YTSSS LSLGT PILSDI TNSTL KAEIK PPPFS CSGIR LQSGI

EVKL LTLNP TQGIC VAQG LEQN QPILT KTSSC SLGS AEFK NQEE KDRG AYVT EGLA MSSF RVLC YQNQ GEEQ (SEQ ADAD ID AGAQ NO: VCSL 3047) LLAQ SEVRP QCLL LVLA NRTEI SSKL QLMK KHQS DLKK LG (SEQ ID NO: 3039) MALP DIQM GGGG EVKL TTTPA FWVL RSKR RVKF GSGA MPRG VNLS LLTCP KKRI IL7R VTAL TQTTS S.sub.4 QESG PRPPT VVVG SRLL SRSA TNFSL WTAL STKLT TISILS KPIV with L6 LLPLA SLSAS (SEQ PGLV PAPTI GVLA HSDY DAPA LKQA CLLSL LLQR FFSVA WPSL elbow LLLH LGDR ID NO: APSQS ASQP CYSL MNMT YKQG GDVE LPSGF KLQP LLVIL PDHK only AARP VTISC 9) LSVT LSLRP LVTV PRRP QNQL ENPG MSLD AAMY ACVL KTLE with (SEQ RASQ CTVS EACR AFIIF GPTR YNEL P (SEQ NNGT EIKVR W HLCK CPT ID DISKY GVSL PAAG WV KHYQ NLGR ID NO: ATPEL SIPDH (SEQ KPRK trans- NO: 1) LNWY PDYG GAVH (SEQ PYAPP REEY 3031) PTQG YFKG ID NLNV membrane QQKP VSWI TRGL ID NO: RDFA DVLD TFSN FWSE NO: SFNPE T- DGTV RQPP DFAC 3036) AYRS KRRG VSTN WSPS 3045) SFLDC ALL KLLIY RKGL D (SEQ RDPE VSYQ YYFR QIHR mutation HTSR EWLG (SEQ ID NO: MGGK ETTTP TPEIN VDDI insertion LHSG VIWG ID NO: 3037) PRRK STLGS NSSG QARD only VPSRF SETTY 3035) NPQE TSLHP EMDPI EVEG SGSGS YNSA GLYN VSQH (SEQ FLQD GTDY LKSR ELQK GNEA ID TFPQ SLTIS LTIIK DKMA TTNIT NO: QLEES NLEQ DNSK EAYS ETTV 3042) EKQR EDIAT SQVF EIGM KFTST LGGD YFCQ LKMN KGER SVITS VQSP QGNT SLQT RRGK VYGN NCPSE LPYTF DDTAI GHDG TNSS DVVIT GGGT YYCA LYQG VQSQ PESFG KLEIT KHYY LSTAT TSVIS RDSSL RADA YGGS KDTY TVFTT TCLA APTV YAMD DALH PANV GNVS SIFPPS YWGQ MQAL STPET ACDA SN GTSV PPR TLKPS PILSS (SEQ TVSS (SEQ LSPG SRSLD ID (SEQ ID NO: NVSD CRES NO: ID 3038) LSTTS GKNG 3033) NO: TSLAT PHVY 3034) SPTKP QDLL YTSSS LSLGT PILSDI TNSTL KAEIK PPPFS CSGIR LQSGI EVKL LTLNP TQGIC VAQG LEQN QPILT KTSSC SLGS AEFK NQEE KDRG AYVT EGLA MSSF RVLC YQNQ GEEQ (SEQ ADAD ID AGAQ NO: VCSL 3047) LLAQ SEVRP QCLL LVLA NRTEI SSKL QLMK KHQS DLKK LG (SEQ ID NO: 3039) MALP DIQM GGGG EVKL TTTPA FWVL RSKR RVKF GSGA MPRG VNLS LLTCP KKRI IL7R VTAL TQTTS S.sub.4 QESG PRPPT VVVG SRLL SRSA TNFSL WTAL CTKL TISILS KPIV with L6 LLPLA SLSAS (SEQ PGLV PAPTI GVLA HSDY DAPA LKQA CLLSL TLLQ FFSVA WPSL elbows LLLH LGDR ID NO: APSQS ASQP CYSL MNMT YKQG GDVE LPSGF RKLQ LLVIL PDHK with AARP VTISC 9) LSVT LSLRP LVTV PRRP QNQL ENPG MSLD PAAM ACVL KTLE CPT (SEQ RASQ CTVS EACR AFIIF GPTR YNEL P (SEQ NNGT YEIKV W HLCK trans- ID DISKY GVSL PAAG WV KHYQ NLGR ID NO: ATPEL RSIPD (SEQ KPRK membrane NO: 1) LNWY PDYG GAVH (SEQ PYAPP REEY 3031) PTQG HYFK ID NLNV T- QQKP VSWI TRGL ID NO: RDFA DVLD TFSN GFWS NO: SFNPE ALL DGTV RQPP DFAC 3036) AYRS KRRG VSTN EWSP 3045) SFLDC mutation KLLIY RKGL D (SEQ RDPE VSYQ SYYF QIHR insertion HTSR EWLG (SEQ ID NO: MGGK ETTTP RTPEI VDDI and S185C LHSG VIWG ID NO: 3037) PRRK STLGS NNSS QARD B-ALL VPSRF SETTY 3035) NPQE TSLHP GEMD EVEG mutation SGSGS YNSA GLYN VSQH PI FLQD GTDY LKSR ELQK GNEA (SEQ TFPQ SLTIS LTIIK DKMA TTNIT ID QLEES NLEQ DNSK EAYS ETTV NO: EKQR EDIAT SQVF EIGM KFTST 3043) LGGD YFCQ LKMN KGER SVITS VQSP QGNT SLQT RRGK VYGN NCPSE LPYTF DDTAI GHDG TNSS DVVIT GGGT YYCA LYQG VQSQ PESFG KLEIT KHYY LSTAT TSVIS RDSSL RADA YGGS KDTY TVFTT TCLA APTV YAMD DALH PANV GNVS SIFPPS YWGQ MQAL STPET ACDA SN GTSV PPR TLKPS PILSS (SEQ TVSS (SEQ LSPG SRSLD ID (SEQ ID NO: NVSD CRES NO: ID 3038) LSTTS GKNG 3033) NO: TSLAT PHVY 3034) SPTKP QDLL YTSSS LSLGT PILSDI TNSTL KAEIK PPPFS CSGIR LQSGI EVKL LTLNP TQGIC VAQG LEQN QPILT KTSSC SLGS AEFK NQEE KDRG AYVT EGLA MSSF RVLC YQNQ GEEQ (SEQ ADAD ID AGAQ NO: VCSL 3047) LLAQ SEVRP QCLL LVLA NRTEI SSKL QLMK KHQS DLKK LG (SEQ ID NO: 3039) MALP DIQM GGGG EVKL TTTPA FWVL RSKR RVKF GSGA MPRG VNLS LLTISI KKRI IL7R VTAL TQTTS S.sub.4 QESG PRPPT VVVG SRLL SRSA TNFSL WTAL CTKL LSFFS KPIV with L6 LLPLA SLSAS (SEQ PGLV PAPTI GVLA HSDY DAPA LKQA CLLSL TLLQ VALL WPSL elbows LLLH LGDR ID NO: APSQS ASQP CYSL MNMT YKQG GDVE LPSGF RKLQ VILAC PDHK with AARP VTISC 9) LSVT LSLRP LVTV PRRP QNQL ENPG MSLD PAAM VLW KTLE S185C (SEQ RASQ CTVS EACR AFIIF GPTR YNEL P (SEQ NNGT YEIKV (SEQ HLCK B-ALL ID DISKY GVSL PAAG WV KHYQ NLGR ID NO: ATPEL RSIPD ID KPRK mutation NO: 1) LNWY PDYG GAVH (SEQ PYAPP REEY 3031) PTQG HYFK NO: NLNV only QQKP VSWI TRGL ID NO: RDFA DVLD TFSN GFWS 3046) SFNPE DGTV RQPP DFAC 3036) AYRS KRRG VSTN EWSP SFLDC KLLIY RKGL D (SEQ RDPE VSYQ SYYF QIHR HTSR EWLG (SEQ ID NO: MGGK ETTTP RTPEI VDDI LHSG VIWG ID NO: 3037) PRRK STLGS NNSS QARD VPSRF SETTY 3035) NPQE TSLHP GEMD EVEG SGSGS YNSA GLYN VSQH PI FLQD GTDY LKSR ELQK GNEA (SEQ TFPQ SLTIS LTIIK DKMA TTNIT ID QLEES NLEQ DNSK EAYS ETTV NO: EKQR EDIAT SQVF EIGM KFTST 3043) LGGD YFCQ LKMN KGER SVITS VQSP QGNT SLQT RRGK VYGN NCPSE LPYTF DDTAI GHDG TNSS DVVIT GGGT YYCA LYQG VQSQ PESFG KLEIT KHYY LSTAT TSVIS RDSSL RADA YGGS KDTY TVFTT TCLA APTV YAMD DALH PANV GNVS SIFPPS YWGQ MQAL STPET ACDA SN GTSV PPR TLKPS PILSS (SEQ TVSS (SEQ LSPG SRSLD ID (SEQ ID NO: NVSD CRES NO: ID 3038) LSTTS GKNG 3033) NO: TSLAT PHVY 3034) SPTKP QDLL YTSSS LSLGT PILSDI TNSTL KAEIK PPPFS CSGIR LQSGI EVKL LTLNP TQGIC VAQG LEQN QPILT KTSSC SLGS AEFK NQEE KDRG AYVT EGLA MSSF RVLC YQNQ GEEQ (SEQ ADAD ID AGAQ NO: VCSL 3047) LLAQ SEVRP QCLL LVLA NRTEI SSKL QLMK KHQS DLKK LG (SEQ ID NO: 3039) MALP DIQM GGGG EVKL TTTPA FWVL RSKR RVKF GSGA MPRG VNLS LLTISI KKRI IL7R VTAL TQTTS S.sub.4 QESG PRPPT VVVG SRLL SRSA TNFSL WTAL STKLT LSFFS KPIV with L6 LLPLA SLSAS (SEQ PGLV PAPTI GVLA HSDY DAPA LKQA CLLSL LLQR VALL WPSL elbows LLLH LGDR ID NO: APSQS ASQP CYSL MNMT YKQG GDVE LPSGF KLQP VILAC PDHK WT AARP VTISC 9) LSVT LSLRP LVTV PRRP QNQL ENPG MSLD AAMY VLW KTLE (SEQ RASQ CTVS EACR AFIIF GPTR YNEL P (SEQ NNGT EIKVR (SEQ HLCK ID DISKY GVSL PAAG WV KHYQ NLGR ID NO: ATPEL SIPDH ID KPRK NO: 1) LNWY PDYG GAVH (SEQ PYAPP REEY 3031) PTQG YFKG NO: NLNV QQKP VSWI TRGL ID NO: RDFA DVLD TFSN FWSE 3046) SFNPE DGTV RQPP DFAC 3036) AYRS KRRG VSTN WSPS SFLDC KLLIY RKGL D (SEQ RDPE VSYQ YYFR QIHR HTSR EWLG (SEQ ID NO: MGGK ETTTP TPEIN VDDI LHSG VIWG ID NO: 3037) PRRK STLGS NSSG QARD VPSRF SETTY 3035) NPQE TSLHP EMDPI EVEG SGSGS YNSA GLYN VSQH (SEQ FLQD GTDY LKSR ELQK GNEA ID TFPQ SLTIS LTIIK DKMA TTNIT NO: QLEES NLEQ DNSK EAYS ETTV 3042) EKQR EDIAT SQVF EIGM KFTST LGGD YFCQ LKMN KGER SVITS VQSP QGNT SLQT RRGK VYGN NCPSE

