PLAKOPHILIN-2 (PKP2) GENE THERAPY USING AAV VECTOR

Abstract

Provided herein is a gene therapy for PKP2 (Plakophilin-2), e.g. using an adeno-associated virus (AAV) vector. The promoter of the vector may be a MHCK7 promoter or a cardiac troponin T (HTNNT2) promoter. The capsid may be an AAV9 or AAVrh74 capsid or a functional variant thereof. Other promoters or capsids may be used. Further provided are methods of treatment, such as by intravenous, intracoronary, intracarotid or intracardiac administration of the rAAV vector, and other compositions and methods.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application is a continuation of International Application No. PCT/US2021/045220, filed Aug. 9, 2021, which claims the benefit of U.S. Provisional Application No. 63/063,032, filed Aug. 7, 2020, which is incorporated by reference herein in its entirety.

STATEMENT REGARDING THE SEQUENCE LISTING

[0002] The Sequence Listing associated with this application is provided in text format in lieu of a paper copy, and is hereby incorporated by reference into the specification. The name of the text file containing the Sequence Listing is ROPA_021_01WO_ST25.txt. The text file is about 212 KB, created on Aug. 8, 2021, and is being submitted electronically via EFS-Web.

BACKGROUND

[0003] Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a form of adult-onset heart disease, which impacts an estimated 1 in 1,000 to 1 in 1,250 people. It manifests as breakdown of the muscular wall of the heart (the myocardium) over time, which leads to increased risk of abnormal heartbeat (arrhythmia) and an increased risk of sudden death when an affected individual exercises strenuously. Individuals may also experience a sensation of fluttering or pounding in the chest (palpitations), light-headedness, fainting (syncope), shortness of breath, and abnormal swelling in the legs or abdomen. Over time, ARVC can lead to heart failure.

[0004] At least 13 genes are implicated in ARVC, many of which are involved in the biogenesis of desmosomes, which are intracellular junctions that provide strong adhesion between cells. When desmosomes fail to form properly, myocardial cells may detach from one another and die. The right ventricle in particular may develop weakness, while fatty deposits and scar tissue may replace the damaged myocardium, leading to distension of the right ventricle. These alterations ultimately prevent effective heart pumping and disrupt the electrical signals that control the heartbeat, leading to arrhythmia. Autosomal dominant plakophilin-2 (PKP2) cardiomyopathy is an inherited ARVC in which mutations affecting PKP2 are detected.

[0005] There remains, therefore, an unmet need in the art for treatments for PKP2-related diseases and disorders, including ARVC. The compositions and methods disclosed herein address this need.

SUMMARY

[0006] The present invention relates generally to gene therapy for a disease or disorder, e.g., a cardiac disease or disorder, using a vector expressing PKP2 or a functional variant thereof.

[0007] In one aspect, the disclosure provides polynucleotide, comprising an expression cassette and optionally flanking adeno-associated virus (AAV) inverted terminal repeats (ITRs), wherein the polynucleotide comprises a polynucleotide sequence encoding a Plakophilin-2 (PKP2) or a functional variant thereof, operatively linked to a promoter.

[0008] In some embodiments, the promoter is a cardiac-specific promoter.

[0009] In some embodiments, the promoter is a muscle-specific promoter.

[0010] In some embodiments, the promoter is a cardiomyocyte-specific promoter.

[0011] In some embodiments, the promoter is a Myosin Heavy-chain Creatine Kinase 7 (MHCK7) promoter.

[0012] In some embodiments, the MHCK7 promoter shares at least 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% identity with SEQ ID NO: 31.

[0013] In some embodiments, the promoter is a cardiac troponin T (hTNNT2) promoter.

[0014] In some embodiments, the hTNNT2 promoter shares at least 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% identity with SEQ ID NO: 32.

[0015] In some embodiments, the expression cassette comprises exon 1 of the cardiac troponin T (hTNNT2) gene, wherein optionally the hTNNT2 promoter and exon 1 together share at least 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% identity with SEQ ID NO: 32.

[0016] In some embodiments, the promoter is a ubiquitous promoter, optionally a CMV promoter or a CAG promoter.

[0017] In some embodiments, the expression cassette comprises a polyA signal.

[0018] In some embodiments, the polyA signal is a human growth hormone (hGH) polyA.

[0019] In some embodiments, the expression cassette comprises a Woodchuck Hepatitis Virus Posttranscriptional Regulatory Element (WPRE), optionally a WPRE(x).

[0020] In some embodiments, the Plakophilin-2 (PKP2) or functional variant thereof is a PKP2.

[0021] In some embodiments, the PKP2 is a functional PKP2.

[0022] In some embodiments, the PKP2 is a human PKP2.

[0023] In some embodiments, the PKP2 is PKP2 isoform A.

[0024] In some embodiments, the PKP2 isoform A shares at least 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% identity with SEQ ID NO: 1.

[0025] In some embodiments, the PKP2 is PKP2 isoform B.

[0026] In some embodiments, the PKP2 shares at least 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% identity with SEQ ID NO: 2.

[0027] In some embodiments, the polynucleotide sequence encoding PKP2 is a human PKP2 polynucleotide.

[0028] In some embodiments, the polynucleotide sequence encoding PKP2 shares at least 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% identity with SEQ ID NO: 3.

[0029] In some embodiments, the polynucleotide sequence encoding PKP2 shares at least 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% identity with SEQ ID NO: 4.

[0030] In some embodiments, the polynucleotide comprises at least about 4.0 kb, at least about 4.1 kb, at least about 4.2 kb, at least about 4.3 kb, at least about 4.4 kb, or at least about 4.5 kb.

[0031] In some embodiments, the polynucleotide comprises at most about 4.1 kb, at most about 4.2 kb, at most about 4.3 kb, at most about 4.4 kb, at most about 4.5 kb, or at most about 4.6 kb.

[0032] In some embodiments, the polynucleotide comprises 4.0 kb to 4.6 kb, 4.0 kb to 4.5 kb, or 4.0 kb to 4.4 kb or wherein the polynucleotide comprises 4.0 kb to 4.3 kb, 4.0 kb to 4.2 kb, or 4.0 kb to 4.1 kb.

[0033] In some embodiments, the PKP2 or functional variant thereof comprises at least 800 or at least 830 amino acids.

[0034] In some embodiments, the polynucleotide shares at least 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% identity with any one of SEQ ID NOs: 8-15.

[0035] In some embodiments, the expression cassette is flanked by 5' and 3' inverted terminal repeats (ITRs)

[0036] In some embodiments, the ITRs are AAV2 ITRs and/or the ITRs share at least 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% identity with any one of SEQ ID NO: 20-26.

[0037] In another aspect, the disclosure provides a gene therapy vector, comprising the polynucleotide of any one of the preceding embodiments.

[0038] In some embodiments, the gene therapy vector is a recombinant adeno-associated virus (rAAV) vector.

[0039] In some embodiments, the rAAV vector is an AAV9 or a functional variant thereof.

[0040] In some embodiments, the rAAV vector comprises a capsid protein that shares 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to any one of SEQ ID NO: 77.

[0041] In some embodiments, the rAAV vector is an AAVrh10 or a functional variant thereof.

[0042] In some embodiments, the rAAV vector comprises a capsid protein that shares 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to any one of SEQ ID NO: 79.

[0043] In some embodiments, the rAAV vector is an AAV6 or a functional variant thereof.

[0044] In some embodiments, the rAAV vector comprises a capsid protein that shares 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to any one of SEQ ID NO: 78.

[0045] In some embodiments, the rAAV vector is an AAVrh74 or a functional variant thereof.

[0046] In some embodiments, the rAAV vector comprises a capsid protein that shares 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100% identity to any one of SEQ ID NO: 80.

[0047] In another aspect, the disclosure provides a method of treating and/or preventing a disease or disorder in a subject in need thereof, comprising administering the vector of any one of the preceding embodiments to the subject.

[0048] In some embodiments, the disease or disorder is a cardiac disorder.

[0049] In some embodiments, the disease or disorder is cardiomyopathy.

[0050] In some embodiments, the cardiomyopathy is arrhythmogenic right ventricular cardiomyopathy (ARVC).

[0051] In some embodiments, the cardiomyopathy is hypertrophic cardiomyopathy or dilated cardiomyopathy.

[0052] In some embodiments, the disease or disorder is characterized by fibrofatty infiltration of myocardium.

[0053] In some embodiments, the disease or disorder is heart failure.

[0054] In some embodiments, the subject is a mammal.

[0055] In some embodiments, the subject is a primate.

[0056] In some embodiments, the subject is a human.

[0057] In some embodiments, the subject has a mutation in a PKP2 gene.

[0058] In some embodiments, the vector is administered by intravenous injection, intracardiac injection, intracardiac infusion, and/or cardiac catheterization.

[0059] In some embodiments, the administration increases PKP2 expression by at least about 5%.

[0060] In some embodiments, the administration increases PKP2 expression by at least about 30%.

[0061] In some embodiments, the administration increases PKP2 expression by at least about 70%.

[0062] In some embodiments, the administration increases PKP2 expression by about 5% to about 10%.

[0063] In some embodiments, the administration increases PKP2 expression by about 30% to about 50%.

[0064] In some embodiments, the administration increases PKP2 expression by about 50% to about 70%.

[0065] In some embodiments, the administration increases PKP2 expression by about 70% to about 100%.

[0066] In some embodiments, the method treats and/or prevents the disease or disorder.

[0067] In some embodiments, the method comprises administering an effective amount of the vector.

[0068] In some embodiments, the disease or disorder is related to or caused by loss of function in PKP2 in the subject.

[0069] In some embodiments, the disease or disorder is related to or caused by gain of function in PKP2 in the subject.

[0070] In some embodiments, the subject has a mutation that causes an amino acid substitution selected from p.Arg490Trp, Asp26Asn, Thr50 Va151SerfsX60, Arg79X, Tyr86X, Gln133X, Va1406SerfsX3, Tyr616X, Trp676X, Cys796Arg, Cys796E, Tyr807X, Glu62Lys, S688P, Trp848X, Y86X, V406X, Y616X, W848X, and Y807X, relative to a human PKP2 gene encoding a human PKP2 having the sequence of SEQ ID NO: 2.

[0071] In some embodiments, the method comprises administering a pharmaceutical composition comprising an effective amount of the vector.

[0072] In some embodiments, the method comprises administering between about 1.times.10.sup.11 vector genomes and about 1.times.10.sup.13 vector genomes of the vector to the subject, administering between about 1.times.10.sup.12 vector genomes and about 1.times.10.sup.14 vector genomes of the vector to the subject, or administering between about 1.times.10.sup.13 vector genomes and about 1.times.10.sup.15 vector genomes of the vector to the subject.

[0073] In another aspect, the disclosure provides a pharmaceutical composition comprising the vector of any one of the preceding embodiments.

[0074] In another aspect, the disclosure provides a kit comprising the vector of any one of the preceding embodiments or the pharmaceutical composition of the preceding embodiment and optionally instructions for use.

[0075] In another aspect, the disclosure provides a use of the vector of any one of the preceding embodiments in treating a disease or disorder, optionally according to the method of any one of the preceding embodiments.

[0076] In another aspect, the disclosure provides a vector according to any one of the preceding embodiments for use in treating a disease or disorder, optionally according to the method of any one of the preceding embodiments.

[0077] In another aspect, the disclosure provides a polynucleotide, comprising a polynucleotide sequences that shares at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to any one of SEQ ID NOs: 12-15 and 89-92 or to any one of SEQ ID NOs: 8-11 and 93-96.

[0078] In some embodiments, the promoter is a MHCK7 promoter.

[0079] In some embodiments, the MHCK7 promoter shares at least 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% identity with SEQ ID NO: 31.

[0080] In some embodiments, the PKP2 is a human PKP2.

[0081] In some embodiments, the PKP2 is PKP2 isoform A.

[0082] In some embodiments, the PKP2 isoform A shares at least 80%, 90%, 95%, 99% or 100% identity with SEQ ID NO: 1.

[0083] In another aspect, the disclosure provides a gene therapy vector, comprising the polynucleotide of any one of the preceding embodiments.

[0084] In some embodiments, the gene therapy vector is a recombinant adeno-associated virus (rAAV) vector.

[0085] In some embodiments, the rAAV vector is an AAV9 vector.

[0086] In some embodiments, the rAAV vector is an AAVrh74 vector.

[0087] In another aspect, the disclosure provides a method of treating and/or preventing a cardiac disorder in a subject identified as having a mutation in the PRP2 gene, comprising administering the vector of any one of the preceding embodiments to the subject.

[0088] In some embodiments, the cardiac disorder is cardiomyopathy, optionally arrhythmogenic right ventricular cardiomyopathy (ARVC), hypertrophic cardiomyopathy, or dilated cardiomyopathy.

[0089] In some embodiments, the cardiac disorder is heart failure.

[0090] In some embodiments, the subject is a mammal.

[0091] In some embodiments, the vector is administered by intravenous injection, intracardiac injection, intracardiac infusion, and/or cardiac catheterization.

[0092] In some embodiments, the method prevents or reduces a decrease in left ventricle ejection fraction percentage (LVEF %), optionally by about 50%, about 60%, about 70%, about 80%, about 90%, or about 100% compared to the decrease observed in an untreated subject identified as having a mutation in the PRP2 gene.

[0093] In some embodiments, the method prevents or reduces a decrease in left ventricle fractional shortening percentage (FS %), optionally by about 50%, about 60%, about 70%, about 80%, about 90%, or about 100% compared to the decrease observed in an untreated subject identified as having a mutation in the PRP2 gene.

[0094] In some embodiments, the method prevents or reduces an increase in right ventricle area in millimeters squared (RV Area (mm2), optionally by about 50%, about 60%, about 70%, about 80%, about 90%, or about 100% compared to the increase observed in an untreated subject identified as having a mutation in the PRP2 gene.

[0095] In some embodiments, the method prevents or reduces a decrease in right ventricle velocity time integral in millimeters per second (RV VTI (mm/sec), optionally by about 50%, about 60%, about 70%, about 80%, about 90%, or about 100% compared to the decrease observed in an untreated subject identified as having a mutation in the PRP2 gene.

[0096] In some embodiments, the method prevents or reduces an increase in left ventricle or right ventricle fibrosis, optionally by about 50%, about 60%, about 70%, about 80%, about 90%, or about 100% compared to the increase observed in an untreated subject identified as having a mutation in the PKP2 gene.

[0097] Various other aspects and embodiments are disclosed in the detailed description that follows. The invention is limited solely by the appended claims.

BRIEF DESCRIPTION OF FIGURES

[0098] FIG. 1 shows a diagram illustrating a non-limiting example of a vector genome. The full polynucleotide sequence of the vector genome is SEQ ID NO: 12. The expression cassette is SEQ ID NO: 8. The MHCK7 promoter as described herein is labelled "Enhancer/MHCK7" in the diagram.

[0099] FIG. 2 shows a diagram illustrating a non-limiting example of a vector genome. The full polynucleotide sequence of the vector genome is SEQ ID NO: 13. The expression cassette is SEQ ID NO: 9.

[0100] FIG. 3 shows a diagram illustrating a non-limiting example of a vector genome. The full polynucleotide sequence of the vector genome is SEQ ID NO: 14. The expression cassette is SEQ ID NO: 10. The MHCK7 promoter as described herein is labelled "Enhancer/MHCK7" in the diagram.

[0101] FIG. 4 shows a diagram illustrating a non-limiting example of a vector genome. The full polynucleotide sequence of the vector genome is SEQ ID NO: 15. The expression cassette is SEQ ID NO: 11.

[0102] FIGS. 5A-5B show PKP2 protein expression in transduced differentiated AC16 cells. FIG. 5A shows Western Blots (WB) of PKP2 (top panel) or loading control, GAPDH (bottom panel). FIG. 5B show a bar graph of the Western Blot. The AAV vector serotype (AAV9 or rh74) and the promoter (MHCK7 or hTnT) are noted. Controls included a GFP vector (CON-GFP) and no transduction (No Tdxn).

[0103] FIGS. 6A-6D show left ventricle ejection fraction percentage (LVEF %) for normal mice (left bars), untreated PKP2 knockout mice (middle bars, cKO PKP2), or treated mice (right bars). FIG. 6A shows results with the AAV9 vector and MHCK7 promoter (AAV9-MHCK7). FIG. 6B shows results with the AAVrh.74 vector and MHCK7 promoter (AAVrh.74-MHCK7). FIG. 6C shows results with the AAV9 vector and hTnT promoter (AAV9-hTnT). FIG. 6D shows results with the AAVrh.74 vector and hTnT promoter (AAVrh.74-hTnT).

[0104] FIGS. 7A-7D show left ventricle fractional shortening percentage (FS %) for normal mice (left bars), untreated PKP2 knockout mice (middle bars, cKO PKP2), or treated mice (right bars). FIG. 7A shows results with the AAV9 vector and MHCK7 promoter (AAV9-MHCK7). FIG. 7B shows results with the AAVrh.74 vector and MHCK7 promoter (AAVrh.74-MHCK7). FIG. 7C shows results with the AAV9 vector and hTnT promoter (AAV9-hTnT). FIG. 7D shows results with the AAVrh.74 vector and the hTnT promoter (AAVrh.74-hTnT).

[0105] FIGS. 8A-8D show right ventricle area in millimeters squared (RV Area (mm.sup.2)) for normal mice (left bars), untreated PKP2 knockout mice (middle bars, cKO PKP2), or treated mice (right bars). FIG. 8A shows results with the AAV9 vector and MHCK7 promoter (AAV9-MHCK7). FIG. 8B shows results with the AAVrh.74 vector and MHCK7 promoter (AAVrh.74-MHCK7). FIG. 8C shows results with the AAV9 vector and hTnT promoter (AAV9-hTnT). FIG. 8D shows results with the AAVrh.74 vector and hTnT promoter (AAVrh.74-hTnT).

[0106] FIGS. 9A-9D show right ventricle velocity time integral in millimeters per second (RV VTI (mm/sec)) for normal mice (left bars), untreated PKP2 knockout mice (middle bars, cKO PKP2), or treated mice (right bars). FIG. 9A shows results with the AAV9 vector and MHCK7 promoter (AAV9-MHCK7). FIG. 9B shows results with the AAVrh.74 vector and MHCK7 promoter (AAVrh.74-MHCK7). FIG. 9C shows results with the AAV9 vector and hTnT promoter (AAV9-hTnT). FIG. 9D shows results with the AAVrh.74 vector and hTnT promoter (AAVrh.74-hTnT).

[0107] FIGS. 10A-10B illustrate the degree of fibrosis in left and right ventricles based on quantitation of the Percent Collagen following trichrome histological staining of the heart. Control animals without the conditional PKP2 gene knock-out (Cre Neg group) were found to have very little collagen, while control PKP2 knock-out animals receiving Formulation Buffer (CKO FB group) were found to have substantially greater proportion of collagen in both left and right ventricles. AAV-mediated overexpression of PKP2 resulted in robust attenuation of collagen, to varying degrees, in all AAV-injected groups [n=4 for all groups; p-values reflect results from One-way ANOVA with Bonferroni post-hoc analyses]. FIG. 10A is a bar graph of percent collagen in the left ventricle. FIG. 10B is a bar graph of percent collagen in the right ventricle.

[0108] FIG. 11 shows a diagram illustrating a non-limiting example of a vector genome. The full polynucleotide sequence of the vector genome is SEQ ID NO: 89. The expression cassette is SEQ ID NO: 93. The MHCK7 promoter as described herein is labelled "Enhancer/MHCK7" in the diagram.

[0109] FIG. 12 shows a diagram illustrating a non-limiting example of a vector genome. The full polynucleotide sequence of the vector genome is SEQ ID NO: 90. The expression cassette is SEQ ID NO: 94.

[0110] FIG. 13 shows a diagram illustrating a non-limiting example of a vector genome. The full polynucleotide sequence of the vector genome is SEQ ID NO: 91. The expression cassette is SEQ ID NO: 95. The MHCK7 promoter as described herein is labelled "Enhancer/MHCK7" in the diagram.

[0111] FIG. 14 shows a diagram illustrating a non-limiting example of a vector genome. The full polynucleotide sequence of the vector genome is SEQ ID NO: 92. The expression cassette is SEQ ID NO: 96.

DETAILED DESCRIPTION OF THE INVENTION

[0112] The present disclosure provided gene therapy vectors for PKP2 that deliver a polynucleotide encoding a PKP2 polypeptide or a functional variant thereof, along with methods of use, and other compositions and methods. In particular embodiments, the disclosure relates to a gene therapy vector comprising a promoter sequence operatively linked to a polynucleotide encoding a PKP2 polypeptide or a functional variant thereof. In some embodiments, the promoter is a Myosin Heavy-chain Creatine Kinase 7 (MHCK7) promoter. In some embodiment, the AAV vector is an AAV9 vector. In some embodiments, the promoter is an MHCK7 promoter and the AAV vector is an AAV9 vector. In some embodiments, the promoter is a hTNNT2 promoter. In some embodiment, the promoter is an hTNNT2 promoter and the AAV vector is an AAV9 vector. In some embodiments, the PKP2 is human PKP2a. In some embodiments, the PKP2 is human PKP2b. In some embodiment, the AAV vector is an rh74 vector. In some embodiments, the promoter is an MHCK7 promoter and the AAV vector is an rh74 vector. In some embodiments, the promoter is a hTNNT2 promoter. In some embodiment, the promoter is an hTNNT2 promoter and the AAV vector is an rh74 vector. In some embodiments, the PKP2 is human PKP2a. In some embodiments, the PKP2 is human PKP2b.

[0113] This disclosure further provides methods of treating a disorder or disorder in a subject by administering a gene therapy vector of the disclosure to the subject. In a certain embodiment, the disorder or disorder is arrhythmogenic right ventricular cardiomyopathy (ARVC).

[0114] In certain embodiments, the subject being treated is an ARVC patient having one or more mutation in a PKP2 gene. More than half of ARVC patients carry mutations in the desmosomal gene PKP2 encoding the protein Plakophilin-2 (PKP2). PKP2 is also associated with Brugada syndrome (BrS) and idiopathic ventricular fibrillation. It is a member of the armadillo repeat and plakophilin protein family. The protein contains nine central, conserved armadillo repeat domains flanked by N-terminal and C-terminal domains. It functions to link cadherins to intermediate filaments in the cytoskeleton

[0115] Plakophilin 2 localizes to cell desmosomes and nuclei and binds plakoglobin, desmoplakin, and the desmosomal cadherins via an N-terminal head domain. PKP2 provides a lateral stabilizing force with the desmosomal-intermediate filament assembly facilitating cell-to-cell contact. It may also serve roles in intracellular signaling regulation, electrophysiologic and trafficking regulation, and control of transcription processes.

[0116] Intravenous injection of an AAV9 vector encoding a C-terminal deletion mutant of PKP2a (R735X) in the heart of wild-type mice accelerates the appearance of ARVC when treated mice are subjected to exercise training. Cruz et al. J Am Coll Cardiol. 65(14):1438-50 (2015). Mutant PKP2a causes a disease phenotype; and control AAV9 vector expressing the non-mutant PKP2a causes no phenotypic change in wild type mice. Heterologous expression of wild-type human PKP2a does not induce disease or altered function. These studies demonstrate that mutant PKP2a can cause a disease phenotype. They fail to demonstrate a curative role for PKP2, because heterologous expression of non-mutant PKP2 resulted in no phenotypic change in the wild-type mouse.

[0117] In accordance with the present invention, a polynucleotide encoding a PKP2 or functional variant thereof, wherein the PKP2 or functional variant thereof comprises at least 800 or at least 830 amino acids (e.g., no C terminal truncation at Arg-735), may be employed in generating a gene therapy vector. The resulting vector may be employed in treating diseases or disorders, e.g. a PKP2-related disease or disorder, e.g. ARVC, Brugada syndrome (BrS), idiopathic ventricular fibrillation, dilated cardiomyopathy (DCM), and others.

[0118] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains. Although methods and materials similar or equivalent to those described herein can be used in the practice of the present invention, suitable methods and materials are described below. All publications, patent applications, patents, and other references mentioned herein are expressly incorporated by reference in their entirety. In cases of conflict, the present specification, including definitions, will control. In addition, the materials, methods, and examples described herein are illustrative only and are not intended to be limiting.

[0119] All publications and patents mentioned herein are hereby incorporated by reference in their entirety as if each individual publication or patent was specifically and individually indicated to be incorporated by reference. In case of conflict, the present application, including any definitions herein, will control. However, mention of any reference, article, publication, patent, patent publication, and patent application cited herein is not, and should not be taken as an acknowledgment, or any form of suggestion, that they constitute valid prior art or form part of the common general knowledge in any country in the world.

[0120] In the present description, any concentration range, percentage range, ratio range, or integer range is to be understood to include the value of any integer within the recited range and, when appropriate, fractions thereof (such as one tenth and one hundredth of an integer), unless otherwise indicated. The term "about", when immediately preceding a number or numeral, means that the number or numeral ranges plus or minus 10%. It should be understood that the terms "a" and "an" as used herein refer to "one or more" of the enumerated components unless otherwise indicated. The use of the alternative (e.g., "or") should be understood to mean either one, both, or any combination thereof of the alternatives. The term "and/or" should be understood to mean either one, or both of the alternatives. As used herein, the terms "include" and "comprise" are used synonymously.

[0121] As used herein, the terms "identity" and "identical" refer, with respect to a polypeptide or polynucleotide sequence, to the percentage of exact matching residues in an alignment of that "query" sequence to a "subject" sequence, such as an alignment generated by the BLAST algorithm. Identity is calculated, unless specified otherwise, across the full length of the subject sequence. Thus a query sequence "shares at least x % identity to" a subject sequence if, when the query sequence is aligned to the subject sequence, at least x % (rounded down) of the residues in the subject sequence are aligned as an exact match to a corresponding residue in the query sequence. Where the subject sequence has variable positions (e.g., residues denoted X), an alignment to any residue in the query sequence is counted as a match. Sequence alignments may be performed using the NCBI Blast service (BLAST+ version 2.12.0).

[0122] As used herein, the term "operatively linked" refers to a functional relationship between two or more nucleic acid (e.g., DNA) segments. Typically, it refers to the functional relationship of a transcriptional regulatory sequence to a transcribed sequence. For example, a promoter sequence is operatively linked to a coding sequence if it stimulates or modulates the transcription of the coding sequence in an appropriate host cell or other expression system. Generally, promoter transcriptional regulatory sequences that are operatively linked to a transcribed sequence are physically contiguous to the transcribed sequence, i.e., they are cis-acting. However, some transcriptional regulatory sequences, such as enhancers, need not be physically contiguous or located in close proximity to the coding sequences whose transcription they enhance.

[0123] As used herein, an "AAV vector" or "rAAV vector" refers to a recombinant vector comprising one or more polynucleotides of interest (or transgenes) that are flanked by AAV inverted terminal repeat sequences (ITRs). Such AAV vectors can be replicated and packaged into infectious viral particles when present in a host cell that has been transfected with a plasmid encoding and expressing rep and cap gene products. Alternatively, AAV vectors can be packaged into infectious particles using a host cell that has been stably engineered to express rep and cap genes.

[0124] As used herein, an "AAV virion" or "AAV viral particle" or "AAV vector particle" refers to a viral particle composed of at least one AAV capsid protein and an encapsidated polynucleotide AAV vector. As used herein, if the particle comprises a heterologous polynucleotide (i.e., a polynucleotide other than a wild-type AAV genome such as a transgene to be delivered to a mammalian cell), it is typically referred to as an "AAV vector particle" or simply an "AAV vector." Thus, production of AAV vector particle necessarily includes production of AAV vector, as such a vector is contained within an AAV vector particle.

[0125] As used herein, "promoter" refers to a polynucleotide sequence capable of promoting initiation of RNA transcription from a polynucleotide in a eukaryotic cell.

[0126] As used herein, "vector genome" refers to the polynucleotide sequence packaged by the vector (e.g., an rAAV virion), including flanking sequences (in AAV, inverted terminal repeats). The terms "expression cassette" and "polynucleotide cassette" refer to the portion of the vector genome between the flanking ITR sequences. "Expression cassette" implies that the vector genome comprises at least one gene encoding a gene product operatively linked to an element that drives expression (e.g., a promoter).

[0127] As used herein, the term "patient in need" or "subject in need" refers to a patient or subject at risk of, or suffering from, a disease, disorder or condition that is amenable to treatment or amelioration with a recombinant gene therapy vector or gene editing system disclosed herein. A patient or subject in need may, for instance, be a patient or subject diagnosed with a disorder associated with heart. A subject may have a mutation in an PKP2 gene or deletion of all or a part of PKP2 gene, or of gene regulatory sequences, that causes aberrant expression of the PKP2 protein. "Subject" and "patient" are used interchangeably herein. The subject treated by the methods described herein may be an adult or a child. Subjects may range in age.

[0128] As used herein, the term "variant" refers to a protein that has one or more amino-acid substitution, insertion, or deletion as compared to a parental protein. As used herein, the term "functional variant" refers to a protein that has one or more amino-acid substitution, insertion, or deletion as compared to a parental protein, and which retains one or more desired activities of the parental protein.

[0129] As used herein, "treating" refers to ameliorating one or more symptoms of a disease or disorder. The term "preventing" refers to delaying or interrupting the onset of one or more symptoms of a disease or disorder or slowing the progression of PKP2-related disease or disorder, e.g., arrhythmogenic right ventricular cardiomyopathy (ARVC).

[0130] Adeno-associated virus (AAV) is a replication-deficient parvovirus, the single-stranded DNA genome of which is about 4.7 kb in length including two .about.145-nucleotide inverted terminal repeat (ITRs). There are multiple known variants of AAV, also sometimes called serotypes when classified by antigenic epitopes. The nucleotide sequences of the genomes of the AAV serotypes are known. For example, the complete genome of AAV-1 is provided in GenBank Accession No. NC_002077; the complete genome of AAV-2 is provided in GenBank Accession No. NC_001401 and Srivastava et al., J. Virol., 45: 555-564 (1983); the complete genome of AAV-3 is provided in GenBank Accession No. NC_1829; the complete genome of AAV-4 is provided in GenBank Accession No. NC_001829; the AAV-5 genome is provided in GenBank Accession No. AF085716; the complete genome of AAV-6 is provided in GenBank Accession No. NC_00 1862; at least portions of AAV-7 and AAV-8 genomes are provided in GenBank Accession Nos. AX753246 and AX753249, respectively; the AAV-9 genome is provided in Gao et al., J. Virol., 78: 6381-6388 (2004); the AAV-10 genome is provided in Mol. Ther., 13(1): 67-76 (2006); and the AAV-11 genome is provided in Virology, 330(2): 375-383 (2004). The sequence of the AAVrh.74 genome is provided in U.S. Pat. No. 9,434,928, incorporated herein by reference. Cis-acting sequences directing viral DNA replication (rep), encapsidation/packaging and host cell chromosome integration are contained within the AAV ITRs. Three AAV promoters (named p5, p19, and p40 for their relative map locations) drive the expression of the two AAV internal open reading frames encoding rep and cap genes. The two rep promoters (p5 and p19), coupled with the differential splicing of the single AAV intron (at nucleotides 2107 and 2227), result in the production of four rep proteins (rep78, rep68, rep52, and rep40) from the rep gene. Rep proteins possess multiple enzymatic properties that are ultimately responsible for replicating the viral genome. The cap gene is expressed from the p40 promoter and it encodes the three capsid proteins VP1, VP2, and VP3. Alternative splicing and non-consensus translational start sites are responsible for the production of the three related capsid proteins. A single consensus polyadenylation site is located at map position 95 of the AAV genome. The life cycle and genetics of AAV are reviewed in Muzyczka, Current Topics in Microbiology and Immunology, 158: 97-129 (1992).