LPYTF DDTAI GHDG TNSS DVVIT GGGT YYCA LYQG VQSQ PESFG KLEIT KHYY LSTAT TSVIS RDSSL RADA YGGS KDTY TVFTT TCLA APTV YAMD DALH PANV GNVS SIFPPS YWGQ MQAL STPET ACDA SN GTSV PPR TLKPS PILSS (SEQ TVSS (SEQ LSPG SRSLD ID (SEQ ID NO: NVSD CRES NO: ID 3038) LSTTS GKNG 3033) NO: TSLAT PHVY 3034) SPTKP QDLL YTSSS LSLGT PILSDI TNSTL KAEIK PPPFS CSGIR LQSGI EVKL LTLNP TQGIC VAQG LEQN QPILT KTSSC SLGS AEFK NQEE KDRG AYVT EGLA MSSF RVLC YQNQ GEEQ (SEQ ADAD ID AGAQ NO: VCSL 3047) LLAQ SEVRP QCLL LVLA NRTEI SSKL QLMK KHQS DLKK LG (SEQ ID NO: 3039) MALP DIQM GGGG EVKL TTTPA FWVL RSKR RVKF GSGA MPRG PEINN LLTCP KKRI IL-7R VTAL TQTTS S.sub.4 QESG PRPPT VVVG SRLL SRSA TNFSL WTAL SSGE TISILS KPIV with LLPLA SLSAS (SEQ PGLV PAPTI GVLA HSDY DAPA LKQA CLLSL MDPI FFSVA WPSL CPT T LLLH LGDR ID NO: APSQS ASQP CYSL MNMT YKQG GDVE LPSGF (SEQ LLVIL PDHK ALL AARP VTISC 9) LSVT LSLRP LVTV PRRP QNQL ENPG MSLD ID ACVL KTLE mutation (SEQ RASQ CTVS EACR AFIIF GPTR YNEL P (SEQ NNGT NO: W HLCK Lacking ID DISKY GVSL PAAG WV KHYQ NLGR ID NO: ATPEL 3044) (SEQ KPRK elbows NO: 1) LNWY PDYG GAVH (SEQ PYAPP REEY 3031) PTQG ID NLNV and QQKP VSWI TRGL ID NO: RDFA DVLD TFSN NO: SFNPE WSEW DGTV RQPP DFAC 3036) AYRS KRRG VSTN 3045) SFLDC S (SEQ KLLIY RKGL D (SEQ RDPE VSYQ QIHR ID NO: HTSR EWLG (SEQ ID NO: MGGK ETTTP VDDI 3070) LHSG VIWG ID NO: 3037) PRRK STLGS QARD motif VPSRF SETTY 3035) NPQE TSLHP EVEG (sugar SGSGS YNSA GLYN VSQH FLQD bridge) GTDY LKSR ELQK GNEA TFPQ SLTIS LTIIK DKMA TTNIT QLEES NLEQ DNSK EAYS ETTV EKQR EDIAT SQVF EIGM KFTST LGGD YFCQ LKMN KGER SVITS VQSP QGNT SLQT RRGK VYGN NCPSE LPYTF DDTAI GHDG TNSS DVVIT GGGT YYCA LYQG VQSQ PESFG KLEIT KHYY LSTAT TSVIS RDSSL RADA YGGS KDTY TVFTT TCLA APTV YAMD DALH PANV GNVS SIFPPS YWGQ MQAL STPET ACDA SN GTSV PPR TLKPS PILSS (SEQ TVSS (SEQ LSPG SRSLD ID (SEQ ID NO: NVSD CRES NO: ID 3038) LSTTS GKNG 3033) NO: TSLAT PHVY 3034) SPTKP QDLL YTSSS LSLGT PILSDI TNSTL KAEIK PPPFS CSGIR LQSGI EVKL LTLNP TQGIC VAQG LEQN QPILT KTSSC SLGS AEFK NQEE KDRG AYVT EGLA MSSF RVLC YQNQ GEEQ (SEQ ADAD ID AGAQ NO: VCSL 3047) LLAQ SEVRP QCLL LVLA NRTEI SSKL QLMK KHQS DLKK LG (SEQ ID NO: 3039)

Protocol--Nucleofection Using Nucleofector 4D:

[0435] Perform nucleofection protocol as described above (Example 6), using 20 .mu.g of each gRNA (gGM-CSF and gCD3.epsilon.) to each tube of 15 .mu.g Cas9 mRNA.

[0436] Step 4: Assessment of CRISPR Activity and Td Efficiency (Day 10)

[0437] Take 5.times.10.sup.5 cells from each sample and analyze by flow cytometry. Wash samples with RB. Add 5 .mu.l of CD3 APC and 2 .mu.l of anti-FAB BV421 (detects CAR transduction). Wash. Perform Flow cytometry. Cells should be CD3.epsilon.-negative, CD34-positive and FAB+. Harvest T cells (Day 11).

[0438] Purification of CAR-T cells. TCR negative cells can be purified using TCRa/b negative selection to remove TCR positive cells.

[0439] Step 5: Assessment of CAR-T Activity In Vivo

[0440] Inject 5.times.10.sup.6 CAR-T per mouse I.V. Assess serum cytokine levels (Day +1, +2, +3 +4, +5, +10, +15). Measure serum cytokine levels using Luminex multiplex cytokine profiling assay to check for elevations in CRS related cytokines. Perform a 4-hr chromium release assay against targets cells (Raji) to assess in vitro activity (Day 11). Monitor efficacy of tumor clearance using flow cytometry of blood to detect hCD45, CD19+ cells.

[0441] A modified gRNA protocol for T cell CRISPR and CAR-T transduction of UCART19 is provided below.

[0442] Day 0--T Cell Activation:

[0443] Purify T cells from a leukapheresis chamber using a Miltenyi human PanT isolation kit. Resuspend in media. Count cells. Determine the number of human T cell activation CD3/CD28 beads required to obtain a 3:1 bead:cell ratio. Wash beads 2.times. with T cell media. Dilute cells at 1.256 cells/mL in hXcyte media. Add human T cell activation CD3/CD28 beads

[0444] T cells may then be transduced with one or more CARs targeted to (i.e., that recognizes) one or more targets, for example with a lentivirus containing a CAR construct. Any other suitable method of transduction may be used.

[0445] Day 2: 4.times.10.sup.6 cells per reaction are used. EO-115--100 .mu.l transfection volume is programmed, and the entire supplement added to the Nucleofector.TM. Solution P3. Cell culture plates are prepared by filling appropriate number of wells with desired volume of recommended culture media (2 ml in 6 well plate) and pre-incubating/equilibrating plates in a humidified 37.degree. C./5% CO.sub.2 incubator. Beads are magnetically removed (twice to ensure complete removal), then cells counted and cell density determined. The required number of cells are centrifuged at 90.times.g for 10 minutes at room temperature, the supernatant removed completely. Cells are then resuspended in PBS (1 ml) and transferred to a microcentrifuge tube, and the required number of cells centrifuged at 90.times.g for 10 minutes at room temperature. The supernatant is removed completely, and the cell pellet resuspended carefully in complete room temperature 4D Nucleofector.TM. Solution P3, 4.times.10.sup.6 per 100 .mu.l). Twenty .mu.g of gRNA (gGM-CSF and gTRAC) are added to each tube of 15 .mu.g Cas9 mRNA. Then 100 .mu.l of cells is added to each tube of Cas9/gRNA, gently mixed and everything transferred into the Nucleocuvette.TM.. The cuvette is gently tapped to remove bubbles. Electroporation is carried out using program (Human T cell stim EO-115). After run completion, the NucleocuvetteTM is carefully removed from the vessel from the retainer using a specialized tool. Cells are resuspended with pre-warmed medium. The media is then taken up from destination well, added to cuvette, and gently pipetted up and down two to three times. This is then transferred to well. This procedure is repeated with media from same well and incubated at 37.degree. C.

[0446] Day 5: Assessment of CRISPR activity and Td efficiency. Samples of cells may then be assessed for transduction efficiency by taking a 5.times.10.sup.5 cells from each sample and analyzing by flow cytometry. Samples are fix permeablised and anlaysed by FACS for CD3, CD34 and intracellular GM-CSF.

[0447] Assessment of Genetic Deletion.

[0448] To assess genetic deletion of GM-CSF and TRAC, 5.times.10.sup.5 cells are harvested from each sample and their DNA extracted. Gene editing efficiency is assessed using target sequencing of the target loci using TIDE-analysis or deep sequencing.