[0131] AAV possesses unique features that make it attractive as a vector for delivering foreign DNA to cells, for example, in gene therapy. AAV infection of cells in culture is noncytopathic, and natural infection of humans and other animals is silent and asymptomatic. Moreover, AAV infects many mammalian cells allowing the possibility of targeting many different tissues in vivo. Moreover, AAV transduces slowly dividing and non-dividing cells, and can persist essentially for the lifetime of those cells as a transcriptionally active nuclear episome (extrachromosomal element). The AAV proviral genome is inserted as cloned DNA in plasmids, which makes construction of recombinant genomes feasible. Furthermore, because the signals directing AAV replication and genome encapsidation are contained within the ITRs of the AAV genome, some or all of the internal approximately 4.3 kb of the genome (encoding replication and structural capsid proteins, rep-cap) may be replaced with foreign DNA. To generate AAV vectors, the rep and cap proteins may be provided in trans. Another significant feature of AAV is that it is an extremely stable and hearty virus. It easily withstands the conditions used to inactivate adenovirus (56.degree. to 65.degree. C. for several hours), making cold preservation of AAV less critical. AAV may even be lyophilized. Finally, AAV-infected cells are not resistant to superinfection.

[0132] Gene delivery viral vectors useful in the practice of the present invention can be constructed utilizing methodologies well known in the art of molecular biology. Typically, viral vectors carrying transgenes are assembled from polynucleotides encoding the transgene, suitable regulatory elements and elements necessary for production of viral proteins, which mediate cell transduction. Such recombinant viruses may be produced by techniques known in the art, e.g., by transfecting packaging cells or by transient transfection with helper plasmids or viruses. Typical examples of virus packaging cells include but are not limited to HeLa cells, SF9 cells (optionally with a baculovirus helper vector), 293 cells, etc. A Herpesvirus-based system can be used to produce AAV vectors, as described in US20170218395A1. Detailed protocols for producing such replication-defective recombinant viruses may be found for instance in WO95/14785, WO96/22378, U.S. Pat. Nos. 5,882,877, 6,013,516, 4,861,719, 5,278,056 and WO94/19478, the complete contents of each of which is hereby incorporated by reference.

[0133] The present disclosure contemplates compositions and methods of use related to Plakophilin-2 (PKP2) proteins or polypeptides. Various mutations in PKP2 are known to be associated with cardiomyopathy and heart failure, including diseases like those described in van Tintelen et al. Circulation 113:1650-58 (2006); Novelli Front. Cardiovasc. Med. (2008); and in other sources. Viral vector-mediated delivery of the PKP2 gene may therefore serve as a viable therapeutic for PKP2-related human diseases such as cardiomyopathy and heart failure.

[0134] More than 230 mutations in the PKP2 gene have been identified in people with arrhythmogenic right ventricular cardiomyopathy (ARVC). (See "PKP2 gene," MedlinePlus). This condition most commonly affects the myocardium surrounding the right ventricle, one of the two lower chambers of the heart. ARVC increases the risk of an abnormal heartbeat (arrhythmia) and sudden death. Some PKP2 gene mutations lead to the production of an abnormally short version of plakophilin 2. Other mutations alter the structure of plakophilin 2 by adding, deleting, or changing one or more of its protein building blocks (amino acids). Studies suggest that the altered protein impairs the formation and function of desmosomes.

[0135] Without normal desmosomes, cells of the myocardium detach from one another and die, particularly when the heart muscle is placed under stress (such as during vigorous exercise). The damaged myocardium is gradually replaced by fat and scar tissue. As this abnormal tissue builds up, the walls of the right ventricle become stretched out, preventing the heart from pumping blood effectively. These changes also disrupt the electrical signals that control the heartbeat, which can lead to arrhythmia. Description of PKP2-related disease may be found in the following references: Bonne et al. Genomics 51:452-454 (1998) [PubMed: 9721216]; Bonne et al. Cytogenet. Cell Genet. 88:286-287 (2000) [PubMed: 10828611]; Dalal et al., Circulation 113:1641-1649 (2006) [PubMed: 16549640]; Gerull et al. Nature Genet. 36:1162-1164 (2004 [PubMed: 15489853]; Grossmann et al. J. Cell Biol. 167:149-160 (2004) [PubMed: 15479741]; Marcus et al. Circulation 65:384-398 (1982) [PubMed: 7053899]; and Mertens et al. J. Cell Biol. 135:1009-1025 (1996) [PubMed: 8922383]. See also OMIM.org entry 602861 ("PLAKOPHILIN 2; PKP2").

[0136] The native sequences of human PKP2a and its isoform PKP2b are shown below, with Arg-735 underlined:

TABLE-US-00001 PKP2a-837 amino acids (SEQ ID NO: 1) 1 MAAPGAPAEY GYIRTVLGQQ ILGQLDSSSL ALPSEAKLKL 41 AGSSGRGGQT VKSLRIQEQV QQTLARKGRS SVGNGNLHRT 81 SSVPEYVYNL HLVENDFVGG RSPVPKTYDM LKAGTTATYE 121 GRWGRGTAQY SSQKSVEERS LRHPLRRLEI SPDSSPERAH 161 YTHSDYQYSQ RSQAGHTLHH QESRRAALLV PPRYARSEIV 201 GVSRAGTTSR QRHFDTYHRQ YQHGSVSDTV FDSIPANPAL 241 LTYPRPGTSR SMGNLLEKEN YLTAGLTVGQ VRPLVPLQPV 281 TQNRASRSSW HQSSFHSTRT LREAGPSVAV DSSGRRAHLT 321 VGQAAAGGSG NLLTERSTFT DSQLGNADME MTLERAVSML 361 EADHMLPSRI SAAATFIQHE CFQKSEARKR VNQLRGILKL 401 LQLLKVQNED VQRAVCGALR NLVFEDNDNK LEVAELNGVP 441 RLLQVLKQTR DLETKKQITG LLWNLSSNDK LKNLMITEAL 481 LTLTENIIIP FSGWPEGDYP KANGLLDFDI FYNVTGCLRN 521 MSSAGADGRK AMRRCDGLID SLVHYVRGTI ADYQPDDKAT 561 ENCVCILHNL SYQLEAELPE KYSQNIYIQN RNIQTDNNKS 601 IGCFGSRSRK VKEQYQDVPM PEEKSNPKGV EWLWHSIVIR 641 MYLSLIAKSV RNYTQEASLG ALQNLTAGSG PMPTSVAQTV 681 VQKESGLQHT RKMLHVGDPS VKKTAISLLR NLSRNLSLQN 721 EIAKETLPDL 7SIIPDTVPS TDLLIETTAS ACYTLNNIIQ 761 NSYQNARDLL NTGGIQKIMA ISAGDAYASN KASKAASVLL 801 YSLWAHTELH HAYKKAQFKK TDFVNSRTAK AYHSLKD PKP2b-881 amino acids (SEQ ID NO: 2) 1 MAAPGAPAEY GYIRTVLGQQ ILGQLDSSSL ALPSEAKLKL 41 AGSSGRGGQT VKSLRIQEQV QQTLARKGRS SVGNGNLHRT 81 SSVPEYVYNL HLVENDFVGG RSPVPKTYDM LKAGTTATYE 121 GRWGRGTAQY SSQKSVEERS LRHPLRRLEI SPDSSPERAH 161 YTHSDYQYSQ RSQAGHTLHH QESRRAALLV PPRYARSEIV 201 GVSRAGTTSR QRHFDTYHRQ YQHGSVSDTV FDSIPANPAL 241 LTYPRPGTSR SMGNLLEKEN YLTAGLTVGQ VRPLVPLQPV 281 TQNRASRSSW HQSSFHSTRT LREAGPSVAV DSSGRRAHLT 321 VGQAAAGGSG NLLTERSTFT DSQLGNADME MTLERAVSML 361 EADHMLPSRI SAAATFIQHE CFQKSEARKR VNQLRGILKL 401 LQLLKVQNED VQRAVCGALR NLVFEDNDNK LEVAELNGVP 441 RLLQVLKQTR DLETKKQITD HTVNLRSRNG WPGAVAHACN 481 PSTLGGQGGR ITRSGVRDQP DQHGLLWNLS SNDKLKNLMI 521 TEALLTLTEN IIIPFSGWPE GDYPKANGLL DFDIFYNVTG 561 CLRNMSSAGA DGRKAMRRCD GLIDSLVHYV RGTIADYQPD 601 DKATENCVCI LHNLSYQLEA ELPEKYSQNI YIQNRNIQTD 641 NNKSIGCFGS RSRKVKEQYQ DVPMPEEKSN PKGVEWLWHS 681 IVIRMYLSLI AKSVRNYTQE ASLGALQNLT AGSGPMPTSV 721 AQTVVQKESG LQHTRKMLHV GDPSVKKTAI SLLRNLSRNL 761 SLQNEIAKET LPDLVSIIPD TVPSTDLLIE TTASACYTLN 801 NIIQNSYQNA RDLLNTGGIQ KIMAISAGDA YASNKASKAA 841 SVLLYSLWAH TELHHAYKKA QFKKTDFVNS RTAKAYHSLK 881 D

[0137] One experimental model of PKP2-related disease is the R735X model, as described in Cruz et al. J Am Coll Cardiol 65:1438-50 (2015). R735X is numbered according to the PKP2b isoform. The R735X mutant of PKP2a is 690 amino acids in length, due to C-terminal truncation at Arg-690, (Arg-735 relative to PKP2b, SEQ ID NO: 2).

[0138] In some embodiments, the PKP2 protein comprises a polypeptide sequence at least 75%, 80%, 85%, 90%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to any one of SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, the PKP2 protein is a wild-type or native PKP2 protein, e.g. human PKP2a or human PKP2b.

[0139] In some embodiments, the disclosure provides a recombinant adeno-associated virus (rAAV) virion, comprising a capsid and a vector genome, wherein the vector genome comprises a polynucleotide sequence encoding an PKP2 or a functional variant thereof, operatively linked to a promoter. In some embodiments, the disclosure provides a recombinant adeno-associated virus (rAAV) virion, comprising a capsid and a vector genome, wherein the vector genome comprises a polynucleotide sequence encoding an PKP2, operatively linked to a promoter. The polynucleotide encoding the PKP2a may comprise a polynucleotide sequence at least 75%, 80%, 85%, 90%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 3.

[0140] The polynucleotide encoding the PKP2b may comprise a polynucleotide sequence at least 75%, 80%, 85%, 90%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 4.

[0141] Optionally, the polynucleotide sequence encoding the vector genome may comprise a Kozak sequence, including but not limited to GCCACCATGG (SEQ ID NO: 5). Kozak sequence may overlap the polynucleotide sequence encoding an PKP2a protein or a functional variant thereof. For example, the vector genome may comprise a polynucleotide sequence (with first ten nucleotides constituting the Kozak sequence) at least 75%, 80%, 85%, 90%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 6.

[0142] Kozak sequence may overlap the polynucleotide sequence encoding an PKP2b protein or a functional variant thereof. For example, the vector genome may comprise a polynucleotide sequence (with first ten nucleotides constituting the Kozak sequence) at least 75%, 80%, 85%, 90%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 7.

[0143] In some embodiments, the Kozak sequence is an alternative Kozak sequence comprising or consisting of any one of:

TABLE-US-00002 (SEQ ID NO: 16) (gcc)gccRccAUGG; AGNNAUGN; ANNAUGG; ANNAUGC; ACCAUGG; and (SEQ ID NO: 18) GACACCAUGG.

[0144] In some embodiments, the vector genome comprises no Kozak sequence.

[0145] The polynucleotide sequence may be codon-optimized. For example, the vector genome may comprise a polynucleotide sequence encoding a PKP2a that shares at least 75%, 80%, 85%, 90%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to SEQ ID NO: 87.

[0146] The vector genome may comprise a polynucleotide sequence encoding a PKP2b that shares at least 75%, 80%, 85%, 90%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to SEQ ID NO: 88.

[0147] The AAV virions of the disclosure comprise a vector genome. The vector genome may comprise an expression cassette (or a polynucleotide cassette for gene-editing applications not requiring expression of the polynucleotide sequence). Any suitable inverted terminal repeats (ITRs) may be used. The ITRs may be AAV ITRs from the same serotype as the capsid present in the AAV virion, or a different serotype from the capsid (e.g., AAV2 ITRs may be used with an AAV virion having an AAV9 capsid or an AAVrh74 capsid). In each case, the serotype of the capsid determines the name applied to the virion. The ITR are generally the most 5' and most 3' elements of the vector genome. The vector genome will also generally contain, in 5' to 3' order, a promoter, a transgene, 3' untranslated region (UTR) sequences (e.g., a WPRE element), and a polyadenylation sequence. In variations, the vector genome includes an enhancer element (generally 5' to the promoter) and/or an exon (generally 3' to the promoter). In variations, the vector genomes of the disclosure encode a partial or complete transgene sequence used as a repair template in a gene editing system. In such variations, the vector genome may comprise an exogenous promoter, or the gene editing system may insert the transgene into a locus in the genome having an endogenous promoter, such as a cardiac- or myocyte-specific promoter.

[0148] In some embodiments, the 5' ITR comprises a polynucleotide sequence at least 75%, 80%, 85%, 90%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 20.

[0149] In some embodiments, the 5' ITR comprises a polynucleotide sequence at least 75%, 80%, 85%, 90%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 21.

[0150] In some embodiments, the 5' ITR comprises a polynucleotide sequence at least 75%, 80%, 85%, 90%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 22)

[0151] In some embodiments, the 5' ITR comprises a polynucleotide sequence at least 75%, 80%, 85%, 90%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 23.

[0152] In some embodiments, the 3' ITR comprises a polynucleotide sequence at least 75%, 80%, 85%, 90%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 24.

[0153] In some embodiments, the 3' ITR comprises a polynucleotide sequence at least 75%, 80%, 85%, 90%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 25.

[0154] In some embodiments, the 3' ITR comprises a polynucleotide sequence at least 75%, 80%, 85%, 90%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 26.

[0155] In some embodiments the vector genome comprises one or more filler sequences, e.g., at least 75%, 80%, 85%, 90%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 27; SEQ ID NO: 28; or SEQ ID NO: 29.

[0156] In some embodiments, the polynucleotide sequence encoding an PKP2 protein or functional variant thereof is operatively linked to a promoter. In certain embodiments, the promoter is an MHCK7 promoter. In certain embodiments, the promoter is an TNNT2 promoter.

[0157] The present disclosure contemplates use of various promoters. Promoters useful in embodiments of the present disclosure include, without limitation, a cytomegalovirus (CMV) promoter, phosphoglycerate kinase (PGK) promoter, or a promoter sequence comprised of the CMV enhancer and portions of the chicken beta-actin promoter and the rabbit beta-globin gene (CAG). In some cases, the promoter may be a synthetic promoter. Exemplary synthetic promoters are provided by Schlabach et al. PNAS USA. 107(6):2538-43 (2010). In some embodiments, the promoter comprises a polynucleotide sequence at least 75%, 80%, 85%, 90%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 30.

[0158] In some embodiments, a polynucleotide sequence encoding an PKP2 protein or functional variant thereof is operatively linked to an inducible promoter. An inducible promoter may be configured to cause the polynucleotide sequence to be transcriptionally expressed or not transcriptionally expressed in response to addition or accumulation of an agent or in response to removal, degradation, or dilution of an agent. The agent may be a drug. The agent may be tetracycline or one of its derivatives, including, without limitation, doxycycline. In some cases, the inducible promoter is a tet-on promoter, a tet-off promoter, a chemically-regulated promoter, a physically-regulated promoter (i.e., a promoter that responds to presence or absence of light or to low or high temperature). Inducible promoters include heavy metal ion inducible promoters (such as the mouse mammary tumor virus (mMTV) promoter or various growth hormone promoters), and the promoters from T7 phage which are active in the presence of T7 RNA polymerase. This list of inducible promoters is non-limiting.

[0159] In some cases, the promoter is a tissue-specific promoter, such as a promoter capable of driving expression in a cardiac cell to a greater extent than in a non-cardiac cell. In some embodiments, tissue-specific promoter is a selected from any various cardiac cell-specific promoters including but not limited to, desmin (Des), alpha-myosin heavy chain (.alpha.-MHC), myosin light chain 2 (MLC-2), cardiac troponin C (cTnC), cardiac troponin T (hTNNT2), muscle creatine kinase (CK) and combinations of promoter/enhancer regions thereof, such as MHCK7. In some cases, the promoter is a ubiquitous promoter. A "ubiquitous promoter" refers to a promoter that is not tissue-specific under experimental or clinical conditions. In some cases, the ubiquitous promoter is any one of Cytomegalovirus (CMV), Cytomegalovirus early enhancer element chicken beta-Actin gene intron with the splice acceptor of the rabbit beta-Globin gene (CAG), ubiquitin C (UBC), Phosphoglycerate Kinase (PGK), Eukaryotic translation elongation factor 1 alpha 1 (EF1-alpha), Glyceraldehyde 3-phosphate dehydrogenase (GAPDH), simian virus 40 (SV40), Hepatitis B virus (HBV), chicken beta-actin, and human beta-actin promoters.

[0160] In some embodiments, the promoter sequence is selected from Table 3. In some embodiments, the promoter comprises a polynucleotide sequence at least 75%, 80%, 85%, 90%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to any one of SEQ ID NOS: 31-51. In some embodiments, the promoter comprises a fragment of a polynucleotide sequence of any one of SEQ ID NOs: 31-51, e.g., a fragment comprising at least 25%, at least 50%, at least 75%, 80%, 85%, 90%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% of any one of SEQ ID NOs: 31-51.

TABLE-US-00003 TABLE 3 SEQ ID PROMOTER SEQUENCE NO: MHCK7 ACCCTTCAGATTAAAAATAACTGAGGTAAGGGCCTGGGTAGG 31 GGAGGTGGTGTGAGACGCTCCTGTCTCTCCTCTATCTGCCCA TCGGCCCTTTGGGGAGGAGGAATGTGCCCAAGGACTAAAAAA AGGCCATGGAGCCAGAGGGGCGAGGGCAACAGACCTTTCATG GGCAAACCTTGGGGCCCTGCTGTCTAGCATGCCCCACTACGG GTCTAGGCTGCCCATGTAAGGAGGCAAGGCCTGGGGACACCC GAGATGCCTGGTTATAATTAACCCAGACATGTGGCTGCCCCC CCCCCCCCAACACCTGCTGCCTCTAAAAATAACCCTGTCCCT GGTGGATCCCCTGCATGCGAAGATCTTCGAACAAGGCTGTGG GGGACTGAGGGCAGGCTGTAACAGGCTTGGGGGCCAGGGCTT ATACGTGCCTGGGACTCCCAAAGTATTACTGTTCCATGTTCC CGGCGAAGGGCCAGCTGTCCCCCGCCAGCTAGACTCAGCACT TAGTTTAGGAACCAGTGAGCAAGTCAGCCCTTGGGGCAGCCC ATACAAGGCCATGGGGCTGGGCAAGCTGCACGCCTGGGTCCG GGGTGGGCACGGTGCCCGGGCAACGAGCTGAAAGCTCATCTG CTCTCAGGGGCCCCTCCCTGGGGACAGCCCCTCCTGGCTAGT CACACCCTGTAGGCTCCTCTATATAACCCAGGGGCACAGGGG CTGCCCTCATTCTACCACCACCTCCACAGCACAGACAGACAC TCAGGAGCCAGCCAG Human cardiac CTCAGTCCATTAGGAGCCAGTAGCCTGGAAGATGTCTTTACC 33 troponin T CCCAGCATCAGTTCAAGTGGAGCAGCACATAACTCTTGCCCT promoter CTGCCTTCCAAGATTCTGGTGCTGAGACTTATGGAGTGTCTT (without GGAGGTTGCCTTCTGCCCCCCAACCCTGCTCCCAGCTGGCCC exon 1) TCCCAGGCCTGGGTTGCTGGCCTCTGCTTTATCAGGATTCTC hTnnT2/ AAGAGGGACAGCTGGTTTATGTTGCATGACTGTTCCCTGCAT HTNNT2 ATCTGCTCTGGTTTTAAATAGCTTATCTGAGCAGCTGGAGGA CCACATGGGCTTATATGGCGTGGGGTACATGTTCCTGTAGCC TTGTCCCTGGCACCTGCCAAAATAGCAGCCAACACCCCCCAC CCCCACCGCCATCCCCCTGCCCCACCCGTCCCCTGTCGCACA TTCCTCCCTCCGCAGGGCTGGCTCACCAGGCCCCAGCCCACA TGCCTGCTTAAAGCCCTCTCCATCCTCTGCCTCACCCAGT Human cardiac CTCAGTCCATTAGGAGCCAGTAGCCTGGAAGATGTCTTTACC 32 troponin T CCCAGCATCAGTTCAAGTGGAGCAGCACATAACTCTTGCCCT promoter (with CTGCCTTCCAAGATTCTGGTGCTGAGACTTATGGAGTGTCTT exon 1, GGAGGTTGCCTTCTGCCCCCCAACCCTGCTCCCAGCTGGCCC underlined) TCCCAGGCCTGGGTTGCTGGCCTCTGCTTTATCAGGATTCTC hTnnT2/ AAGAGGGACAGCTGGTTTATGTTGCATGACTGTTCCCTGCAT HTNNT2 ATCTGCTCTGGTTTTAAATAGCTTATCTGAGCAGCTGGAGGA CCACATGGGCTTATATGGCGTGGGGTACATGTTCCTGTAGCC TTGTCCCTGGCACCTGCCAAAATAGCAGCCAACACCCCCCAC CCCCACCGCCATCCCCCTGCCCCACCCGTCCCCTGTCGCACA TTCCTCCCTCCGCAGGGCTGGCTCACCAGGCCCCAGCCCACA TGCCTGCTTAAAGCCCTCTCCATCCTCTGCCTCACCCAGTCC CCGCTGAGACTGAGCAGACGCCTCCAGGATCTGTCGGCAG Mouse .alpha.- GGTACCGGATCCTGCAAGGTCACACAAGGGTCTCCACCCACC 34 cardiac myosin AGGTGCCCTAGTCTCAATTTCAGTTTCCATGCCTTGTTCTCA heavy chain CAATGCTGGCCTCCCCAGAGCTAATTTGGACTTTGTTTTTAT promoter TTCAAAAGGGCCTGAATGAGGAGTAGATCTTGTGCTACCCAG (.alpha.MHC) CTCTAAGGGTGCCCGTGAAGCCCTCAGACCTGGAGCCTTTGC AACAGCCCTTTAGGTGGAAGCAGAATAAAGCAATTTTCCTTA AAGCCAAAATCCTGCCTCTAGACTCTTCTTCTCTGACCTCGG TCCCTGGGCTCTAGGGTGGGGAGGTGGGGCTTGGAAGAAGAA GGTGGGGAAGTGGCAAAAGCCGATCCCTAGGGCCCTGTGAAG TTCGGAGCCTTCCCTGTACAGCACTGGCTCATAGATCCTCCT CCAGCCAAACATAGCAAGAAGTGATACCTCCTTTGTGACTTC CCCAGGCCCAGTACCTGTCAGGTTGAAACAGGATTTAGAGAA GCCTCTGAACTCACCTGAACTCTGAAGCTCATCCACCAAGCA AGCACCTAGGTGCCACTGCTAGTTAGTATCCTACGCTGATAA TATGCAGAGCTGGGCCACAGAAGTCCTGGGGTGTAGGAACTG ACCAGTGACTTTTCAGTCGGCAAAGGTATGACCCCCTCAGCA GATGTAGTAATGTCCCCTTAGATCCCATCCCAGGCAGGTCTC TAAGAGGACATGGGATGAGAGATGTAGTCATGTGGCATTCCA AACACAGCTATCCACAGTGTCCCTTGCCCCTTCCACTTAGCC AGGAGGACAGTAACCTTAGCCTATCTTTCTTCCTCCCCATCC TCCCAGGACACACCCCCTGGTCTGCAGTATTCATTTCTTCCT TCACGTCCCCTCTGTGACTTCCATTTGCAAGGCTTTTGACCT CTGCAGCTGCTGGAAGATAGAGTTTGGCCCTAGGTGTGGCAA GCCATCTCAAGAGAAAGCAGACAACAGGGGGACCAGATTTTG GAAGGATCAGGAACTAAATCACTGGCGGGCCTGGGGGTAGAA AAAAGAGTGAGTGAGTCCGCTCCAGCTAAGCCAAGCTAGTCC CCGAGATACTCTGCCACAGCTGGGCTGCTCGGGGTAGCTTTA GGAATGTGGGTCTGAAAGACAATGGGATTGGAAGACATCTCT TTGAGTCTCCCCTCAACCCCACCTACAGACACACTCGTGTGT GGCCAGACTCCTGTTCAACAGCCCTCTGTGTTCTGACCACTG AGCTAGGCAACCAGAGCATGGGCCCTGTGCTGAGGATGAAGA GTTGGTTACCAATAGCAAAAACAGCAGGGGAGGGAGAACAGA GAACGAAATAAGGAAGGAAGAAGGAAAGGCCAGTCAATCAGA TGCAGTCAGAAGAGATGGGAAGCCAACACACAGCTTGAGCAG AGGAAACAGAAAAGGGAGAGATTCTGGGCATAAGGAGGCCAC AGAAAGAAGAGCCCAGGCCCCCCAAGTCTCCTCTTTATACCC TCATCCCGTCTCCCAATTAAGCCCACTCTTCTTCCTAGATCA GACCTGAGCTGCAGCGAAGAGACCCGTAGGGAGGATCACACT GGATGAAGGAGATGTGTGGAGAAGTCCAGGGAACCTAAGAGC CAGAGCCTAAAAGAGCAAGAGATAAAGGTGCTTCAAAGGTGG CCAGGCTGTGCACACAGAGGGTCGAGGACTGGTGGTAGAGCC TCAAGATAAGGATGATGCTCAGAATGGGCGGGGGGGGGGATT CTGGGGGGGGGAGAGAGAAGGTGAGAAGGAGCCTGGAACAGA GAATCTGGAAGCGCTGGAAACGATACCATAAAGGGAAGAACC CAGGCTACCTTTAGATGTAAATCATGAAAGACAGGGAGAAGG GAAGCTGGAGAGAGTAGAAGGACCCCGGGGCAAGACATTGAA GCAAGGACAAGCCAGGTTGAGCGCTCCGTGAAATCAGCCTGC TGAAGGCAGAGCCCTGGTATGAGCACCAGAACAGCAGAGGCT AGGGTTAATGTCGAGACAGGGAACAGAAGGTAGACACAGGAA CAGACAGAGACGGGGGAGCCAGGTAACAAAGGAATGGTCCTT CTCACCTGTGGCCAGAGCGTCCATCTGTGTCCACATACTCTA GAATGTTCATCAGACTGCAGGGCTGGCTTGGGAGGCAGCTGG AAAGAGTATGTGAGAGCCAGGGGAGACAAGGGGGCCTAGGAA AGGAAGAAGAGGGCAAACCAGGCCACACAAGAGGGCAGAGCC CAGAACTGAGTTAACTCCTTCCTTGTTGCATCTTCCATAGGA GGCAGTGGGAACTCTGTGACCACCATCCCCCATGAGCCCCCA CTACCCATACCAAGTTTGGCCTGAGTGGCATTCTAGGTTCCC TGAGGACAGAGCCTGGCCTTTGTCTCTTGGACCTGACCCAAG CTGACCCAATGTTCTCAGTACCTTATCATGCCCTCAAGAGCT TGAGAACCAGGCAGTGACATATTAGGCCATGGGCTAACCCTG GAGCTTGCACACAGGAGCCTCAAGTGACCTCCAGGGACACAG CTGCAGACAGGTGGCCTTTATCCCCAAAGAGCAACCATTTGG CATAGGTGGCTGCAAATGGGAATGCAAGGTTGAATCAGGTCC CTTCAAGAATACTGCATGCAAGACCTAAGACCCCTGGAGAGA GGGGTATGCTCCTGCCCCCACCCACCATAAGGGGAGTGAACT ATCCTAGGGGGCTGGCGACCTTGGGGAGACACCACATTACTG AGAGTGCTGAGCCCAGAAAAACTGACCGCCCTGTGTCCTGCC CACCTCCACACTCTAGAGCTATATTGAGAGGTGACAGTAGAT AGGGTGGGAGCTGGTAGCAGGGAGAGTGTTCCTGGGTGTGAG GGTGTAGGGGAAAGCCAGAGCAGGGGAGTCTGGCTTTGTCTC CTGAACACAATGTCTACTTAGTTATAACAGGCATGACCTGCT AAAGACCCAACATCTACGACCTCTGAAAAGACAGCAGCCCTG GAGGACAGGGGTTGTCTCTGAGCCTTGGGTGCTTGATGGTGC CACAAAGGAGGGCATGAGTGTGAGTATAAGGCCCCAGGAGCG TTAGAGAAGGGCACTTGGGAAGGGGTCAGTCTGCAGAGCCCC TATCCATGGAATCTGGAGCCTGGGGCCAACTGGTGTAAATCT CTGGGCCTGCCAGGCATTCAAAGCAGCACCTGCATCCTCTGG CAGCCTGGGGAGGCGGAAGGGAGCAACCCCCCACTTATACCC TTTCTCCCTCAGCCCCAGGATTAACACCTCTGGCCTTCCCCC TTCCCACCTCCCATCAGGAGTGGAGGGTTGCAGAGGGAGGGT AAAAACCTACATGTCCAAACATCATGGTGCACGATATATGGA TCAGTATGTGTAGAGGCAAGAAAGGAAATCTGCAGGCTTAAC TGGGTTAATGTGTAAAGTCTGTGTGCATGTGTGTGTGTCTGA CTGAAAACGGGCATGGCTGTGCAGCTGTTCAGTTCTGTGCGT GAGGTTACCAGACTGCAGGTTTGTGTGTAAATTGCCCAAGGC AAAGTGGGTGAATCCCTTCCATGGTTTAAAGAGATTGGATGA TGGCCTGCATCTCAAGGACCATGGAAAATAGAATGGACACTC TATATGTGTCTCTAAGCTAAGGTAGCAAGGTCTTTGGAGGAC ACCTGTCTAGAGATGTGGGCAACAGAGACTACAGACAGTATC TGTACAGAGTAAGGAGAGAGAGGAGGGGGTGTAGAATTCTCT TACTATCAAAGGGAAACTGAGTCGTGCACCTGCAAAGTGGAT GCTCTCCCTAGACATCATGACTTTGTCTCTGGGGAGCCAGCA CTGTGGAACTTCAGGTCTGAGAGAGTAGGAGGCTCCCCTCAG CCTGAAGCTATGCAGATAGCCAGGGTTGAAAGGGGGAAGGGA GAGCCTGGGATGGGAGCTTGTGTGTTGGAGGCAGGGGACAGA TATTAAGCCTGGAAGAGAAGGTGACCCTTACCCAGTTGTTCA ACTCACCCTTCAGATTAAAAATAACTGAGGTAAGGGCCTGGG TAGGGGAGGTGGTGTGAGACGCTCCTGTCTCTCCTCTATCTG CCCATCGGCCCTTTGGGGAGGAGGAATGTGCCCAAGGACTAA AAAAAGGCCATGGAGCCAGAGGGGCGAGGGCAACAGACCTTT CATGGGCAAACCTTGGGGCCCTGCTGTCCTCCTGTCACCTCC AGAGCCAAGGGATCAAAGGAGGAGGAGCCAGGACAGGAGGGA AGTGGGAGGGAGGGTCCCAGCAGAGGACTCCAAATTTAGGCA GCAGGCATATGGGATGGGATATAAAGGGGCTGGAGCACTGAG AGCTGTCAGAGATTTCTCCAACCCAGGTAAGAGGGAGTTTCG GGTGGGGGCTCTTCACCCACACCAGACCTCTCCCCACCTAGA AGGAAACTGCCTTTCCTGGAAGTGGGGTTCAGGCCGGTCAGA GATCTGACAGGGTGGCCTTCCACCAGCCTGGGAAGTTCTCAG TGGCAGGAGGTTTCCACAAGAAACACTGGATGCCCCTTCCCT TACGCTGTCTTCTCCATCTTCCTCCTGGGGATGCTCCTCCCC GTCTTGGTTTATCTTGGCTCTTCGTCTTCAGCAAGATTTGCC CTGTGCTGTCCACTCCATCTTTCTCTACTGTCTCCGTGCCTT GCCTTGCCTTCTTGCGTGTCCTTCCTTTCCACCCATTTCTCA CTTCACCTTTTCTCCCCTTCTCATTTGTATTCATCCTTCCTT CCTTCCTTCCTTCCTTCCTTCCTTCCTTCCTTCCTTCCTTTC TCCCTTCCTTCCTTCCTTCCTTCCTTCCTTCCTTCCTTCCTT CCTGTGTCAGAGTGCTGAGAATCACACCTGGGGTTCCCACCC TTATGTAAACAATCTTCCAGTGAGCCACAGCTTCAGTGCTGC TGGGTGCTCTCTTACCTTCCTCACCCCCTGGCTTGTCCTGTT CCATCCTGGTCAGGATCTCTAGATTGGTCTCCCAGCCTCTGC TACTCCTCTTCCTGCCTGTTCCTCTCTCTGTCCAGCTGCGCC ACTGTGGTGCCTCGTTCCAGCTGTGGTCCACATTCTTCAGGA TTCTCTGAAAAGTTAACCAGGTGAGAATGTTTCCCCTGTAGA CAGCAGATCACGATTCTCCCGGAAGTCAGGCTTCCAGCCCTC TCTTTCTCTGCCCAGCTGCCCGGCACTCTTAGCAAACCTCAG GCACCCTTACCCCACATAGACCTCTGACAGAGAAGCAGGCAC TTTACATGGAGTCCTGGTGGGAGAGCCATAGGCTACGGTGTA AAAGAGGCAGGGAAGTGGTGGTGTAGGAAAGTCAGGACTTCA CATAGAAGCCTAGCCCACACCAGAAATGACAGACAGATCCCT CCTATCTCCCCCATAAGAGTTTGAGTCGACCCGCGGCCCCGA ATTG Chicken cardiac GGGATAAAAGCAGTCTGGGCTTTCACATGACAGCATCTGGGG 35 troponin T CTGCGGCAGAGGGTCGGGTCCGAAGCGCTGCCTTATCAGCGT promoter CCCCAGCCCTGGGAGGTGACAGCTGGCTGGCTTGTGTCAGCC (cTnT) CCTCGGGCACTCACGTATCTCCGTCCGACGGGTTTAAAATAG CAAAACTCTGAGGCCACACAATAGCTTGGGCTTATATGGGCT CCTGTGGGGGAAGGGGGAGCACGGAGGGGGCCGGGGCCGCTG CTGCCAAAATAGCAGCTCACAAGTGTTGCATTCCTCTCTGGG CGCCGGGCACATTCCTGCTGGCTCTGCCCGCCCCGGGGTGGG CGCCGGGGGGACCTTAAAGCCTCTGCCCCCCAAGGAGCCCTT CCCAGACAGCCGCCGGCACCCACCGCTCCGTGGGA Human Creatine CTCTCAGCCCTGGAAGTCCTTGCTCACAGCCGAGGCGCCGAG 36 Kinase M AGCGCTTGCTCTGCCCAGATCTGCGCGAGTCTGGCGCCCGCG (hCKM) CTCTGAACGGCGTCGCTGCCCAGCCCCCTTCCCCGGGAGGTG GGAGCGGCCACCCAGGGCCCCGTGGCTGCCCTTGTAAGGAGG CGAGGCCCGAGGACACCCGAGACGCCCGGTTATAATTAACCA GGACACGTGGCGAACCCCCCTCCAACACCTGCCCCCGAACCC CCCCATACCCAGCGCCTCGGGTCTCGGCCTTTGCGGCAGAGG AGACAGCAAAGCGCCCTCTAAAAATAACTCCTTTCCCGGCGA CCGAGACCCTCCCTGTCCCCCGCACAGCGGAAATCTCCCAGT GGCACCGAGGGGGCGAGGGTTAAGTGGGGGGGAGGGTGACCA CCGCCTCCCACCCTTGCCCTGAGTTTGAATCTCTCCAACTCA GCCAGCCTCAGTTTCCCCTCCACTCAGTCCCTAGGAGGAAGG GGCGCCCAAGCGCGGGTTTCTGGGGTTAGACTGCCCTCCATT GCAATTGGTCCTTCTCCCGGCCTCTGCTTCCTCCAGCTCACA GGGTATCTGCTCCTCCTGGAGCCACACCTTGGTTCCCCGAGG TGCCGCTGGGACTCGGGTAGGGGTGAGGGCCCAGGGGGCACA GGGGGAGCCGAGGGCCACAGGAAGGGCTGGTGGCTGAAGGAG ACTCAGGGGCCAGGGGACGGTGGCTTCTACGTGCTTGGGACG TTCCCAGCCACCGTCCCATGTTCCCGGCGGGGGGCCAGCTGT CCCCACCGCCAGCCCAACTCAGCACTTGGTCAGGGTATCAGC TTGGTGGGGGGGCGTGAGCCCAGCCCCTGGGGCGGCTCAGCC CATACAAGGCCATGGGGCTGGGCGCAAAGCATGCCTGGGTTC AGGGTGGGTATGGTGCGGGAGCAGGGAGGTGAGAGGCTCAGC TGCCCTCCAGAACTCCTCCCTGGGGACAACCCCTCCCAGCCA ATAGCACAGCCTAGGTCCCCCTATATAAGGCCACGGCTGCTG GCCCTTCCTTTGGGTCAGTGTCACCTCCAGGATACAGACA Human beta- GCCCAGCACCCCAAGGCGGCCAACGCCAAAACTCTCCCTCCT 37 actin (HuBa) CCTCTTCCTCAATCTCGCTCTCGCTCTTTTTTTTTTTCGCAA AAGGAGGGGAGAGGGGGTAAAAAAATGCTGCACTGTGCGGCG AAGCCGGTGAGTGAGCGGCGCGGGGCCAATCAGCGTGCGCCG TTCCGAAAGTTGCCTTTTATGGCTCGAGCGGCCGCGGCGGCG CCCTATAAAACCCAGCGGCGCGACGCGCCACCACCGCCGAGT C Chicken beta- GGTCGAGGTGAGCCCCACGTTCTGCTTCACTCTCCCCATCTC 38 actin (CBA) CCCCCCCTCCCCACCCCCAATTTTGTATTTATTTATTTTTTA GGTCGAGGTGAGCCCCACGTTCTGCTTCACTCTCCCCATCTC CCCCCCCTCCCCACCCCCAATTTTGTATTTATTTATTTTTTA ATTATTTTGTGCAGCGATGGGGGCGGGGGGGGGGGGGGCGCG CGCCAGGCGGGGCGGGGCGGGGCGAGGGGCGGGGCGGGGCGA GGCGGAGAGGTGCGGCGGCAGCCAATCAGAGCGGCGCGCTCC GAAAGTTTCCTTTTATGGCGAGGCGGCGGCGGCGGCGGCCCT ATAAAAAGCGAAGCGCGCGGCGGGCGGGA Cytomegalovirus TGGTGATGCGGTTTTGGCAGTACACCAATGGGCGTGGATAGC 39 (CMV) GGTTTGACTCACGGGGATTTCCAAGTCTCCACCCCATTGACG TGGTGATGCGGTTTTGGCAGTACACCAATGGGCGTGGATAGC GGTTTGACTCACGGGGATTTCCAAGTCTCCACCCCATTGACG TCAATGGGAGTTTGTTTTGGCACCAAAATCAACGGGACTTTC CAAAATGTCGTAATAACCCCGCCCCGTTGACGCAAATGGGCG GTAGGCGTGTACGGTGGGAGGTCTATATAAGCAGAGCTCGTT TAGTGAACCG Cytomegalovirus TAGTTATTAATAGTAATCAATTACGGGGTCATTAGTTCATAG 40