[0449] Day 11

[0450] Bleed mice and measure tumor burden.

[0451] CD3 deplete T cells and inject into mice.

[0452] Inject mice with 5.times.10.sup.6 CAR+ T cells/mouse.

[0453] Mouse groups are provided in Table 20 below:

[0454] Mice are then bled on days 0, 1, 2, 3, 5, 7, 14, and 21 for FACS and plasma measurements, weighed, and body temperature is determined.

[0455] The panel for detecting specific markers of the CAR-T cells is as follows:

TABLE-US-00025 TABLE 20 Sample Gene T cell ID editing Tumor source CAR-T CAR-T A -- 2 .times. 10.sup.6/mouse -- -- B TRAC 2 .times. 10.sup.6/mouse PanT CAR19 + 5 .times. 10.sup.6/ CD34 mouse C TRAC + 2 .times. 10.sup.6/mouse PanT CAR19 CD34 5 .times. 10.sup.6/ GM-CSF mouse D TRAC 2 .times. 10.sup.6/mouse PanT CAR19 + 5 .times. 10.sup.6/ IL7r + CD34 mouse E TRAC + 2 .times. 10.sup.6/mouse PanT CAR19 + 5 .times. 10.sup.6/ GM-CSF IL7r + CD34 mouse Attune-CAR-T in vivo panel-CRS Titer 50 .mu.l blood Bandpass or 500K Detector (nm) Antigen Colour Product # in 100 .mu.l BL1 530/30 BL2 695/40 7aad 7AAd 1 ul RL1 670/14 CD19 APC BD555415 2 ul RL2 720/30 RL3 780/60 CD4 APC-H7 BD560158 1 ul VL1 450/40 mCD45 BV421 BD 563890 1 ul VL2 525/50 CD8 BV510 BD563256 4 ul VL3 610/20 VL4 660/20 CD3 BV650 BD 563852 2 ul VL5 710/50 VL6 780/60 hCD45 BV785 BD 563716 1 ul YL1 585/16 CD34 PE BD Pool PE 2 ul YL2 620/15 YL3 780/60

[0456] Cytokine analysis and assessment of CRS is assed using Millipore luminex multiplex cytokine analysis.

[0457] Sequences for preparation of a vector as described herein include, but are not limited to, the following:

TABLE-US-00026 -Left ITR of vector for insertion of CD34 into GM-CSF locus SEQ ID NO: 3048 CCTGCAGGCAGCTGCGCGCTCGCTCGCTCACTGAGGCCGCCCGGGCGTCGGGCGACCTTTGGTCGCCCGGCCTC- AGTGAGCGAGC GAGCGCGCAGAGAGGGAGTGGCCAACTCCATCACTAGGGGTTCCT -Left Homology Arm of vector for insertion of CD34 into GM-CSF locus SEQ ID NO: 3049 cctgagatggatgcagccacagccctggagccagcctgaagctcctggtgtcttctgggggctacatataggag- tgtagtccgaacctcagaggggcaaacctgctctgcagagggaatcaaggttcacataacc agagaggggagtcactcaggaaggtggctccagagccaagagtcagactctgggtcccgacttgacccagccac- accccctctgaagcttgctgagagtggctgcagtctcgctgctggatgtgcacatggtggt cattccctctgctcacaggggcaggggtcccccottactggactgaggttgccccctgctccaggtcctgggtg- ggagcccatgtgaactgtcagtggggcaggtctgtgagagctcccctcacactcaagtctctc acagtggccagagaagaggaaggctggagtcagaatgaggcaccagggcgggcatagcctgcccaaaggcccct- gggattacaggcaggatggggagccctatctaagtgtctcccacgccccaccccagc cattccaggccaggaagtccaaactgtgcccctcagagggagggggcagcctcaggcccattcagactgcccag- ggagggctggagagccctcaggaaggcgggtgggtgggctgtcggttcttggaaaggt tcattaatgaaaacccccaagcctgaccacctagggaaaaggctcaccgttcccatgtgtggctgataagggcc- aggagattccacagttcaggtagttcccccgcctccctggcattttgtggtcaccattaatcattt cctctgtgtatttaagagctatttgccagtgagcccaGTACACAGAGAGAAAGGCTAAAGTTCTCTGGAGGATG- TGGCTGCAGAGCCTGCTGCTCTTGG GCACTGTGGCCTGCAGCATCTCTGCACCCGCCCGCTCGCCCAGCCCCAGCACGCAGCCCTGGGAGCATGTGAAT- GCCATCCAGGA GGCCC -EFS promotor of vector for insertion of CD34 into GM-CSF locus SEQ ID NO: 3050 GGCTCCGGTGCCCGTCAGTGGGCAGAGCGCACATCGCCCACAGTCCCCGAGAAGTTGGGGGGAGGGGTCGGCAA- TTGATCCGGT GCCTAGAGAAGGTGGCGCGGGGTAAACTGGGAAAGTGATGTCGTGTACTGGCTCCGCCTTTTTCCCGAGGGTGG- GGGAGAACCG TATATAAGTGCAGTAGTCGCCGTGAACGTTCTTTTTCGCAACGGGTTTGCCGCCAGAACACAGG -trCD34 of vector for insertion of CD34 into GM-CSF locus SEQ ID NO: 3051 atgccgcggggctggaccgcgctttgcttgctgagtttgctgccttctgggttcatgagtcttgacaacaacgg- tactgctaccccagagttacctacccagggaacattttcaaatgtttctacaaatgtatcctaccaa gaaactacaacacctagtaccottggaagtaccagcctgcaccctgtgtctcaacatggcaatgaggccacaac- aaacatcacagaaacgacagtcaaattcacatctacctctgtgataacctcagtttatggaaac acaaactatctgtccagtcacagacctctgtaatcagcacagtgttcaccaccccagccaacgtttcaactcca- gagacaaccttgaagcctagcctgtcacctggaaatgtttcagacctttcaaccactagcactag ccttgcaacatctcccactaaaccctatacatcatcttctcctatcctaagtgacatcaaggcagaaatcaaat- gttcaggcatcagagaagtgaaattgactcagggcatctgcctggagcaaaataagacctccagct gtgcggagtttaagaaggacaggggagagggcctggcccgagtgctgtgtggggaggagcaggctgatgctgat- gctggggcccaggtatgctccctgctccttgcccagtctgaggtgaggcctcagtgtcta ctgctggtcttggccaacagaacagaaatttccagcaaactccaacttatgaaaaagcaccaatctgacctgaa- aaagctggggatcctagatttcactgagcaagatgttgcaagccaccagagctattcccaaaag accctgattgcactggtcacctcgggagccctgctggctgtcttgggcatcactggctatttcctgatgaatcg- ccgcagctggagccccatttaa -hGMB Poly A of vector for insertion of CD34 into GM-CSF locus SEQ ID NO: 3052 ACGGGTGGCATCCCTGTGACCCCTCCCCAGTGCCTCTCCTGGCCCTGGAAGTTGCCACTCCAGTGCCCACCAGC- CTTGTCCTAATA AAATTAAGTTGCATCATTTTGTCTGACTAGGTGTCCTTCTATAATATTATGGGGTGGAGGGGGGTGGTATGGAG- CAAGGGGCAAG TTGGGAAGACAACCTGTAGGGCCTGCGGGGTCTATTGGGAACCAAGCTGGAGTGCAGTGGCACAATCTTGGCTC- ACTGCAATCT CCGCCTCCTGGGTTCAAGCGATTCTCCTGCCTCAGCCTCCCGAGTTGTTGGGATTCCAGGCATGCATGACCAGG- CTCAGCTAATTT TTGTTTTTTTGGTAGAGACGGGGTTTCACCATATTGGCCAGGCTGGTCTCCAACTCCTAATCTCAGGTGATCTA- CCCACCTTGGCC TCCCAAATTGCTGGGATTACAGGCGTGAACCACTGCTCCCTTCCCTGTCCTTCTGATTTTGTAGGTAACCACGT- GCGGACCGA -RHA of vector for insertion of CD34 into GM-CSF locus SEQ ID NO: 3053 CGTCTCCTGAACCTGAGTAGAGACACTGCTGCTGAGATGgtaagtgagagaatgtgggcctgtgcctaggccac- ccagctggcccctgactggccacgcctgtcagcttgat aacatgacattttccttttctacagAATGAAACAGTAGAAGTCATCTCAGAAATGTTTGACCTCCAGgtaagat- gcttctctctgacatagctttccagaagcccctgccctggg gtggaggtggggactccattttagatggcaccacacagggttgtccactttctctccagtcagctggctgcagg- aggagggggtagcaactgg gtgctcaagaggctgctggccgtgccectatggcagtcacatgagctcctttatcagctgageggccatgggca- gacctagcattcaatggccaggagtcaccaggggacaggtggtaaagtgggggtcacttca tgagacaggagctgtgggtttggggcgctcactgtgccccgagaccaagtcctgttgagacagtgctgactaca- gagaggcacagaggggtttcaggaacaacccttgcccacccagcaggtccaggtgaggc cccaccccectctccctgaatgatggggtgagagtcacctccttccctaaggctgggctcctctccaggtgccg- ctgagggtggcctgggcggggcagtgagaagggcaggttcgtgcctgccatggacagggc agggtctatgactggacccagcctgtgcccctcccaagccctactcctgggggctgggggcagcagcaaaaagg- agtggtggagagttcttgtaccactgtgggcacttggccactgctcaccgacgaacgacat tttccacagGAGCCGACCTGCCTACAGACCCGCCTGGAGCTGTACAAGCAGGGCCTGCGGGGCAGCCTCACCAA- GCTCAAGGGCCCCT TGACCATGATGGCCAGCCACTACAAGCAGCACTGCCCTCCAACCCCGgtgagtgc -Right ITR of vector for insertion of CD34 into GM-CSF locus SEQ ID NO: 51 AGGAACCCCTAGTGATGGAGTTGGCCACTCCCTCTCTGCGCGCTCGCTCGCTCACTGAGGCCGGGCGACCAAAG- GTCGCCCGACG CCCGGGCTTTGCCCGGGCGGCCTCAGTGAGCGAGCGAGCGCGCAGCTGCCTGCAGG -Complete sequence of vector for insertion of CD34 into GM-CSF locus SEQ ID NO: 3054 CCTGCAGGCAGCTGCGCGCTCGCTCGCTCACTGAGGCCGCCCGGGCGTCGGGCGACCTTTGGTCGCCCGGCCTC- AGTGAGCGAGC GAGCGCGCAGAGAGGGAGTGGCCAACTCCATCACTAGGGGTTCCTcctgagatggatgcagccacagccctgga- gccagcctgaagctcctggtgtcttctgggggct acatataggagtgtagtccgaacctcagaggggcaaacctgctctgcagagggaatcaaggttcacataaccag- agaggggagtcactcaggaaggtggctccagagccaagagtcagactctgggtcccgact tgacccagccacaccccctctgaagcttgctgagagtggctgcagtctcgctgctggatgtgcacatggtggtc- attccctctgctcacaggggcaggggtccccccttactggactgaggttgccccctgctccag gtcctgggtgggagcccatgtgaactgtcagtggggcaggtctgtgagagctcccctcacactcaagtctctca- cagtggccagagaagaggaaggctggagtcagaatgaggcaccagggcgggcatagcct gcccaaaggcccctgggattacaggcaggatggggagccctat ctaagtgtctcccacgccccaccccagccattccaggccaggaagtccaaactgtgcccctcagagggaggggg- cagcctcaggcccattcagactgcccagggagggctggagagccctcaggaaggcgg gtgggtgggctgtcggttcttggaaaggttcattaatgaaaacccccaagcctgaccacctagggaaaaggctc- accgttcccatgtgtggctgataagggccaggagattccacagttcaggtagttcccccgcct ccctggcattttgtggtcaccattaatcatttcctctgtgtatttaagagctcttttgccagtgagcccaGTAC- ACAGAGAGAAAGGCTAAAGTTCTCTGGAGGATGTGGCTGC AGAGCCTGCTGCTCTTGGGCACTGTGGCCTGCAGCATCTCTGCACCCGCCCGCTCGCCCAGCCCCAGCACGCAG- CCCTGGGAGCA TGTGAATGCCATCCAGGAGGCCCGGCTCCGGTGCCCGTCAGTGGGCAGAGCGCACATCGCCCACAGTCCCCGAG- AAGTTGGGGG GAGGGGTCGGCAATTGATCCGGTGCCTAGAGAAGGTGGCGCGGGGTAAACTGGGAAAGTGATGTCGTGTACTGG- CTCCGCCTTT TTCCCGAGGGTGGGGGAGAACCGTATATAAGTGCAGTAGTCGCCGTGAACGTTCTTTTTCGCAACGGGTTTGCC- GCCAGAACACA GGatgccgcggggctggaccgcgctttgcttgctgagtttgctgccttctgggttcatgagtcttgacaacaac- ggtactgctaccccagagttacctacccagggaacattttcaaatgtttctacaaatgtatcctac caagaaactacaacacctagtacccttggaagtaccagcctgcaccctgtgtctcaacatggcaatgaggccac- aacaaacatcacagaaacgacagtcaaattcacatctacctctgtgataacctcagtttatgga aacacaaactcttctgtccagtcacagacctctgtaatcagcacagtgttcaccaccccagccaacgtttcaac- tccagagacaaccttgaagcctagcctgtcacctggaaatgtttcagacctttcaaccactagcac tagccttgcaacatctcccactaaaccctatacatcatcttctcctatcctaagtgacatcaaggcagaaatca- aatgttcaggcatcagagaagtgaaattgactcagggcatctgcctggagcaaaataagacctcca gctgtgcggagtttaagaaggacaggggagagggcctggcccgagtgctgtgtggggaggagcaggctgatgct- gatgctggggcccaggtatgctccctgctccttgcccagtctgaggtgaggcctcagtgt ctactgctggtcttggccaacagaacagaaatttccagcaaactccaacttatgaaaaagcaccaatctgacct- gaaaaagctggggatcctagatttcactgagcaagatgttgcaagccaccagagctattcccaa aagaccctgattgcactggtcacctcgggagccctgctggctgtcttgggcatcactggctatttcctgatgaa- tcgccgcagctggagccccatttaaACGGGTGGCATCCCTGTGACCCCT CCCCAGTGCCTCTCCTGGCCCTGGAAGTTGCCACTCCAGTGCCCACCAGCCTTGTCCTAATAAAATTAAGTTGC- ATCATTTTGTCT GACTAGGTGTCCTTCTATAATATTATGGGGTGGAGGGGGGTGGTATGGAGCAAGGGGCAAGTTGGGAAGACAAC- CTGTAGGGCC TGCGGGGTCTATTGGGAACCAAGCTGGAGTGCAGTGGCACAATCTTGGCTCACTGCAATCTCCGCCTCCTGGGT- TCAAGCGATTC TCCTGCCTCAGCCTCCCGAGTTGTTGGGATTCCAGGCATGCATGACCAGGCTCAGCTAATTTTTGTTTTTTTGG- TAGAGACGGGGT TTCACCATATTGGCCAGGCTGGTCTCCAACTCCTAATCTCAGGTGATCTACCCACCTTGGCCTCCCAAATTGCT- GGGATTACAGGC GTGAACCACTGCTCCCTTCCCTGTCCTTCTGATTTTGTAGGTAACCACGTGCGGACCGACGTCTCCTGAACCTG- AGTAGAGACACT GCTGCTGAGATGgtaagtgagagaatgtgggcctgtgcctaggccacccagctggcccctgactggccacgcct- gtcagcttgataacatgacattttccttttctacagAATGAAACAGTAG AAGTCATCTCAGAAATGTTTGACCTCCAGgtaagatgatctctctgacatagattccagaagcccctgccctgg- ggtggaggtggggactccattttagatggcaccacacagggttgt ccactttctctccagtcagctggctgcaggaggagggggtagcaactgggtgctcaagaggctgctggccgtgc- ccctatggcagtcacatgagctcctttatcagctgagcggccatgggcagacctagcattca atggccaggagtcaccaggggacaggtggtaaagtgggggtcacttcatgagacaggagctgtgggtttggggc- gctcactgtgccccgagaccaagtcctgttgagacagtgctgactacagagaggcacag aggggtttcaggaacaacccttgcccacccagcaggtccaggtgaggccccacccccctctccctgaatgatgg- ggtgagagtcacctccttccctaaggctgggctcctctccaggtgccgctgagggtggcct gggcggggcagtgagaagggcaggttcgtgcctgccatggacagggcagggtctatgactggacccagcctgtg- cccctcccaagccctactcctgggggctgggggcagcagcaaaaaggagtggtggag agttcttgtaccactgtgggcacttggccactgctcaccgacgaacgacattttccacagGAGCCGACCTGCCT- ACAGACCCGCCTGGAGCTGTACAAGCAGGGCCTG CGGGGCAGCCTCACCAAGCTCAAGGGCCCCTTGACCATGATGGCCAGCCACTACAAGCAGCACTGCCCTCCAAC- CCCGgtgagtgcA GGAACCCCTAGTGATGGAGTTGGCCACTCCCTCTCTGCGCGCTCGCTCGCTCACTGAGGCCGGGCGACCAAAGG- TCGCCCGACGC CCGGGCTTTGCCCGGGCGGCCTCAGTGAGCGAGCG AGCGCGCAGCTGCCTGCAGG -left ITR of donor construct for inserting GFP into CD3 locus SEQ ID NO: 3048 CCTGCAGGCAGCTGCGCGCTCGCTCGCTCACTGAGGCCGCCCGGGCGTCGGGCGACCTTTGGTCGCCCGGCCTC- AGTGAGCGAGC GAGCGCGCAGAGAGGGAGTGGCCAACTCCATCACTAGGGGTTCCT -cloning remnants of donor construct for inserting GFP into CD3 locus SEQ ID NO: 3055 GCGGCCGCATCGATTGaattc -CD3 L homology arm of donor construct for inserting GFP into CD3 locus SEQ ID NO: 3056 AGGTAAGTCCACGAATCAGTGATTCAGTGGTGTGGAGAGCTTTATTTCTGAGAAGGCCAGTAGCGCTCCCTTCT- GACAAGCAAAT CTAAGACCTGGATGACAGATGACTTCCTGCATTTGGTTGGTTCTTTTGTCATTCATATCTATCTGTAATACAGT-