(CMV) CCCATATATGGAGTTCCGCGTTACATAACTTACGGTAAATGG (second CCCGCCTGGCTGACCGCCCAACGACCCCCGCCCATTGACGTC version) AATAATGACGTATGTTCCCATAGTAACGCCAATAGGGACTTT CCATTGACGTCAATGGGTGGAGTATTTACGGTAAACTGCCCA CTTGGCAGTACATCAAGTGTATCATATGCCAAGTACGCCCCC TATTGACGTCAATGACGGTAAATGGCCCGCCTGGCATTATGC CCAGTACATGACCTTATGGGACTTTCCTACTTGGCAGTACAT CTACGTATTAGTCATCGCTATTACCATGGTGATGCGGTTTTG GCAGTACATCAATGGGCGTGGATAGCGGTTTGACTCACGGGG ATTTCCAAGTCTCCACCCCATTGACGTCAATGGGAGTTTGTT TTGGCACCAAAATCAACGGGACTTTCCAAAATGTCGTAACAA CTCCGCCCCATTGACGCAAATGGGCGGTAGGCGTGTACGGTG GGAGGTCTATATAAGCAGAGCTGGTTTAGTGAACCGT Cytomegalovirus CGTTACATAACTTACGGTAAATGGCCCGCCTGGCTGACCGCC 41 (CMV) (third CAACGACCCCCGCCCATTGACGTCAATAATGACGTATGTTCC version) CATAGTAACGCCAATAGGGACTTTCCATTGACGTCAATGGGT GGAGTATTTACGGTAAACTGCCCACTTGGCAGTACATCAAGT GTATCATATGCCAAGTACGCCCCCTATTGACGTCAATGACGG TAAATGGCCCGCCTGGCATTATGCCCAGTACATGACCTTATG GGACTTTCCTACTTGGCAGTACATCTACGTATTAGTCATCGC TATTACCATGGTGATGCGGTTTTGGCAGTACATCAATGGGCG TGGATAGCGGTTTGACTCACGGGGATTTCCAAGTCTCCACCC CATTGACGTCAATGGGAGTTTGTTTTGGCACCAAAATCAACG GGACTTTCCAAAATGTCGTAACAACTCCGCCCCATTGACGCA AATGGGCGGTAGGCGTGTACGGTGGGAGGTCTATATAAGCAG AGCT CAG promoter ACTTACGGTAAATGGCCCGCCTGGCTGACCGCCCAACGACCC 42 (first version) CCGCCCATTGACGTCAATAATGACGTATGTTCCCATAGTAAC GCCAATAGGGACTTTCCATTGACGTCAATGGGTGGAGTATTT ACGGTAAACTGCCCACTTGGCAGTACATCAAGTGTATCATAT GCCAAGTACGCCCCCTATTGACGTCAATGACGGTAAATGGCC CGCCTGGCATTATGCCCAGTACATGACCTTATGGGACTTTCC TACTTGGCAGTACATCTACGTATTAGTCATCGCTATTACCAT GGTCGAGGTGAGCCCCACGTTCTGCTTCACTCTCCCCATCTC CCCCCCCTCCCCACCCCCAATTTTGTATTTATTTATTTTTTA ATTATTTTGTGCAGCGATGGGGGCGGGGGGGGGGGGGGCGCG CGCCAGGCGGGGCGGGGCGGGGCGAGGGGCGGGGCGGGGCGA GGCGGAGAGGTGCGGCGGCAGCCAATCAGAGCGGCGCGCTCC GAAAGTTTCCTTTTATGGCGAGGCGGCGGCGGCGGCGGCCCT ATAAAAAGCGAAGCGCGCGGCGGGCGG CAG promoter CGTTACATAACTTACGGTAAATGGCCCGCCTGGCTGACCGCC 43 (second CAACGACCCCCGCCCATTGACGTCAATAATGACGTATGTTCC version) CATAGTAACGCCAATAGGGACTTTCCATTGACGTCAATGGGT GGAGTATTTACGGTAAACTGCCCACTTGGCAGTACATCAAGT GTATCATATGCCAAGTACGCCCCCTATTGACGTCAATGACGG TAAATGGCCCGCCTGGCATTATGCCCAGTACATGACCTTATG GGACTTTCCTACTTGGCAGTACATCTACGTATTAGTCATCGC TATTACCATGTCGAGGTGAGCCCCACGTTCTGCTTCACTCTC CCCATCTCCCCCCCCTCCCCACCCCCAATTTTGTATTTATTT ATTTTTTAATTATTTTGTGCAGCGATGGGGGCGGGGGGGGGG GGGGCGCGCGCCAGGCGGGGCGGGGCGGGGCGAGGGGCGGGG CGGGGCGAGGCGGAGAGGTGCGGCGGCAGCCAATCAGAGCGG CGCGCTCCGAAAGTTTCCTTTTATGGCGAGGCGGCGGCGGCG GCGGCCCTATAAAAAGCGAAGCGCGCGGCGGGCG Human EF1- CAACCTTTGGAGCTAAGCCAGCAATGGTAGAGGGAAGATTCT 44 alpha (EF1-.alpha.) GCACGTCCCTTCCAGGCGGCCTCCCCGTCACCACCCCCCCCA ACCCGCCCCGACCGGAGCTGAGAGTAATTCATACAAAAGGAC TCGCCCCTGCCTTGGGGAATCCCAGGGACCGTCGTTAAACTC CCACTAACGTAGAACCCAGAGATCGCTGCGTTCCCGCCCCCT CACCCGCCCGCTCTCGTCATCACTGAGGTGGAGAATAGCATG CGTGAGGCTCCGGTGCCCGTCAGTGGGCAGAGCGCACATCGC CCACAGTCCCCGAGAAGTTGGGGGGAGGGGTCGGCAATTGAA CGGGTGCCTAGAGAAGGTGGCGCGGGGTAAACTGGGAAAGTG ATGTCGTGTACTGGCTCCGCCTTTTTCCCGAGGGTGGGGGAG AACCGTATATAAGTGCAGTAGTCGCCGTGAACGTT Human ACTTGTGGACAAAGTTTGCTCTATTCCACCTCCTCCAGGCCC 48 CamKIIa TCCTTGGGTCCATCACCCCAGGGGTGCTGGGTCCATCCCACC (CaMKIIa) CCCAGGCCCACACAGGCTTGCAGTATTGTGTGCGGTATGGTC AGGGCGTCCGAGAGCAGGTTTCGCAGTGGAAGGCAGGCAGGT GTTGGGGAGGCAGTTACCGGGGCAACGGGAACAGGGCGTTTT GGAGGTGGTTGCCATGGGGACCTGGATGCTGACGAAGGCTCG CGAGGCTGTGAGCAGCCACAGTGCCCTGC

[0161] In a certain embodiment, the vector genome comprises a polynucleotide sequence at least 75%, 80%, 85%, 90%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 31. In a certain embodiment, the vector genome comprises a polynucleotide sequence at least 75%, 80%, 85%, 90%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 32. In a certain embodiment, the vector genome comprises a polynucleotide sequence at least 75%, 80%, 85%, 90%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to SEQ ID NO: 33.

[0162] Further illustrative examples of promoters are the SV40 late promoter from simian virus 40, the Baculovirus polyhedron enhancer/promoter element, Herpes Simplex Virus thymidine kinase (HSV tk), the immediate early promoter from cytomegalovirus (CMV) and various retroviral promoters including LTR elements. A large variety of other promoters are known and generally available in the art, and the sequences of many such promoters are available in sequence databases such as the GenBank database.

[0163] In some cases, vectors of the present disclosure further comprise one or more regulatory elements selected from the group consisting of an enhancer, an intron, a poly-A signal, a 2A peptide encoding sequence, a WPRE (Woodchuck hepatitis virus posttranscriptional regulatory element), and a HPRE (Hepatitis B posttranscriptional regulatory element).

[0164] In some embodiments, the vector comprises a CMV enhancer.

[0165] In certain embodiments, the vectors comprise one or more enhancers. In particular embodiments, the enhancer is a CMV enhancer sequence, a GAPDH enhancer sequence, a (3-actin enhancer sequence, or an EF1-.alpha. enhancer sequence. Sequences of the foregoing are known in the art. For example, the sequence of the CMV immediate early (IE) enhancer is SEQ ID NO: 50.

[0166] In certain embodiments, the vectors comprise one or more introns. In particular embodiments, the intron is a rabbit globin intron sequence, a chicken .beta.-actin intron sequence, a synthetic intron sequence, an SV40 intron, or an EF1-.alpha. intron sequence.

[0167] In certain embodiments, the vectors comprise a polyA sequence. In particular embodiments, the polyA sequence is a rabbit globin polyA sequence, a human growth hormone polyA sequence, a bovine growth hormone polyA sequence, a PGK polyA sequence, an SV40 polyA sequence, or a TK polyA sequence. In some embodiments, the poly-A signal may be a bovine growth hormone polyadenylation signal (bGHpA).

[0168] In certain embodiments, the vectors comprise one or more transcript stabilizing element. In particular embodiments, the transcript stabilizing element is a WPRE sequence, a HPRE sequence, a scaffold-attachment region, a 3' UTR, or a 5' UTR. In particular embodiments, the vectors comprise both a 5' UTR and a 3' UTR.

[0169] In some embodiments, the vector comprises a 5' untranslated region (UTR) selected from Table 4. In some embodiments, the vector genome comprises a polynucleotide sequence at least 75%, 80%, 85%, 90%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to any one of SEQ ID NOS 51-61.

TABLE-US-00004 TABLE 4 5' SEQ UNTRANSLATED ID REGION SEQUENCE NO: Human beta-actin CGCGTCCGCCCGCGAGCACAGAGCCTCGCCTTTGCCGATC 51 exon/intron CGCCGCCCGTCCACACCCGCCGCCAGGTAAGCCCGGCCAG CCGACCGGGGCATGCGGCCGCGGCCCTTCGCCCGTGCAGA GCCGCCGTCTGGGCCGCAGCGGGGGGCGCATGGGGCGGAA CCGGACCGCCGTGGGGGGCGCGGGAGAAGCCCCTGGGCCT CCGGAGATGGGGGACACCCCACGCCAGTTCGCAGGCGCGA GGCCGCGCTCGGGCGGGCGCGCTCCGGGGGTGCCGCTCTC GGGGCGGGGGCAACCGGCGGGGTCTTTGTCTGAGCCGGGC TCTTGCCAATGGGGATCGCACGGTGGGCGCGGCGTAGCCC CCGTCAGGCCCGGTGGGGGCTGGGGCGCCATGCGCGTGCG CGCTGGTCCTTTGGGCGCTAACTGCGTGCGCGCTGGGAAT TGGCGCTAATTGCGCGTGCGCGCTGGGACTCAATGGCGCT AATCGCGCGTGCGTTCTGGGGCCCGGGCGCTTGCGCCACT TCCTGCCCGAGCCGCTGGCGCCCGAGGGTGTGGCCGCTGC GTGCGCGCGCGCGACCCGGTCGCTGTTTGAACCGGGCGGA GGCGGGGCTGGCGCCCGGTTGGGAGGGGGTTGGGGCCTGG CTTCCTGCCGCGCGCCGCGGGGACGCCTCCGACCAGTGTT TGCCTTTTATGGTAATAACGCGGCCGGCCCGGCTTCCTTT GTCCCCAATCTGGGCGCGCGCCGGCGCCCCCTGGCGGCCT AAGGACTCGGCGCGCCGGAAGTGGCCAGGGCGGCAGCGGC TGCTCTTGGCGGCCCCGAGGTGACTATAGCCTTCTTTTGT GTCTTGATAGTTCGCCAGCCTCTGCTAACCATGTTCATGC CTTCTTCTTTTTCCTACAGCTCCTGGGCAACGTGCTGGTT ATTGTGCTGTCTCATCATTTTGGCAAAGAATTC Chicken beta-actin GTCGCTGCGCGCTGCCTTCGCCCCGTGCCCCGCTCCGCCG 52 exon/intron + rabbit CCGCCTCGCGCCGCCCGCCCCGGCTCTGACTGACCGCGTT globin intron ACTCCCACAGGTGAGCGGGCGGGACGGCCCTTCTCCTCCG GGCTGTAATTAGCGCTTGGTTTAATGACGGCTTGTTTCTT TTCTGTGGCTGCGTGAAAGCCTTGAGGGGCTCCGGGAGGG CCCTTTGTGCGGGGGGAGCGGCTCGGGGGGTGCGTGCGTG TGTGTGTGCGTGGGGAGCGCCGCGTGCGGCTCCGCGCTGC CCGGCGGCTGTGAGCGCTGCGGGCGCGGCGCGGGGCTTTG TGCGCTCCGCAGTGTGCGCGAGGGGAGCGCGGCCGGGGGC GGTGCCCCGCGGTGCGGGGGGGGCTGCGAGGGGAACAAAG GCTGCGTGCGGGGTGTGTGCGTGGGGGGGTGAGCAGGGGG TGTGGGCGCGTCGGTCGGGCTGCAACCCCCCCTGCACCCC CCTCCCCGAGTTGCTGAGCACGGCCCGGCTTCGGGTGCGG GGCTCCGTACGGGGCGTGGCGCGGGGCTCGCCGTGCCGGG CGGGGGGTGGCGGCAGGTGGGGGTGCCGGGCGGGGCGGGG CCGCCTCGGGCCGGGGAGGGCTCGGGGGAGGGGCGCGGCG GCCCCCGGAGCGCCGGCGGCTGTCGAGGCGCGGCGAGCCG CAGCCATTGCCTTTTATGGTAATCGTGCGAGAGGGCGCAG GGACTTCCTTTGTCCCAAATCTGTGCGGAGCCGAAATCTG GGAGGCGCCGCCGCACCCCCTCTAGCGGGCGCGGGGCGAA GCGGTGCGGCGCCGGCAGGAAGGAAATGGGCGGGGAGGGC CTTCGTGCGTCGCCGCGCCGCCGTCCCCTTCTCCCTCTCC AGCCTCGGGGCTGTCCGCGGGGGGACGGCTGCCTTCGGGG GGGACGGGGCAGGGCGGGGTTCGGCTTCTGGCGTGTGACC GGCGGCTCTAGAGCCTCTGCTAACCATGTTCATGCCTTCT TCTTTTTCCTACAGCTCCTGGGCAACGTGCTGGTTATTGT GCTGTCTCATCATTTTGGCAAAGAATTC SV40 intron GGTAAGTTTAGTCTTTTTGTCTTTTATTTCAGGTCCCGGA 53 (Chimeric intron TCCGGTGGTGGTGCAAATCAAAGAACTGCTCCTCAGTGGA sequence) TGTTGCCTTTACTTCTAGGCCTGTACGGAAGTGTTACTTC Shown in FIG. 14 TGCTCTAAAAGCTGCGGAATTGTACCCGC 5'UTR-Syn1 Hs AGTCTGCGGTGGGCAGCGGAGGAGTCGTGTCGTGCCTGAG 54 AGCGCAGCTGTGCTCCTGGGCACCGCGCAGTCCGCCCCCG CGGCTCCTGGCCAGACCACCCCTAGGACCCCCTGCCCCAA GTCGCA CMV IE exon TCAGATCGCCTGGAGAGGCCATCCACGCTGTTTTGACCTC 55 CATAGTGGACACCGGGACCGATCCAGCCTCCGCGGCCGGG AACGGTGCATTGGAACGCGGATTCCCCGTGCCAAGAGTGA C TPL-ePKP2 CTCACTCTCTTCCGCATCGCTGTCTGCGAGGGCCAGCTGT 56 (adenovirus derived TGGGCTCGCGGTTGAGGACAAACTCTTCGCGGTCTTTCCA enhancer element) GTACTCTTGGATCGGAAACCCGTCGGCCTCCGAACGGTAC TCCGCCACCGAGGGACCTGAGCGAGTCCGCATCGACCGGA TCGGAAAACCTCTCGAGAAAGGCGTCTAACCAGTCACAGT CGCAAGGTAGGCTGAGCACCGTGGCGGGCGGCAGCGGGTG GCGGTCGGGGTTGTTTCTGGCGGAGGTGCTGCTGATGATG TAATTAAAGTAGGCGGTCTTGAGACGGCGGATGGTCGAGG TGAGGTGTGGCAGGCTTGAGATCCAGCTGTTGGGGTGAGT ACTCCCTCTCAAAAGCGGGCATTACTTCTGCGCTAAGATT GTCAGTTTCCAAAAACGAGGAGGATTTGATATTCACCTGG CCCGATCTGGCCATACACTTGAGTGACAATGACATCCACT TTGCCTTTCTCTCCACAGGTGTCCACTCCCAG Human EF1-.alpha. CTTTTTCGCAACGGGTTTGCCGCCAGAACACAGGTAAGTG 57 intron/exon CCGTGTGTGGTTCCCGCGGGCCTGGCCTCTTTACGGGTTA TGGCCCTTGCGTGCCTTGAATTACTTCCACCTGGCTCCAG TACGTGATTCTTGATCCCGAGCTGGAGCCAGGGGCGGGCC TTGCGCTTTAGGAGCCCCTTCGCCTCGTGCTTGAGTTGAG GCCTGGCCTGGGCGCTGGGGCCGCCGCGTGCGAATCTGGT GGCACCTTCGCGCCTGTCTCGCTGCTTTCGATAAGTCTCT AGCCATTTAAAATTTTTGATGACGTGCTGCGACGCTTTTT TTCTGGCAAGATAGTCTTGTAAATGCGGGCCAGGATCTGC ACACTGGTATTTCGGTTTTTGGGCCCGCGGCCGGCGACGG GGCCCGTGCGTCCCAGCGCACATGTTCGGCGAGGCGGGGC CTGCGAGCGCGGCCACCGAGAATCGGACGGGGGTAGTCTC AAGCTGGCCGGCCTGCTCTGGTGCCTGGCCTCGCGCCGCC GTGTATCGCCCCGCCCTGGGCGGCAAGGCTGGCCCGGTCG GCACCAGTTGCGTGAGCGGAAAGATGGCCGCTTCCCGGCC CTGCTCCAGGGGGCTCAAAATGGAGGACGCGGCGCTCGGG AGAGCGGGCGGGTGAGTCACCCACACAAAGGAAAAGGGCC TTTCCGTCCTCAGCCGTCGCTTCATGTGACTCCACGGAGT ACCGGGCGCCGTCCAGGCACCTCGATTAGTTCTGGAGCTT TTGGAGTACGTCGTCTTTAGGTTGGGGGGAGGGGTTTTAT GCGATGGAGTTTCCCCACACTGAGTGGGTGGAGACTGAAG TTAGGCCAGCTTGGCACTTGATGTAATTCTCCTTGGAATT TGGCCTTTTTGAGTTTGGATCTTGGTTCATTCTCAAGCCT CAGACAGTGGTTCAAAGTTTTTTTCTTCCATTTCAG HumanEF1-.alpha., GTAAGTGCCGTGTGTGGTTCCCGCGGGCCTGGCCTCTTTA 58 intron A CGGGTTATGGCCCTTGCGTGCCTTGAATTACTTCCACCTG GCTGCAGTACGTGATTCTTGATCCCGAGCTTCGGGTTGGA AGTGGGTGGGAGAGTTCGAGGCCTTGCGCTTAAGGAGCCC CTTCGCCTCGTGCTTGAGTTGAGGCCTGGCCTGGGCGCTG GGGCCGCCGCGTGCGAATCTGGTGGCACCTTCGCGCCTGT CTCGCTGCTTTCGATAAGTCTCTAGCCATTTAAAATTTTT GATGACCTGCTGCGACGCTTTTTTTCTGGCAAGATAGTCT TGTAAATGCGGGCCAAGATCTGCACACTGGTATTTCGGTT TTTGGGGCCGCGGGCGGCGACGGGGCCCGTGCGTCCCAGC GCACATGTTCGGCGAGGCGGGGCCTGCGAGCGCGGCCACC GAGAATCGGACGGGGGTAGTCTCAAGCTGGCCGGCCTGCT CTGGTGCCTGGCCTCGCGCCGCCGTGTATCGCCCCGCCCT GGGCGGCAAGGCTGGCCCGGTCGGCACCAGTTGCGTGAGC GGAAAGATGGCCGCTTCCCGGCCCTGCTGCAGGGAGCTCA AAATGGAGGACGCGGCGCTCGGGAGAGCGGGCGGGTGAGT CACCCACACAAAGGAAAAGGGCCTTTCCGTCCTCAGCCGT CGCTTCATGTGACTCCACGGAGTACCGGGCGCCGTCCAGG CACCTCGATTAGTTCTCGAGCTTTTGGAGTACGTCGTCTT TAGGTTGGGGGGAGGGGTTTTATGCGATGGAGTTTCCCCA CACTGAGTGGGTGGAGACTGAAGTTAGGCCAGCTTGGCAC TTGATGTAATTCTCCTTGGAATTTGCCCTTTTTGAGTTTG GATCTTGGTTCATTCTCAAGCCTCAGACAGTGGTTCAAAG TTTTTTTCTTCCATTTCAG 5'UTR human TCAGAAGCCCCGGGCTCGTCAGTCAAACCGGTTCTCTGTT 59 CamKIIa TGCACTCGGCAGCACGGGCAGGCAAGTGGTCCCTAGGTTC GGG B-globin intron GTGAGTCTATGGGACCCTTGATGTTTTCTTTCCCCTTCTT 60 TTCTATGGTTAAGTTCATGTCATAGGAAGGGGAGAAGTAA CAGGGTACACATATTGACCAAATCAGGGTAATTTTGCATT TGTAATTTTAAAAAATGCTTTCTTCTTTTAATATACTTTT TTGTTTATCTTATTTCTAATACTTTCCCTAATCTCTTTCT TTCAGGGCAATAATGATACAATGTATCATGCCTCTTTGCA CCATTCTAAAGAATAACAGTGATAATTTCTGGGTTAAGGC AATAGCAATATTTCTGCATATAAATATTTCTGCATATAAA TTGTAACTGATGTAAGAGGTTTCATATTGCTAATAGCAGC TACAATCCAGCTACCATTCTGCTTTTATTTTATGGTTGGG ATAAGGCTGGATTATTCTGAGTCCAAGCTAGGCCCTTTTG CTAATCATGTTCATACCTCTTATCTTCCTCCCACAG SV40 intron (long TCTAGAGGATCCGGTACTCGAGGAACTGAAAAACCAGAAA 61 form; underlined 5' GTTAACTGGTAAGTTTAGTCTTTTTGTCTTTTATTTCAGG and 3' extensions) TCCCGGATCCGGTGGTGGTGCAAATCAAAGAACTGCTCCT CAGTGGATGTTGCCTTTACTTCTAGGCCTGTACGGAAGTG TTACTTCTGCTCTAAAAGCTGCGGAATTGTACCCGC

[0170] In some embodiments, the vector comprises a 3' untranslated region selected from Table 5. In some embodiments, the vector genome comprises a polynucleotide sequence at least 75%, 80%, 85%, 90%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to any one of SEQ ID NOS 62-70.