TCTGGCTAATTTA AGAGGATAAGCTTGAAGACCTCTGGAATTTTTCGGCTTTAGGACTTTAAGGCTTTCTGAGCTTCAGTAGATCTA- GATCTAGGAGC TCATGCTGGTATATTCTGAATCCGATGTATCTGAGTTACATCTATGAGCTACTTAATAAATATATCTATGAGCT- AAATCTCATAGG CTAAGCATGAACCTCACCTCCAAGACTCGGGGTTCCTAAATGGATGAGACCCTCTTT GGGAAGTCTTGTGGGCAGTGTCTAATTCCACTAGAAAAGTTTTACCTACAATTTAAACTTAAACCATGATATTT- TCTTACTGCTGT TTCCTTTTTTCATTTTCAGGTGGTATTACACAGACACGTGAGTTTATTGGTCTTTTATTTATGCCCTGTCTGAG- GATGCAGATTGGT GGGTAGATGAGAAGGAACTGATTGAGAGAGATTAACCCCAAGAACTGATATCTTCCCAGCATTGCATTCTCAAC- TCCATTTTAGA AAGGTTCCAAATAGGGACTTCTGTGGGTTTTTCTTTACATCCATCTTACCCTTCCCAAGTCCCCATGTCCCTGC- GTAAACCCTAAA GCCACCTCTCAAAAGGTTCTCTAGTTCCCTTCAAGGTTCTCTAGTTCCCTTCATTCCACATATCTCCTCTTCCA- CACCCTCTAGCCA GTAGAGCTCCCTTCTGACAAGCAAGTCTAAGATCTAGATGACAGATGACTTCCTGCATTTGGGTGGTTCTTTTG- TCACTAATTTGC CTTTTCTAAAATTGTCCTGGTTTCTTCTGCCAATTTCCCTTCTTTCTCCCCAGCATATAAAGTCTCCATCTCTG- GAACCACA -CAR7 of donor construct for inserting GFP into CD3 locus SEQ ID NO: 3057 atggccttaccagtgaccgccttgctcctgccgctggccttgctgctccacgccgccaggccggatatccagat- gacacagactacatcctccctgtctgcctctctgggagacagagtcaccatcagttgcagtgca agtcagggcattagcaattatttaaactggtatcagcagaaaccagatggaactgttaaactcctgatctatta- cacatcaagtttacactcaggagtcccatcaaggttcagtggcagtgggtctgggacagattattct ctcaccatcagcaacctggaacctgaagatattgccacttattattgtcagcagtatagcaagcttccgtacac- gttcggaggggggaccaagctggaaataaaacgtggtggtggtggttctggtggtggtggttctg gcggcggcggctccggtggtggtggatccgaggtgcaactggtggagtctgggggaggcttagtgaagcctggg- gggtccctgaaactctcctgtgcagcctctggactcactttcagtagctatgccatgtcttg ggttcgccagactccagagaagaggctggagtgggtcgcatccattagtagtggtggtttcacctactatccag- acagtgtgaagggccgattcaccatctccagagataatgccaggaacatcctgtatctgcaaat gagcagtctgaggtctgaggacacggccatgtattactgtgcaagagacgaggtacgggggtacctcgatgtct- ggggcgcagggaccacggtcaccgtttcccctaggGCTAGCaccacgacgccagcg ccgcgaccaccaacaccggcgcccaccatcgcgtcgcagcccctgtccctgcgcccagaggcgtgccggccagc- ggcggggggcgcagtgcacacgagggggctggacttcgcctgtgatttttgggtgctg gtggtggttggtggagtcctggcttgctatagcttgctagtaacagtggcctttattattttctgggtgaggag- taagaggagcaggctcctgcacagtgactacatgaacatgactccccgccgccccgggcccacc cgcaagcattaccagccctatgccccaccacgcgacttcgcagcctatcgctccagagtgaagttcagcaggag- cgcagacgcccccgcgtacaagcagggccagaaccagctctataacgagctcaatctagg acgaagagaggagtacgatgttttggacaagagacgtggccgggaccctgagatggggggaaagccgagaagga- agaaccctcaggaaggcctgtacaatgaactgcagaaagataagatggcggaggcct acagtgagattgggatgaaaggcgagcgccggaggggcaaggggcacgatggcctttaccagggtctcagtaca- gccaccaaggacacctacgacgcccttcacatgcaggccctgccccctcgcCGGA CCGATggaagcggagctactaacttcagcctgctgaagcaggctggagacgtggaggagaaccctggacctgtt- tctgaagccatgccgcggggctggaccgcgctttgcttgctgagtttgctgccttctgg gttcatgagtatgacaacaacggtactgctaccccagagttacctacccagggaacattttcaaatgtttctac- aaatgtatcctaccaagaaactacaacacctagtacccttggaagtaccagcctgcaccctgtgtc tcaacatggcaatgaggccacaacaaacatcacagaaacgacagtcaaattcacatctacctctgtgataacct- cagtttatggaaacacaaactcttctgtccagtcacagacctctgtaatcagcacagtgttcacca ccccagccaacgtttcaactccagagacaaccttgaagcctagcctgtcacctggaaatgtttcagacctttca- accactagcactagccttgcaacatctcccactaaaccctatacatcatcttctcctatcctaagt gacatcaaggcagaaatcaaatgttcaggcatcagagaagtgaaattgactcagggcatctgcctggagcaaaa- taagacctccagctgtgcggagtttaagaaggacaggggagagggcctggcccgagtgctg tgtggggaggagcaggctgatgctgatgctggggcccaggtatgctccctgctccttgcccagtctgaggtgag- gcctcagtgtctactgctggtcttggccaacagaacagaaatttccagcaaactccaacttatg aaaaagcaccaatctgacctgaaaaagctggggatcctagatttcactgagcaagatgttgcaagccaccagag- ctattcccaaaagaccctgattgcactggtcacctcgggagccctgctggctgtcttgggcat cactggctatttcctgatgaatcgccgcagctggagccccatttaa -GFP of donor construct for inserting into CD3 locus SEQ ID NO: 3058 ATGGTGAGCAAGGGCGAGGAGCTGTTCACCGGGGTGGTGCCCATCCTGGTCGAGCTGGACGGCGACGTAAACGG- CCACAAGTTC AGCGTGTCCGGCGAGGGCGAGGGCGATGCCACCTACGGCAAGCTGACCCTGAAGTTCATCTGCACCACCGGCAA- GCTGCCCGTG CCCTGGCCCACCCTCGTGACCACCCTGACCTACGGCGTGCAGTGCTTCAGCCGCTACCCCGACCACATGAAGCA- GCACGACTTCT TCAAGTCCGCCATGCCCGAAGGCTACGTCCAGGAGCGCACCATCTTCTTCAAGGACGACGGCAACTACAAGACC- CGCGCCGAGG TGAAGTTCGAGGGCGACACCCTGGTGAACCGCATCGAGCTGAAGGGCATCGACTTCAAGGAGGACGGCAACATC- CTGGGGCACA AGCTGGAGTACAACTACAACAGCCACAACGTCTATATCATGGCCGACAAGCAGAAGAACGGCATCAAGGTGAAC- TTCAAGATCC GCCACAACATCGAGGACGGCAGCGTGCAGCTCGCCGACCACTACCAGCAGAACACCCCCATCGGCGACGGCCCC- GTGCTGCTGC CCGACAACCACTACCTGAGCACCCAGTCCGCCCTGAGCAAAGACCCCAACGAGAAGCGCGATCACATGGTCCTG- CTGGAGTTCG TGACCGCCGCCGGGATCACTCTCGGCATGGACGAGCTGTACAAGTAA -hGMB poly A of donor construct for inserting GFP into CD3 locus SEQ ID NO: 3059 ACGGGTGGCATCCCTGTGACCCCTCCCCAGTGCCTCTCCTGGCCCTGGAAGTTGCCACTCCAGTGCCCACCAGC- CTTGTCCTAATA AAATTAAGTTGCATCATTTTGTCTGACTAGGTGTCCTTCTATAATATTATGGGGTGGAGGGGGGTGGTATGGAG- CAAGGGGCAAG TTGGGAAGACAACCTGTAGGGCCTGCGGGGTCTATTGGGAACCAAGCTGGAGTGCAGTGGCACAATCTTGGCTC- ACTGCAATCT CCGCCTCCTGGGTTCAAGCGATTCTCCTGCCTCAGCCTCCCGAGTTGTTGGGATTCCAGGCATGCATGACCAGG- CTCAGCTAATTT TTGTTTTTTTGGTAGAGACGGGGTTTCACCATATTGGCCAGGCTGGTCTCCAACTCCTAATCTCAGGTGATCTA- CCCACCTTGGCC TCCCAAATTGCTGGGATTACAGGCGTGAACCACTGCTCCCTTCCCTGTCCTTCTGATTTTGTAGGTAACCAC -CD3e R homology ARM of donor construct for inserting GFP into CD3 locus SEQ ID NO: 3060 aGTAtaatattgacatgccctcagtatcctggatctgaaatactatggcaacacaatgataaaaacataggcgg- tgatgaggatgataaaaacataggcagtgatgaggatcacctgtcactgaaggaattttcaga attggagcaaagtggttattatgtctgctaccccagaggaagcaaaccagaagatgcgaacttttatctctacc- tgagggcaagagtgtgtgagaactgcatggagatggatgtgatgtcggtggccacaattgtcata gtggacatctgcatcactgggggcttgctgctgctggtttactactggagcaagaatagaaaggccaaggccaa- gcctgtgacacgaggagcgggtgctggcggcaggcaaaggggacaaaacaaggagagg ccaccacctgttcccaacccagactatgagcccatccggaaaggccagcgggacctgtattctggcctgaatca- gagacgcatctgaccctctggagaacactgcctcccgctggcccaggtctcctctccagtcc ccctgcgactccctgtttcctgggctagtcttggaccccacgagagagaatcgttcctcagcctcatggtgaac- tcgcgccctccagcctgatcccccgctccctcctccctgccttctctgctggtacccagtcctaaa atattgctgcttcctcttcctttgaagcatcatcagtagtcacaccctcacagctggcctgccctcttgccagg- atatttatttgtgctattcactcccttccctttggatgtaacttctccgttcagttccctcctttt cttgcatgtaagttgtcccccatcccaaagtattccatctacttttctatcgccgtccccttttgcagccctct- ctggggatggactgggtaaatgttgacagaggccctgccccgttcacagatcctggccctgagcca gccctgtgctcctccctcccccaacactccctaccaacc -cloning remnants of donor construct for inserting GFP into CD3 locus SEQ ID NO: 3061 GCGgacCGAGCGGCCGC -right ITR of donor construct for inserting GFP into CD3 locus SEQ ID NO: 3062 AGGAACCCCTAGTGATGGAGTTGGCCACTCCCTCTCTGCGCGCTCGCTCGCTCACTGAGGCCGGGCGACCAAAG- GTCGCCCGACG CCCGGGCTTTGCCCGGGCGGCCTCAGTGAGCGAGCGAGCGCGCAGCTGCCTGCAGG -cloning remnants of donor construct for inserting GFP into CDR locus SEQ ID NO: 3063 CCTGCAGGCAGCTGCGCGCTCGCTCGCTCACTGAGGCCGCCCGGGCGTCGGGCGACCTTTGGTCGCCCGGCCTC- AGTGAGCGAGC GAGCGCGCAGAGAGGGAGTGGCCAACTCCATCACTAGGGGTTCCTGCGGCCGCATCGATTGaattcAGGTAAGT- CCACGAATCAGT GATTCAGTGGTGTGGAGAGCTTTATTTCTGAGAAGGCCAGTAGCGCTCCCTTCTGACAAGCAAATCTAAGACCT- GGATGACAGAT GACTTCCTGCATTTGGTTGGTTCTTTTGTCATTCATATCTATCTGTAATACAGTTCTGGCTAATTTAAGAGGAT- AAGCTTGAAGAC CTCTGGAATTTTTCGGCTTTAGGACTTTAAGGCTTTCTGAGCTTCAGTAGATCTAGAT CTAGGAGCTCATGCTGGTATATTCTGAATCCGATGTATCTGAGTTACATCTATGAGCTACTTAATAAATATATC- TATGAGCTAAAT CTCATAGGCTAAGCATGAACCTCACCTCCAAGACTCGGGGTTCCTAAATGGATGAGACCCTCTTTGGGAAGTCT- TGTGGGCAGTG TCTAATTCCACTAGAAAAGTTTTACCTACAATTTAAACTTAAACCATGATATTTTCTTACTGCTGTTTCCTTTT- TTCATTTTCAGGT GGTATTACACAGACACGTGAGTTTATTGGTCTTTTATTTATGCCCTGTCTGAGGATGCAGATTGGTGGGTAGAT- GAGAAGGAACT GATTGAGAGAGATTAACCCCAAGAACTGATATCTTCCCAGCATTGCATTCTCAACTC CATTTTAGAAAGGTTCCAAATAGGGACTTCTGTGGGTTTTTCTTTACATCCATCTTACCCTTCCCAAGTCCCCA- TGTCCCTGCGTA AACCCTAAAGCCACCTCTCAAAAGGTTCTCTAGTTCCCTTCAAGGTTCTCTAGTTCCCTTCATTCCACATATCT- CCTCTTCCACACC CTCTAGCCAGTAGAGCTCCCTTCTGACAAGCAAGTCTAAGATCTAGATGACAGATGACTTCCTGCATTTGGGTG- GTTCTTTTGTCA CTAATTTGCCTTTTCTAAAATTGTCCTGGTTTCTTCTGCCAATTTCCCTTCTTTCTCCCCAGCATATAAAGTCT- CCATCTCTGGAAC CACAATGGTGAGCAAGGGCGAGGAGCTGTTCACCGGGGTGGTGCCCATCCTGGTCGAGCTGGACGGCGACGTAA- ACGGCCACAA GTTCAGCGTGTCCGGCGAGGGCGAGGGCGATGCCACCTACGGCAAGCTGACCCTGAAGTTCATCTGCACCACCG- GCAAGCTGCC CGTGCCCTGGCCCACCCTCGTGACCACCCTGACCTACGGCGTGCAGTGCTTCAGCCGCTACCCCGACCACATGA- AGCAGCACGAC TTCTTCAAGTCCGCCATGCCCGAAGGCTACGTCCAGGAGCGCACCATCTTCTTCAAGGACGACGGCAACTACAA- GACCCGCGCCG AGGTGAAGTTCGAGGGCGACACCCTGGTGAACCGCATCGAGCTGAAGGGCATCGACTTCAAGGAGGACGGCAAC- ATCCTGGGG CACAAGCTGGAGTACAACTACAACAGCCACAACGTCTATATCATGGCCGACAAGCAGAAGAACGGCATCAAGGT- GAACTTCAAG ATCCGCCACAACATCGAGGACGGCAGCGTGCAGCTCGCCGACCACTACCAGCAGAACACCCCCATCGGCGACGG- CCCCGTGCTG CTGCCCGACAACCACTACCTGAGCACCCAGTCCGCCCTGAGCAAAGACCCCAACGAGAAGCGCGATCACATGGT- CCTGCTGGAG TTCGTGACCGCCGCCGGGATCACTCTCGGCATGGACGAGCTGTACAAGTAAACGGGTGGCATCCCTGTGACCCC- TCCCCAGTGCC TCTCCTGGCCCTGGAAGTTGCCACTCCAGTGCCCACCAGCCTTGTCCTAATAAAATTAAGTTGCATCATTTTGT- CTGACTAGGTGT CCTTCTATAATATTATGGGGTGGAGGGGGGTGGTATGGAGCAAGGGGCAAGTTGGGAAGACAACCTGTAGGGCC- TGCGGGGTCT ATTGGGAACCAAGCTGGAGTGCAGTGGCACAATCTTGGCTCACTGCAATCTCCGCCTCCTGGGTTCAAGCGATT- CTCCTGCCTCA GCCTCCCGAGTTGTTGGGATTCCAGGCATGCATGACCAGGCTCAGCTAATTTTTGTTTTTTTGGTAGAGACGGG-

GTTTCACCATAT TGGCCAGGCTGGTCTCCAACTCCTAATCTCAGGTGATCTACCCACCTTGGCCTCCCAAATTGCTGGGATTACAG- GCGTGAACCAC TGCTCCCTTCCCTGTCCTTCTGATTTTGTAGGTAACCACaGTAtaatattgacatgccctcagtatcctggatc- tgaaatactatggcaacacaatgataaaaacataggcggtg atgaggatgataaaaacataggcagtgatgaggatcacctgtcactgaaggaattttcagaattggagcaaagt- ggttattatgtctgctaccccagaggaagcaaaccagaagatgcgaacttttatctctacctgag ggcaagagtgtgtgagaactgcatggagatggatgtgatgtcggtggccacaattgtcatagtggacatctgca- tcactgggggcttgctgctgctggtttactactggagcaagaatagaaaggccaaggccaag cctgtgacacgaggagcgggtgctggcggcaggcaaaggggacaaaacaaggagaggccaccacctgttcccaa- cccagactatgagcccatccggaaaggccagcgggacctgtattctggcctgaatcag agacgcatctgaccctctggagaacactgcctcccgctggcccaggtctcctctccagtccccctgcgactccc- tgtttcctgggctagtcttggaccccacgagagagaatcgttcctcagcctcatggtgaactcg cgccctccagcctgatcccccgctccctcctccctgccttctctgctggtacccagtcctaaaatattgctgct- tcctcttcctttgaagcatcatcagtagtcacaccctcacagctggcctgccctcttgccaggata tttatttgtgctattcactcccttccattggatgtaacttctccgttcagttccctccttttcttgcatgtaag- ttgtcccccatcccaaagtattccatctacttttctatcgccgtccccttttgcagccctctctgg ggatggactgggtaaatgttgacagaggccctgccccgttcacagatcctggccctgagccagccctgtgctcc- tccctcccccaacactccctaccaaccGCGgacCGAGCGGCCGCAGGAACCCCTAG TGATGGAGTTGGCCACTCCCTCTCTGCGCGCTCGCTCGCTCACTGAGGCCGGGCGACCAAAGGTCGCCCGACGC- CCGGGCTTTGC CCGGGCGGCCTCAGTGAGCGAGCGAGCGCGCAGCTGCCTGCAGG -complete sequence of vector for insertion of GFP into CD3e locus SEQ ID NO: 3064 CCTGCAGGCAGCTGCGCGCTCGCTCGCTCACTGAGGCCGCCCGGGCGTCGGGCGACCTTTGGTCGCCCGGCCTC- AGTGAGCGAGC GAGCGCGCAGAGAGGGAGTGGCCAACTCCATCACTAGGGGTTCCTGCGGCCGCATCGATTGaattcAGGTAAGT- CCACGAATCAGT GATTCAGTGGTGTGGAGAGCTTTATTTCTGAGAAGGCCAGTAGCGCTCCCTTCTGACAAGCAAATCTAAGACCT- GGATGACAGAT GACTTCCTGCATTTGGTTGGTTCTTTTGTCATTCATATCTATCTGTAATACAGTTCTGGCTAATTTAAGAGGAT- AAGCTTGAAGAC CTCTGGAATTTTTCGGCTTTAGGACTTTAAGGCTTTCTGAGCTTCAGTAGATCTAGAT CTAGGAGCTCATGCTGGTATATTCTGAATCCGATGTATCTGAGTTACATCTATGAGCTACTTAATAAATATATC- TATGAGCTAAAT CTCATAGGCTAAGCATGAACCTCACCTCCAAGACTCGGGGTTCCTAAATGGATGAGACCCTCTTTGGGAAGTCT- TGTGGGCAGTG TCTAATTCCACTAGAAAAGTTTTACCTACAATTTAAACTTAAACCATGATATTTTCTTACTGCTGTTTCCTTTT- TTCATTTTCAGGT GGTATTACACAGACACGTGAGTTTATTGGTCTTTTATTTATGCCCTGTCTGAGGATGCAGATTGGTGGGTAGAT- GAGAAGGAACT GATTGAGAGAGATTAACCCCAAGAACTGATATCTTCCCAGCATTGCATTCTCAACTC CATTTTAGAAAGGTTCCAAATAGGGACTTCTGTGGGTTTTTCTTTACATCCATCTTACCCTTCCCAAGTCCCCA- TGTCCCTGCGTA AACCCTAAAGCCACCTCTCAAAAGGTTCTCTAGTTCCCTTCAAGGTTCTCTAGTTCCCTTCATTCCACATATCT- CCTCTTCCACACC CTCTAGCCAGTAGAGCTCCCTTCTGACAAGCAAGTCTAAGATCTAGATGACAGATGACTTCCTGCATTTGGGTG- GTTCTTTTGTCA CTAATTTGCCTTTTCTAAAATTGTCCTGGTTTCTTCTGCCAATTTCCCTTCTTTCTCCCCAGCATATAAAGTCT- CCATCTCTGGAAC CACAatggccttaccagtgaccgccttgctcctgccgctggccttgctgctccacgccgccaggccggatatcc- agatgacacagactacatcctccctgtctgcctctctgggagacagagtcaccatcagttg cagtgcaagtcagggcattagcaattatttaaactggtatcagcagaaaccagatggaactgttaaactcctga- tctattacacatcaagtttacactcaggagtcccatcaaggttcagtggcagtgggtctgggaca gattattctctcaccatcagcaacctggaacctgaagatattgccacttattattgtcagcagtatagcaagct- tccgtacacgttcggaggggggaccaagctggaaataaaacgtggtggtggtggttctggtggtg gtggttctggcggcggcggctccggtggtggtggatccgaggtgcaactggtggagtctgggggaggcttagtg- aagcctggggggtccctgaaactctcctgtgcagcctctggactcactttcagtagctatgc catgtcttgggttcgccagactccagagaagaggctggagtgggtcgcatccattagtagtggtggtttcacct- actatccagacagtgtgaagggccgattcaccatctccagagataatgccaggaacatcctgta tctgcaaatgagcagtctgaggtctgaggacacggccatgtattactgtgcaagagacgaggtacgggggtacc- tcgatgtctggggcgcagggaccacggtcaccgtttcccctaggGCTAGCaccacga cgccagcgccgcgaccaccaacaccggcgcccaccatcgcgtcgcagcccctgtccctgcgcccagaggcgtgc- cggccagcggcggggggcgcagtgcacacgagggggctggacttcgcctgtgatttt tgggtgctggtggtggttggtggagtcctggcttgctatagcttgctagtaacagtggcctttattattttctg- ggtgaggagtaagaggagcaggctcctgcacagtgactacatgaacatgactccccgccgccccg ggcccacccgcaagcattaccagccctatgccccaccacgcgacttcgcagcctatcgctccagagtgaagttc- agcaggagcgcagacgcccccgcgtacaagcagggccagaaccagctctataacgagct caatctaggacgaagagaggagtacgatgttttggacaagagacgtggccgggaccctgagatggggggaaagc- cgagaaggaagaaccctcaggaaggcctgtacaatgaactgcagaaagataagatgg cggaggcctacagtgagattgggatgaaaggcgagcgccggaggggcaaggggcacgatggcctttaccagggt- ctcagtacagccaccaaggacacctacgacgcccttcacatgcaggccctgccccctc gcCGGACCGATggaagcggagctactaacttcagcctgctgaagcaggctggagacgtggaggagaaccctgga- cctgtttctgaagccatgccgcggggctggaccgcgctttgcttgctgagtttgct gccttctgggttcatgagtcttgacaacaacggtactgctaccccagagttacctacccagggaacattttcaa- atgtttctacaaatgtatcctaccaagaaactacaacacctagtacccttggaagtaccagcctgc accctgtgtctcaacatggcaatgaggccacaacaaacatcacagaaacgacagtcaaattcacatctacctct- gtgataacctcagtttatggaaacacaaactcttctgtccagtcacagacctctgtaatcagcaca gtgttcaccaccccagccaacgtttcaactccagagacaaccttgaagcctagcctgtcacctggaaatgtttc- agacctttcaaccactagcactagccttgcaacatctcccactaaaccctatacatcatcttctcc tatcctaagtgacatcaaggcagaaatcaaatgttcaggcatcagagaagtgaaattgactcagggcatctgcc- tggagcaaaataagacctccagctgtgcggagtttaagaaggacaggggagagggcctggc ccgagtgctgtgtggggaggagcaggctgatgctgatgctggggcccaggtatgctccctgctccttgcccagt- ctgaggtgaggcctcagtgtctactgctggtcttggccaacagaacagaaatttccagcaaac tccaacttatgaaaaagcaccaatctgacctgaaaaagctggggatcctagatttcactgagcaagatgttgca- agccaccagagctattcccaaaagaccctgattgcactggtcacctcgggagccctgctggct gtcttgggcat cactggctatttcctgatgaatcgccgcagctggagccccatttaaACGGGTGGCATCCCTGTGACCCCTCCCC- AGTGCCTCTCCTGGCCCTGGAAGTTGCCA CTCCAGTGCCCACCAGCCTTGTCCTAATAAAATTAAGTTGCATCATTTTGTCTGACTAGGTGTCCTTCTATAAT- ATTATGGGGTGG AGGGGGGTGGTATGGAGCAAGGGGCAAGTTGGGAAGACAACCTGTAGGGCCTGCGGGGTCTATTGGGAACCAAG- CTGGAGTGC AGTGGCACAATCTTGGCTCACTGCAATCTCCGCCTCCTGGGTTCAAGCGATTCTCCTGCCTCAGCCTCCCGAGT- TGTTGGGATTCC AGGCATGCATGACCAGGCTCAGCTAATTTTTGTTTTTTTGGTAGAGACGGGGTTTCACCATATTGGCCAGGCTG- GTCTCCAACTCC TAATCTCAGGTGATCTACCCACCTTGGCCTCCCAAATTGCTGGGATTACAGGCGTGAACCACTGCTCCCTTCCC- TGTCCTTCTGAT TTTGTAGGTAACCACaGTAtaatattgacatgccctcagtatcctggatctgaaatactatggcaacacaatga- taaaaacataggcggtgatgaggatgataaaaacataggcagtgatgaggatc acctgtcactgaaggaattttcagaattggagcaaagtggttattatgtctgctaccccagaggaagcaaacca- gaagatgcgaacttttatctctacctgagggcaagagtgtgtgagaactgcatggagatggatgt gatgtcggtggccacaattgtcatagtggacatctgcatcactgggggcttgctgctgctggtttactactgga- gcaagaatagaaaggccaaggccaagcctgtgacacgaggagcgggtgctggcggcaggca aaggggacaaaacaaggagaggccaccacctgttcccaacccagactatgagcccatccggaaaggccagcggg- acctgtattctggcctgaatcagagacgcatctgaccctctggagaacactgcctcccg ctggcccaggtctcctctccagtccccctgcgactccctgtttcctgggctagtcttggaccccacgagagaga- atcgttcctcagcctcatggtgaactcgcgccctccagcctgatcccccgctccctcctccctgc cttctctgctggtacccagtcctaaaatattgctgcttcctcttcctttgaagcatcatcagtagtcacaccct- cacagctggcctgccctcttgccaggatatttatttgtgctattcactcccttccctttggatgta acttctccgttcagttccctccttttcttgcatgtaagttgtcccccatcccaaagtattccatctacttttct- atcgccgtccccttttgcagccctctctggggatggactgggtaaatgttgacagaggccctgccc cgttcacagatcctggccctgagccagccctgtgctcctccctcccccaacactccctaccaaccGCGgacCGA- GCGGCCGCAGGAACCCCTAGTGATGGAGTTGGCCACTCCCTCT CTGCGCGCTCGCTCGCTCACTGAGGCCGGGCGACCAAAGGTCGCCCGACGCCCGGGCTTTGCCCGGGCGGCCTC- AGTGAGCGAG CGAGCGCGCAGCTGCCTGCAGG