TABLE-US-00005 TABLE 5 SEQ 3' UNTRANSLATED ID REGION SEQUENCE NO: WPRE(x) (mutated AATCAACCTCTGGATTACAAAATTTGTGAAAGATTGACTG 62 woodchuck hepatitis GTATTCTTAACTATGTTGCTCCTTTTACGCTATGTGGATA regulatory element - CGCTGCTTTAATGCCTTTGTATCATGCTATTGCTTCCCGT version 1) ATGGCTTTCATTTTCTCCTCCTTGTATAAATCCTGGTTGC TGTCTCTTTATGAGGAGTTGTGGCCCGTTGTCAGGCAACG TGGCGTGGTGTGCACTGTGTTTGCTGACGCAACCCCCACT GGTTGGGGCATTGCCACCACCTGTCAGCTCCTTTCCGGGA CTTTCGCTTTCCCCCTCCCTATTGCCACGGCGGAACTCAT CGCCGCCTGCCTTGCCCGCTGCTGGACAGGGGCTCGGCTG TTGGGCACTGACAATTCCGTGGTGTTGTCGGGGAAATCAT CGTCCTTTCCTTGGCTGCTCGCCTGTGTTGCCACCTGGAT TCTGCGCGGGACGTCCTTCTGCTACGTCCCTTCGGCCCTC AATCCAGCGGACCTTCCTTCCCGCGGCCTGCTGCCGGCTC TGCGGCCTCTTCCGCGTCTTCGCCTTCGCCCTCAGACGAG TCGGATCTCCCTTTGGGCCGCCTCCCCGC WPRE(x) (mutated TCAACCTCTGGATTACAAAATTTGTGAAAGATTGACTGGT 63 woodchuck hepatitis ATTCTTAACTATGTTGCTCCTTTTACGCTATGTGGATACG regulatory element - CTGCTTTAATGCCTTTGTATCATGCTATTGCTTCCCGTAT version 2) GGCTTTCATTTTCTCCTCCTTGTATAAATCCTGGTTGCTG TCTCTTTATGAGGAGTTGTGGCCCGTTGTCAGGCAACGTG GCGTGGTGTGCACTGTGTTTGCTGACGCAACCCCCACTGG TTGGGGCATTGCCACCACCTGTCAGCTCCTTTCCGGGACT TTCGCTTTCCCCCTCCCTATTGCCACGGCGGAACTCATCG CCGCCTGCCTTGCCCGCTGCTGGACAGGGGCTCGGCTGTT GGGCACTGACAATTCCGTGGTGTTGTCGGGGAAATCATCG TCCTTTCCTTGGCTGCTCGCCTGTGTTGCCACCTGGATTC TGCGCGGGACGTCCTTCTGCTACGTCCCTTCGGCCCTCAA TCCAGCGGACCTTCCTTCCCGCGGCCTGCTGCCGGCTCTG CGGCCTCTTCCGCGTCTTCGCCTTCGCCCTCAGACGAGTC GGATCTCCCTTTGGGCCGCCTCCCCGCA WPRE(x) (mutated TTCCTGTTAATCAACCTCTGGATTACAAAATTTGTGAAAG 64 woodchuck hepatitis ATTGACTGGTATTCTTAACTATGTTGCTCCTTTTACGCTA regulatory element - TGTGGATACGCTGCTTTAATGCCTTTGTATCATGCTATTG version 3) CTTCCCGTATGGCTTTCATTTTCTCCTCCTTGTATAAATC CTGGTTGCTGTCTCTTTATGAGGAGTTGTGGCCCGTTGTC AGGCAACGTGGCGTGGTGTGCACTGTGTTTGCTGACGCAA CCCCCACTGGTTGGGGCATTGCCACCACCTGTCAGCTCCT TTCCGGGACTTTCGCTTTCCCCCTCCCTATTGCCACGGCG GAACTCATCGCCGCCTGCCTTGCCCGCTGCTGGACAGGGG CTCGGCTGTTGGGCACTGACAATTCCGTGGTGTTGTCGGG GAAGCTGACGTCCTTTCCGCGGCTGCTCGCCTGTGTTGCC ACCTGGATTCTGCGCGGGACGTCCTTCTGCTACGTCCCTT CGGCCCTCAATCCAGCGGACCTTCCTTCCCGCGGCCTGCT GCCGGCTCTGCGGCCTCTTCCGCCTCTTCGCCTTCGCCCT CAGACGAGTCGGATCTCCCTTTGGGCCGCCTCCCCGCCCA TGTATCTTTTTCACCTGTGCCTTGTTTTTGCCTGTGTTCC GCGTCCTACTTTTCAAGCCTCCAAGCTGTGCCTTGGGCGG CTTTGGGGCATGGACATAGATCCCTATAAAGAATTTGGTT CATCTTATCAGTTGTTGAATTTTCTTCCTTTGGAC CAAX TGTGTGATAATG 65 EES CTGTTCTCATCACATCATATCAAGGTTATATACCATCAAT 66 ATTGCCACAGATGTTACTTAGCCTTTTAATATTTCTCTAA TTTAGTGTATATGCAATGATAGTTCTCTGATTTCTGAGAT TGAGTTTCTCATGTGTAATGATTATTTAGAGTTTCTCTTT CATCTGTTCAAATTTTTGTCTAGTTTTATTTTTTACTGAT TTGTAAGACTTCTTTTTATAATCTGCATATTACAATTCTC TTTACTGGGGTGTTGCAAATATTTTCTGTCATTCTATGGC CTGACTTTTCTTAATGGTTTTTTAATTTTAAAAATAAGTC TTAATATTCATGCAATCTAATTAACAATCTTTTCTTTGTG GTTAGGACTTTGAGTCATAAGAAATTTTTCTCTACACTGA AGTCATGATGGCATGCTTCTATATTATTTTCTAAAAGATT TAAAGTTTTGCCTTCTCCATTTAGACTTATAATTCACTGG AATTTTTTTGTGTGTATGGTATGACATATGGGTTCCCTTT TATTTTTTACATATAAATATATTTCCCTGTTTTTCTAAAA AAGAAAAAGATCATCATTTTCCCATTGTAAAATGCCATAT TTTTTTCATAGGTCACTTACATATATCAATGGGTCTGTTT CTGAGCTCTACTCTATTTTATCAGCCTCACTGTCTATCCC CACACATCTCATGCTTTGCTCTAAATCTTGATATTTAGTG GAACATTCTTTCCCATTTTGTTCTACAAGAATATTTTTGT TATTGTCTTTGGGCTTTCTATATACATTTTGAAATGAGGT TGACAAGTTA HPRE ATAACAGGCCTATTGATTGGAAAGTTTGTCAACGAATTGT 67 GGGTCTTTTGGGGTTTGCTGCCCCTTTTACGCAATGTGGA TATCCTGCTTTAATGCCTTTATATGCATGTATACAAGCAA AACAGGCTTTTACTTTCTCGCCAACTTACAAGGCCTTTCT CAGTAAACAGTATATGACCCTTTACCCCGTTGCTCGGCAA CGGCCTGGTCTGTGCCAAGTGTTTGCTGACGCAACCCCCA CTGGTTGGGGCTTGGCCATAGGCCATCAGCGCATGCGTGG AACCTTTGTGTCTCCTCTGCCGATCCATACTGCGGAACTC CTAGCCGCTTGTTTTGCTCGCAGCAGGTCTGGAGCAAACC TCATCGGGACCGACAATTCTGTCGTACTCTCCCGCAAGTA TACATCGTTTCCATGGCTGCTAGGCTGTGCTGCCAACTGG ATCCTGCGCGGGACGTCCTTTGTTTACGTCCCGTCGGCGC TGAATCCCGCGGACGACCCCTCCCGGGGCCGCTTGGGGCT CTACCGCCCGCTTCTCCGTCTGCCGTACCGTCCGACCACG GGGCGCACCTCTCTTTACGCGGACTCCCCGTCTGTGCCTT CTCATCTGCCGGACCGTGTGCACTTCGCTTCACCTCTGCA CGTCGCATGGAGGCCACCGTGAACGCCCACCGGAACCTGC CCAAGGTCTTGCATAAGAGGACTCTTGGACTTTCAGCAAT GTCATC R2V17 (HepB derived TTCCTGTAAACAGGCCTATTGATTGGAAAGTTTGTCAACG 68 enhancer element) AATTGTGGGTCTTTTGGGGTTTGCTGCCCCTTTTACGCAA TGTGGATATCCTGCTTTAATGCCTTTATATGCATGTATAC AAGCAAAACAGGCTTTTACTTTCTCGCCAACTTACAAGGC CTTTCTCAGTAAACAGTATATGACCCTTTACCCCGTTGCT CGGCAACGGCCTGGTCTGTGCCAAGTGTTTGCTGACGCAA CCCCCACTGGTTGGGGCTTGGCCATAGGCCATCAGCGCAT GCGTGGAACCTTTGTGTCTCCTCTGCCGATCCATACTGCG GAACTCCTAGCCGCTTGTTTTGCTCGCAGCTGGACTGGAG CAAACCTCATCGGGACCGACAATTCTGTCGTACTCTCCCG CAAGCACTCACCGTTTCCGCGGCTGCTCGCCTGTGTTGCC ACCTGGATTCTGCGCGGGACGTCCTTCTGCTACGTCCCTT CGGCCCTCAATCCAGCGGACCTTCCTTCCCGCGGCCTGCT GCCGGCTCTGCGGCCTCTTCCGCCTCTTCGCCTTCGCCCT CAGACGAGTCGGATCTCCCTTTGGGCCGCCTCCCCGCCCA TGTATCTTTTTCACCTGTGCCTTGTTTTTGCCTGTGTTCC GCGTCCTACTTTTCAAGCCTCCAAGCTGTGCCTTGGGCGG CTTTGGGGCATGGACATAGATCCCTATAAAGAATTTGGTT CATCTTATCAGTTGTTGAATTTTCTTCCTTTGGAC 3'UTR(globin) GCTGGAGCCTCGGTAGCCGTTCCTCCTGCCCGCTGGGCCT 69 CCCAACGGGCCCTCCTCCCCTCCTTGCACCGGCCCTTCCT GGTCTTTGAATAAA WPRE(r) ATTCGAGCATCTTACCGCCATTTATTCCCATATTTGTTCT 70 GTTTTTCTTGATTTGGGTATACATTTAAATGTTAATAAAA CAAAATGGTGGGGCAATCATTTACATTTTTAGGGATATGT AATTACTAGTTCAGGTGTATTGCCACAAGACAAACATGTT AAGAAACTTTCCCGTTATTTACGCTCTGTTCCTGTTAATC AACCTCTGGATTACAAAATTTGTGAAAGATTGACTGATAT TCTTAACTATGTTGCTCCTTTTACGCTGTGTGGATATGCT GCTTTAATGCCTCTGTATCATGCTATTGCTTCCCGTACGG CTTTCGTTTTCTCCTCCTTGTATAAATCCTGGTTGCTGTC TCTTTATGAGGAGTTGTGGCCCGTTGTCCGTCAACGTGGC GTGGTGTGCTCTGTGTTTGCTGACGCAACCCCCACTGGCT GGGGCATTGCCACCACCTGTCAACTCCTTTCTGGGACTTT CGCTTTCCCCCTCCCGATCGCCACGGCAGAACTCATCGCC GCCTGCCTTGCCCGCTGCTGGACAGGGGCTAGGTTGCTGG GCACTGATAATTCCGTGGTGTTGTCGGGGAAGGGCC

[0171] In some embodiments, the vector comprises a polyadenylation (polyA) signal selected from Table 6. In some embodiments, the polyA signal comprises a polynucleotide sequence at least 75%, 80%, 85%, 90%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to any one of SEQ ID NOS 71-75.

TABLE-US-00006 TABLE 6 POLY- SEQ ADENYLATION ID SITE SEQUENCE NO: Rabbit globin TGGCTAATAAAGGAAATTTATTTTCATTGCAATAGTGTG 71 (pAGlobin-Oc) TTGGAATTTTTTGTGTCTCTCACTCGGAAGAACATATGG GAGGGCAAATCATTTAAAACATCAGAATGAGTATTTGGT TTAGAGTTTGGCAACATATGCCCATATGCTGGCTGCCAT GAACAAAGGTTGGCTATAAAGAGGTCATCAGTATATGAA ACAGCCCCCTGCTGTCCATTCCTTATTCCATAGAAAAGC CTTGACTTGAGGTTAGATTTTTTTTATATTTTGTTTTGT GTTATTTTTTTCTTTAACATCCCTAAAATTTTCCTTACA TGTTTTACTAGCCAGATTTTTCCTCCTCTCCTGACTACT CCCAGTCATAGCTGTCCCTCTTCTCTTATGGAGATC Bovine growth TTGCCAGCCATCTGTTGTTTGCCCCTCCCCCGTGCCTTC 72 hormone (pAGH-Bt - CTTGACCCTGGAAGGTGCCACTCCCACTGTCCTTTCCTA version 1) ATAAAATGAGGAAATTGCATCGCATTGTCTGAGTAGGTG TCATTCTATTCTGGGGGGTGGGGTGGGGCAGGACAGCAA GGGGGAGGATTGGGAATACAATAGCAGGCATGCTGGGGA TGCGGTGGGCTCTATGGGTACCCAGGTGCTGAAGAATTG ACCCGGTTCCTCCTGGG Bovine growth TTGCCAGCCATCTGTTGTTTGCCCCTCCCCCGTGCCTTC 73 hormone (pAGH-Bt - CTTGACCCTGGAAGGTGCCACTCCCACTGTCCTTTCCTA version 2) ATAAAATGAGGAAATTGCATCGCATTGTCTGAGTAGGTG TCATTCTATTCTGGGGGGTGGGGTGGGGCAGGACAGCAA GGGGGAGGATTGGGAAGACAATAGCAGGCATGCTGGGGA TGCGGTGGGCTCTATGGGTACCCAGGTGCTGAAGAATTG ACCCGGTTCCTCCTGGG Bovine growth CTGTGCCTTCTAGTTGCCAGCCATCTGTTGTTTGCCCCT 74 hormone (pAGH-Bt - CCCCCGTGCCTTCCTTGACCCTGGAAGGTGCCACTCCCA version 3) CTGTCCTTTCCTAATAAAATGAGGAAATTGCATCGCATT GTCTGAGTAGGTGTCATTCTATTCTGGGGGGTGGGGTGG GGCAGGACAGCAAGGGGGAGGATTGGGAAGACAATAGCA GGCATGCTGGGGATGCGGTGGGCTCTATGG Human growth CTGCCCGGGTGGCATCCCTGTGACCCCTCCCCAGTGCCT 75 hormone (pAGH-Hs) CTCCTGGCCCTGGAAGTTGCCACTCCAGTGCCCACCAGC CTTGTCCTAATAAAATTAAGTTGCATCATTTTGTCTGAC TAGGTGTCCTTCTATAATATTATGGGGTGGAGGGGGGTG GTATGGAGCAAGGGGCCCAAGTTGGGAAGAAACCTGTAG GGCCTGC

[0172] Illustrative vector genomes are depicted in FIGS. 1-4 and 11-14; and provided as SEQ ID NOs: 12-15 and 89-92. The expression cassette of each sequence is SEQ ID NOs: 8-11 or 93-96. In some embodiments, the vector genome comprises, consists essentially of, or consists of a polynucleotide sequence that shares at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to any one of SEQ ID NOs: 12-15 and 89-92, optionally with or without the ITR sequences. In some embodiments, the vector genome comprises, consists essentially of, or consists of a polynucleotide sequence that shares at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to any one of SEQ ID NOs: 8-11 and 93-96.

[0173] In a certain embodiment, the vector genome comprises, in 5' to 3' order, a 5' ITR; an MHCK7 promoter; a PKPa transgene; an WPRE(x) element; an pAGH-HS sequence; and a 3' ITR. The vector genome may comprise, in 5' to 3' order, the polynucleotide sequences SEQ ID NO: 31; any one of SEQ ID NOs: 3, 6, and 87; SEQ ID NO: 63; and SEQ ID NO: 75; or polynucleotide sequences sharing 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to each of the foregoing. In certain embodiments, this vector genome is packaged in an AAV9 or AAVrh74 vector. The PKP2a transgene of this embodiment is a full length transgene, i.e. a transgene encoding a PKP of at least 800 or at least 830 amino acids.

[0174] In a certain embodiment, the vector genome comprises, in 5' to 3' order, a 5' ITR; a hTnnT2 promoter; a PKPa transgene; an WPRE(x) element; an pAGH-HS sequence; and a 3' ITR. The vector genome may comprise, in 5' to 3' order, the polynucleotide sequences SEQ ID NO: 32 or 33; any one of SEQ ID NOs: 3, 6, and 87; SEQ ID NO: 63; and SEQ ID NO: 75; or polynucleotide sequences sharing 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to each of the foregoing. In certain embodiments, this vector genome is packaged in an AAV9 or AAVrh74 vector. The PKP2a transgene of this embodiment is a full length transgene, i.e. a transgene encoding a PKP of at least 800 or at least 830 amino acids.

[0175] In a certain embodiment, the vector genome comprises, in 5' to 3' order, a 5' ITR; an MHCK7 promoter; a PKPb transgene; an WPRE(x) element; an pAGH-HS sequence; and a 3' ITR. The vector genome may comprise, in 5' to 3' order, the polynucleotide sequences SEQ ID NO: 31; any one of SEQ ID NOs: 4, 7, and 88; SEQ ID NO: 63; and SEQ ID NO: 75; or polynucleotide sequences sharing 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to each of the foregoing. In certain embodiments, this vector genome is packaged in an AAV9 or AAVrh74 vector. The PKP2b transgene of this embodiment is a full length transgene, i.e. a transgene encoding a PKP of at least 800 or at least 830 amino acids.