[0458] All references, patents or applications, U.S. or foreign, cited in the application are hereby incorporated by reference as if written herein in their entireties. Where any inconsistencies arise, material literally disclosed herein controls.

[0459] From the foregoing description, one skilled in the art can easily ascertain the essential characteristics of this invention, and without departing from the spirit and scope thereof, can make various changes and modifications of the invention to adapt it to various usages and conditions.

TABLE-US-00027 E 0.172 0.17 0.073 0.075 0.085 0.084 0.492 0.557 0.42 0.18 0.247 0.19 450 [Test] 0.046 0.045 0.044 0.046 0.045 0.045 0.05 0.053 0.05 0.048 0.048 0.047 540 [Ref] 0.698 0.691 0.161 0.161 0.222 0.216 2.46 2.796 2.054 0.735 1.107 0.794 Pathlength 0.171 0.17 0.073 0.075 0.085 0.084 0.496 0.558 0.42 0.181 0.249 0.19 450 0.046 0.046 0.045 0.047 0.045 0.045 0.05 0.053 0.051 0.048 0.049 0.047 540 0.245 0.246 0.454 0.468 0.383 0.389 0.202 0.2 0.204 0.246 0.225 0.239 Corrected [450] 0.066 0.066 0.277 0.291 0.204 0.209 0.02 0.019 0.025 0.066 0.044 0.059 Corrected [540] F 0.127 0.124 0.07 0.074 0.075 0.072 0.148 0.143 0.128 0.102 0.115 0.121 450 [Test] 0.044 0.045 0.043 0.047 0.046 0.044 0.055 0.057 0.045 0.045 0.051 0.048 540 [Ref] 0.458 0.436 0.147 0.15 0.162 0.157 0.516 0.479 0.463 0.316 0.353 0.406 Pathlength 0.127 0.124 0.07 0.074 0.075 0.072 0.147 0.144 0.129 0.102 0.116 0.12 450 0.045 0.045 0.044 0.047 0.046 0.044 0.055 0.057 0.045 0.045 0.052 0.048 540 0.277 0.283 0.475 0.493 0.465 0.462 0.286 0.3 0.278 0.323 0.328 0.296 Corrected [450] 0.097 0.104 0.297 0.314 0.285 0.283 0.106 0.119 0.097 0.144 0.147 0.119 Corrected [540] G 0.098 0.1 0.078 0.073 0.104 0.122 0.143 0.169 0.144 0.125 0.134 0.131 450 [Test] 0.044 0.044 0.046 0.044 0.045 0.05 0.049 0.049 0.05 0.05 0.045 0.046 540 [Ref] 0.301 0.313 0.179 0.161 0.326 0.398 0.523 0.667 0.523 0.415 0.493 0.469 Pathlength 0.099 0.101 0.078 0.073 0.103 0.122 0.144 0.169 0.144 0.125 0.133 0.13 450 0.044 0.044 0.046 0.044 0.045 0.05 0.05 0.049 0.05 0.05 0.045 0.045 540 0.328 0.322 0.437 0.452 0.317 0.306 0.275 0.254 0.275 0.301 0.269 0.277 Corrected [450] 0.148 0.142 0.259 0.272 0.138 0.127 0.095 0.074 0.096 0.12 0.091 0.096 Corrected [540] H 0.082 0.087 0.113 0.12 0.074 0.081 0.165 0.169 0.15 0.103 0.122 0.119 450 [Test] 0.047 0.051 0.049 0.047 0.047 0.053 0.055 0.059 0.045 0.044 0.046 0.044 540 [Ref] 0.197 0.197 0.356 0.406 0.15 0.157 0.611 0.607 0.579 0.329 0.422 0.412 Pathlength 0.082 0.087 0.113 0.12 0.074 0.081 0.165 0.169 0.15 0.103 0.122 0.118 450 0.047 0.052 0.049 0.047 0.047 0.053 0.055 0.06 0.046 0.044 0.046 0.045 540 0.415 0.443 0.316 0.296 0.493 0.516 0.27 0.279 0.259 0.314 0.289 0.288 Corrected [450] 0.236 0.263 0.137 0.117 0.311 0.338 0.09 0.098 0.079 0.134 0.11 0.109 Corrected [540]

Sequence CWU 0 SQTB SEQUENCE LISTING The patent application contains a lengthy "Sequence Listing" section. A copy of the "Sequence Listing" is available in electronic form from the USPTO web site (http://seqdata.uspto.gov/?pageRequest=docDetail&DocID=US20200054675A1). An electronic copy of the "Sequence Listing" will also be available from the USPTO upon request and payment of the fee set forth in 37 CFR 1.19(b)(3).

0 SQTB SEQUENCE LISTING The patent application contains a lengthy "Sequence Listing" section. A copy of the "Sequence Listing" is available in electronic form from the USPTO web site (http://seqdata.uspto.gov/?pageRequest=docDetail&DocID=US20200054675A1). An electronic copy of the "Sequence Listing" will also be available from the USPTO upon request and payment of the fee set forth in 37 CFR 1.19(b)(3).

Claims

1. A chimeric antigen receptor (CAR)-bearing immune effector cell that is deficient in a cytokine or in a chemokine or in a transcription factor that is involved in cytokine release syndrome.

2. The cell as recited in claim 1, wherein the cytokine or chemokine or transcription factor deficiency is effected by deletion or suppression of a gene encoding the cytokine or chemokine or transcription factor, or by suppression of a gene transcript of the cytokine or chemokine or transcription factor gene.

3. The cell as recited in claim 2, wherein the deletion or suppression of the gene encoding the cytokine or chemokine or transcription factor is effected by inserting the CAR into a locus of the cytokine or chemokine or transcription factor gene, or wherein the suppression of the gene transcript of the cytokine or chemokine or transcription factor is effected by transfection of one or more types of small interfering RNAs (siRNA) or by transduction of one or more types of short hairpin RNAs (shRNA).

4. The cell as recited in claim 3, wherein the CAR is part of a construct that also includes a selectable marker chosen from a green fluorescence (GFP) gene, a YFP gene, a tCD34 gene, or a tEGFR gene.

5.-6. (canceled)

7. The cell as recited in claim 1, wherein deletion or suppression is effected using CRISPR, Cas9-CRISPR, Transcription Activator-like Effector Nucleases (TALENs), Zinc Finger Nucleases (ZFNs), or Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR).

8. (canceled)

9. The cell as recited in claim 7, wherein the Cas9 is delivered into the cell as mRNA or protein, and/or wherein a guide RNA (gRNA) targeting the gene to be deleted or suppressed is delivered contemporaneously with the Cas9.

10.-15. (canceled)

16. The cell of claim 2, wherein: the cell expresses at least one CAR that is inserted into a locus of the gene encoding the cytokine or chemokine or transcription factor; the gene encoding the cytokine or chemokine or transcription factor is deleted or suppressed by a method chosen from Transcription Activator-like Effector Nucleases (TALENs), Zinc Finger Nucleases (ZFNs), and Clustered Regularly Interspaces Short Palindromic Repeats (CRISPR) editing; the cytokine or chemokine or transcription factor is suppressed by expression of an scFv with an endoplasmic reticulum (ER) binding tether to bind the cytokine or chemokine in the ER and prevent secretion; the cytokine or chemokine or transcription factor gene transcript is suppressed by transfection of small interfering RNAs (siRNAs); the cytokine or chemokine or transcription factor gene transcript is suppressed by transduction of short hairpin RNAs (shRNAs); or the gene that is deleted or suppressed is a T cell surface receptor that is integrated into CAR-T cell signaling.

17. The cell as recited in claim 1, wherein the cell is chosen from a chimeric antigen receptor T cell (CAR-T), a CAR-bearing iNKT cell (iNKT-CAR), and a CAR-bearing natural killer (NK) cell (NK-CAR), or a CAR-bearing macrophage.

18. (canceled)

19. The cell as recited in claim 17, wherein the cell is a dual or tandem CAR-T or iNKT-CAR or CAR-bearing macrophage.

20.-23. (canceled)

24. The cell as recited in claim 1, wherein the cytokine or chemokine or transcription factor contributes to the development of cytokine release syndrome and is selected from among those recited in Table 10.

25. (canceled)

26. The cell as recited in claim 24, wherein the cytokine or chemokine or transcription factor is produced by T cells that activate or localize myeloid cells, or is a T cell surface receptor gene that activates myeloid or CAR-T cells.

27.-28. (canceled)

29. The cell as recited in claim 1, wherein the cytokine or chemokine or transcription factor drives T cell/CAR-T cell differentiation, or wherein the cytokine or chemokine is a transcription factor that drives T cell/CAT-T cell differentiation.

30. (canceled)

31. The cell as recited in claim 1, wherein the cytokine or chemokine or transcription factor is chosen from MCP1 (CCL2), MCP-2, GM-CSF, G-CSF, M-CSF, Il-4, and IFN.gamma..

32. (canceled)

33. The cell as recited in claim 31, wherein the cell is a GM-CSF deficient CAR-T cell or a GM-CSF deficient iNKT-CAR cell.

34.-36. (canceled)

37. The cell as recited in claim 1, wherein the chimeric antigen receptor(s) specifically binds at least one antigen expressed on a malignant cell, a malignant T cell, a malignant B cell, a malignant mesothelial cell, or a malignant plasma cell.

38. The cell as recited in claim 37, wherein the at least one antigen expressed on a malignant cell is chosen from BCMA, CS1, CD38, CD138, CD19, CD33, CD123, CD371, CD117, CD135, Tim-3, CD5, CD7, CD2, CD4, CD3, CD79A, CD79B, APRIL, CD56, and CD1a; or wherein the at least one antigen expressed on a malignant T cell is chosen from CD2, CD3.epsilon., CD4, CD5, CD7, TCRA, and TCR.beta.; or wherein the at least one antigen expressed on a malignant B cell is chosen from CD19, CD20, CD21, CD22, CD23, CD24, CD25, CD27, CD38, and CD45; or wherein the at least one antigen expressed on a malignant mesothelial cell is mesothelin; or wherein the at least one antigen expressed on a malignant plasma cell is chosen from BCMA, CS1, CD38, and CD19.

39.-47. (canceled)

48. The cell as recited in claim 37, wherein the chimeric antigen receptor expresses the extracellular portion of the APRIL protein, the ligand for BCMA and TACI, effectively co-targeting both BCMA and TACI.

49. (canceled)

50. The cell as recited in claim 1, wherein endogenous T cell receptor mediated signaling is negligible in the cell.

51. The cell as recited in claim 50, wherein the cell does not induce alloreactivity, graft-versus-host disease, or fratricide.

52. (canceled)

53. A method of treatment of cancer in a patient, which has a reduced incidence of cytokine release syndrome and/or CAR-T associated neuropathy, comprising the administration of cells as recited in claim 1.

54. The method as recited in claim 53, wherein the cancer is a hematologic malignancy chosen from a T-cell malignancy, multiple myeloma, or acute myeloid leukemia (AML), or a solid tumor chosen from cervical cancer, pancreatic cancer, ovarian cancer, mesothelioma, or lung cancer.

55. (canceled)

56. The method as recited in claim 54, wherein the T cell malignancy is T-cell acute lymphoblastic leukemia (T-ALL), or non-Hodgkin's lymphoma.

57.-61. (canceled)

61. A method of prevention or reduction of cytokine release syndrome or CAR-T associated neuropathy in a patient being treated for cancer and receiving chimeric antigen receptor T cell (CAR-T), CAR-bearing iNKT cell (iNKT-CAR), CAR-bearing natural killer (NK) cell (NK-CAR), or CAR-bearing macrophage (CAR-macrophage) immunotherapy, comprising the administration of cells as recited in claim 1 as the immunotherapy.

62. (canceled)

63. The method as recited in claim 62, wherein the cancer is a hematologic malignancy chosen from T-cell malignancy, multiple myeloma, or AML, or a solid tumor chosen from cervical cancer, pancreatic cancer, ovarian cancer, mesothelioma, or lung cancer.

64. (canceled)

65. The method as recited in claim 64, wherein the T cell malignancy is T-cell acute lymphoblastic leukemia (T-ALL) or non-Hodgkin's lymphoma.

66.-73. (canceled)

74. A method of making a CAR-T (immune effector) cell that does not cause or contribute to CRS or CAR-T-associated neuropathy (CAN) comprising deleting or suppressing a cytokine or chemokine or transcription factor gene, wherein deleting or suppressing the cytokine or chemokine or transcription factor gene does not reduce CAR-T cell-mediated killing.

75. (canceled)

76. The method as recited in claim 74, wherein the deletion or suppression is effected by inserting the CAR into a locus of the cytokine or chemokine or transcription factor gene, by suppression of the cytokine or chemokine or transcription factor gene transcript by transduction of one or more types of short hairpin RNAs (shRNA), or by transducing a construct encoding a protein expression blocker (PEBL).

77. The method as recited in claim 74, wherein the CAR is part of a construct that also includes a selectable marker chosen from a green fluorescence (GFP) gene, a YFP gene, a tCD34 gene, or a tEGFR gene.

78. (canceled)

79. The method of claim 74, wherein the insertion of a CAR with a selectable marker into the cytokine or chemokine or transcription factor gene allows a single-step purification of TCR-negative cells or CAR+ cytokine negative cells.

80. (canceled)

81. The method as recited in claim 74, wherein the deletion or suppression is effected using Transcription Activator-like Effector Nucleases (TALENs), Zinc Finger Nucleases (ZFNs), Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR), or Cas9-CRISPR.

82.-83. (canceled)

84. The method as recited in claim 81, wherein the Cas9 is delivered into the cell as mRNA or protein and/or wherein a guide RNA (gRNA) targeting the gene to be deleted or suppressed is delivered contemporaneously with the Cas9.

85.-90. (canceled)

91. The method of claim 76, wherein the construct encodes an antibody-derived single-chain variable fragment specific for the cytokine, chemokine or transcription factor gene.

92.-94. (canceled)