[0176] In a certain embodiment, the vector genome comprises, in 5' to 3' order, a 5' ITR; a hTnnT2 promoter; a PKPb transgene; an WPRE(x) element; an pAGH-HS sequence; and a 3' ITR. The vector genome may comprise, in 5' to 3' order, the polynucleotide sequences SEQ ID NO: 32 or 33; any one of SEQ ID NOs: 4, 7, and 88; SEQ ID NO: 63; and SEQ ID NO: 75; or polynucleotide sequences sharing 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to each of the foregoing. In certain embodiments, this vector genome is packaged in an AAV9 or AAVrh74 vector. The PKP2b transgene of this embodiment is a full length transgene, i.e. a transgene encoding a PKP of at least 800 or at least 830 amino acids.

[0177] In a certain embodiment, the vector genome comprises, in 5' to 3' order, a 5' ITR; an MHCK7 promoter; a PKPa transgene; optionally a WPRE element; a polyadenylation sequence; and a 3' ITR. The vector genome may comprise, in 5' to 3' order, the polynucleotide sequences SEQ ID NO: 31; any one of SEQ ID NOs: 3, 6, and 87; or polynucleotide sequences sharing 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to each of the foregoing. In certain embodiments, this vector genome is packaged in an AAV9 or AAVrh74 vector. The PKP2a transgene of this embodiment is a full length transgene, i.e. a transgene encoding a PKP of at least 800 or at least 830 amino acids.

[0178] In a certain embodiment, the vector genome comprises, in 5' to 3' order, a 5' ITR; a hTnnT2 promoter; a PKPa transgene; optionally a WPRE element; a polyadenylation sequence; and a 3' ITR. The vector genome may comprise, in 5' to 3' order, the polynucleotide sequences SEQ ID NO: 32 or 33; any one of SEQ ID NOs: 3, 6, and 87; or polynucleotide sequences sharing 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to each of the foregoing. In certain embodiments, this vector genome is packaged in an AAV9 or AAVrh74 vector. The PKP2a transgene of this embodiment is a full length transgene, i.e. a transgene encoding a PKP of at least 800 or at least 830 amino acids.

[0179] In a certain embodiment, the vector genome comprises, in 5' to 3' order, a 5' ITR; an MHCK7 promoter; a PKPb transgene; optionally a WPRE element; a polyadenylation sequence; and a 3' ITR. The vector genome may comprise, in 5' to 3' order, the polynucleotide sequences SEQ ID NO: 31; any one of SEQ ID NOs: 4, 7, and 88; or polynucleotide sequences sharing 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to each of the foregoing. In certain embodiments, this vector genome is packaged in an AAV9 or AAVrh74 vector. The PKP2b transgene of this embodiment is a full length transgene, i.e. a transgene encoding a PKP of at least 800 or at least 830 amino acids.

[0180] In a certain embodiment, the vector genome comprises, in 5' to 3' order, a 5' ITR; a hTnnT2 promoter; a PKPb transgene; optionally a WPRE element; a polyadenylation sequence; and a 3' ITR. The vector genome may comprise, in 5' to 3' order, the polynucleotide sequences SEQ ID NO: 32 or 33; any one of SEQ ID NOs: 4, 7, and 88; or polynucleotide sequences sharing 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to each of the foregoing. In certain embodiments, this vector genome is packaged in an AAV9 or AAVrh74 vector. The PKP2b transgene of this embodiment is a full length transgene, i.e. a transgene encoding a PKP of at least 800 or at least 830 amino acids.

[0181] In a certain embodiment, the vector genome comprises, in 5' to 3' order, a 5' ITR; an MHCK7 promoter; SV40 intron; a PKPa transgene; optionally a WPRE element; a polyadenylation sequence; and a 3' ITR. The vector genome may comprise, in 5' to 3' order, the polynucleotide sequences SEQ ID NO: 31; SEQ ID NO: 53 or 61; any one of SEQ ID NOs: 3, 6, and 87; or polynucleotide sequences sharing 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to each of the foregoing. In certain embodiments, this vector genome is packaged in an AAV9 or AAVrh74 vector. The PKP2a transgene of this embodiment is a full length transgene, i.e. a transgene encoding a PKP of at least 800 or at least 830 amino acids.

[0182] In a certain embodiment, the vector genome comprises, in 5' to 3' order, a 5' ITR; a hTnnT2 promoter; SV40 intron; a PKPa transgene; optionally a WPRE element; a polyadenylation sequence; and a 3' ITR. The vector genome may comprise, in 5' to 3' order, the polynucleotide sequences SEQ ID NO: 32 or 33; SEQ ID NO: 53 or 61; any one of SEQ ID NOs: 3, 6, and 87; or polynucleotide sequences sharing 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to each of the foregoing. In certain embodiments, this vector genome is packaged in an AAV9 or AAVrh74 vector. The PKP2a transgene of this embodiment is a full length transgene, i.e. a transgene encoding a PKP of at least 800 or at least 830 amino acids.

[0183] In a certain embodiment, the vector genome comprises, in 5' to 3' order, a 5' ITR; an MHCK7 promoter; SV40 intron; a PKPb transgene; optionally a WPRE element; a polyadenylation sequence; and a 3' ITR. The vector genome may comprise, in 5' to 3' order, the polynucleotide sequences SEQ ID NO: 31; SEQ ID NO: 53 or 61; any one of SEQ ID NOs: 4, 7, and 88; or polynucleotide sequences sharing 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to each of the foregoing. In certain embodiments, this vector genome is packaged in an AAV9 or AAVrh74 vector. The PKP2b transgene of this embodiment is a full length transgene, i.e. a transgene encoding a PKP of at least 800 or at least 830 amino acids.

[0184] In a certain embodiment, the vector genome comprises, in 5' to 3' order, a 5' ITR; a hTnnT2 promoter; SV40 intron; a PKPb transgene; optionally a WPRE element; a polyadenylation sequence; and a 3' ITR. The vector genome may comprise, in 5' to 3' order, the polynucleotide sequences SEQ ID NO: 32 or 33; SEQ ID NO: 53 or 61; any one of SEQ ID NOs: 4, 7, and 88; or polynucleotide sequences sharing 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity to each of the foregoing. In certain embodiments, this vector genome is packaged in an AAV9 or AAVrh74 vector. The PKP2b transgene of this embodiment is a full length transgene, i.e. a transgene encoding a PKP of at least 800 or at least 830 amino acids.

[0185] In each case the optionally WPRE element may be present or absent.

Adeno-Associated Virus Vector

[0186] AAV vectors useful in the practice of the present invention can be packaged into AAV virions (viral particles) using various systems including adenovirus-based and helper-free systems. Standard methods in AAV biology include those described in Kwon and Schaffer. Pharm Res. (2008) 25(3):489-99; Wu et al. Mol. Ther. (2006) 14(3):316-27. Burger et al. Mol. Ther. (2004) 10(2):302-17; Grimm et al. Curr Gene Ther. (2003) 3(4):281-304; Deyle D R, Russell D W. Curr Opin Mol Ther. (2009) 11(4):442-447; McCarty et al. Gene Ther. (2001) 8(16):1248-54; and Duan et al. Mol Ther. (2001) 4(4):383-91. Helper-free systems included those described in U.S. Pat. Nos. 6,004,797; 7,588,772; and 7,094,604;

[0187] AAV DNA in the rAAV genomes may be from any AAV variant or serotype for which a recombinant virus can be derived including, but not limited to, AAV variants or serotypes AAV-1, AAV-2, AAV-3, AAV-4, AAV-5, AAV-6, AAV-7, AAV-8, AAV-9, AAV-10, AAV-11, AAV-12, AAV-13 and AAVrh10. Production of pseudotyped rAAV is disclosed in, for example, WO 01/83692. Other types of rAAV variants, for example rAAV with capsid mutations, are also contemplated. See, for example, Marsic et al., Molecular Therapy, 22(11): 1900-1909 (2014). The nucleotide sequences of the genomes of various AAV serotypes are known in the art.

[0188] In some cases, the rAAV comprises a self-complementary genome. As defined herein, an rAAV comprising a "self-complementary" or "double stranded" genome refers to an rAAV which has been engineered such that the coding region of the rAAV is configured to form an intra-molecular double-stranded DNA template, as described in McCarty et al. Self-complementary recombinant adeno-associated virus (scAAV) vectors promoter efficient transduction independently of DNA synthesis. Gene Therapy. 8 (16): 1248-54 (2001). The present disclosure contemplates the use, in some cases, of an rAAV comprising a self-complementary genome because upon infection (such transduction), rather than waiting for cell mediated synthesis of the second strand of the rAAV genome, the two complementary halves of scAAV will associate to form one double stranded DNA (dsDNA) unit that is ready for immediate replication and transcription. It will be understood that instead of the full coding capacity found in rAAV (4.7-6 kb), rAAV comprising a self-complementary genome can only hold about half of that amount (.apprxeq.2.4 kb).

[0189] In other cases, the rAAV vector comprises a single stranded genome. As defined herein, a "single standard" genome refers to a genome that is not self-complementary. In most cases, non-recombinant AAVs have singled stranded DNA genomes. There have been some indications that rAAVs should be scAAVs to achieve efficient transduction of cells. The present disclosure contemplates, however, rAAV vectors that maybe have singled stranded genomes, rather than self-complementary genomes, with the understanding that other genetic modifications of the rAAV vector may be beneficial to obtain optimal gene transcription in target cells. In some cases, the present disclosure relates to single-stranded rAAV vectors capable of achieving efficient gene transfer to anterior segment in the mouse eye. See Wang et al. Single stranded adeno-associated virus achieves efficient gene transfer to anterior segment in the mouse eye. PLoS ONE 12(8): e0182473 (2017).

[0190] In some cases, the rAAV vector is of the serotype AAV1, AAV2, AAV4, AAV5, AAV6, AAV7, AAV8, AAV9, AAV10, AAV11, AAV12, AAV13, AAVrh10, or AAVrh74. Production of pseudotyped rAAV is disclosed in, for example, WO 01/83692. Other types of rAAV variants, for example rAAV with capsid mutations, are also contemplated. See, for example, Marsic et al., Molecular Therapy, 22(11): 1900-1909 (2014). In some cases, the rAAV vector is of the serotype AAV9. In some embodiments, said rAAV vector is of serotype AAV9 and comprises a single stranded genome. In some embodiments, said rAAV vector is of serotype AAV9 and comprises a self-complementary genome. In some embodiments, a rAAV vector comprises the inverted terminal repeat (ITR) sequences of AAV2. In some embodiments, the rAAV vector comprises an AAV2 genome, such that the rAAV vector is an AAV-2/9 vector, an AAV-2/6 vector, or an AAV-2/8 vector.

[0191] Full-length sequences and sequences for capsid genes for most known AAVs are provided in U.S. Pat. No. 8,524,446, which is incorporated herein in its entirety.

[0192] AAV vectors may comprise wild-type AAV sequence or they may comprise one or more modifications to a wild-type AAV sequence. In certain embodiments, an AAV vector comprises one or more amino acid modifications, optionally substitutions, deletions, or insertions, within a capsid protein, optionally VP1, VP2 and/or VP3. In particular embodiments, the modification provides for reduced immunogenicity when the AAV vector is provided to a subject.

[0193] Capsid proteins of a rAAV may be modified so that the rAAV is targeted to a particular target tissue of interest such as endothelial cells or more particularly endothelial tip cells. In some embodiments, the rAAV is directly injected into the intracerebroventricular space of the subject.

[0194] In some embodiments, the rAAV virion is an AAV2 rAAV virion. The capsid many be an AAV2 capsid or functional variant thereof. In some embodiments, the AAV2 capsid shares at least 98%, 99%, or 100% identity to a reference AAV2 capsid, e.g., SEQ ID NO: 76.

[0195] In some embodiments, the rAAV virion is an AAV9 rAAV virion. The capsid many be an AAV9 capsid or functional variant thereof. In some embodiments, the AAV9 capsid shares at least 98%, 99%, or 100% identity to a reference AAV9 capsid, e.g., SEQ ID NO: 77.

[0196] In some embodiments, the rAAV virion is an AAV6 rAAV virion. The capsid many be an AAV9 capsid or functional variant thereof. In some embodiments, the AAV6 capsid shares at least 98%, 99%, or 100% identity to a reference AAV6 capsid, e.g., SEQ ID NO: 78.

[0197] In some embodiments, the rAAV virion is an AAVrh.10 rAAV virion. The capsid many be an AAV9 capsid or functional variant thereof. In some embodiments, the AAVrh.10 capsid shares at least 98%, 99%, or 100% identity to a reference AAVrh.10 capsid, e.g., SEQ ID NO: 79.

[0198] In some embodiments, the capsid protein is encoded by a polynucleotide supplied on a plasmid in trans to the transfer plasmid. The polynucleotide sequence of wild-type AAVrh74 cap is provided as SEQ ID NO: 80.

[0199] The disclosure further provides protein sequences for AAVrh74 VP1, VP2, and VP3, including SEQ ID NOs: 81-83, and homologs or functional variants thereof.

[0200] In certain cases, the AAVrh74 capsid comprises the amino acid sequence set forth in SEQ ID NO: 81. In some embodiments, the rAAV vector comprises a polypeptide that comprises, or consists essentially of, or yet further consists of a sequence, e.g., at least 65%, at least 70%, at least 75%, at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, or 89%, more typically 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to amino acid sequence of AAVrh74 VP1 which is set forth in SEQ ID NO: 81. In some embodiments, the rAAV vector comprises a polypeptide that comprises, or consists essentially of, or yet further consists of a sequence, e.g., at least 65%, at least 70%, at least 75%, at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, or 89%, more typically 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to amino acid sequence of AAVrh74 VP2 which is set forth in SEQ ID NO: 82. In some embodiments, the rAAV vector comprises a polypeptide that comprises, or consists essentially of, or yet further consists of a sequence, e.g., at least 65%, at least 70%, at least 75%, at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, or 89%, more typically 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more identical to amino acid sequence of AAVrh74 VP3 which is set forth in SEQ ID NO: 83.

[0201] In some embodiments, the rAAV virion is an AAV-PHP.B rAAV virion or a neutrotrophic variant thereof, such as, without limitation, those disclosed in Int'l Pat. Pub. Nos. WO 2015/038958 A1 and WO 2017/100671 A1. For example, the AAV capsid may comprise at least 4 contiguous amino acids from the sequence TLAVPFK (SEQ ID NO:85) or KFPVALT (SEQ ID NO:86), e.g., inserted between a sequence encoding for amino acids 588 and 589 of AAV9.

[0202] The capsid many be an AAV-PHP.B capsid or functional variant thereof. In some embodiments, the AAV-PHP.B capsid shares at least 98%, 99%, or 100% identity to a reference AAV-PHP.B capsid, e.g., SEQ ID NO: 84.

[0203] Further AAV capsids used in the rAAV virions of the disclosure include those disclosed in Pat. Pub. Nos. WO 2009/012176 A2 and WO 2015/168666 A2.

[0204] Without being bound by theory, the present inventors have determined that an AAV9 vector, AAVrh.74, or an AAVrh.10 vector will confer desirable cardiac tropism on the vector. Without being bound by theory, the present inventors have further determined that an AAV9 vector, AAVrh.74, or an AAVrh.10 vector may provide desired specificity to cardiac cells.

[0205] In an aspect, the disclosure provides pharmaceutical compositions comprising the rAAV virion of the disclosure and one or more pharmaceutically acceptable carriers, diluents, or excipients.

[0206] For purposes of administration, optionally by injection, various solutions can be employed, such as sterile aqueous solutions. Such aqueous solutions can be buffered, if desired, and the liquid diluent first rendered isotonic with saline or glucose. Solutions of rAAV as a free acid (DNA contains acidic phosphate groups) or a pharmacologically acceptable salt can be prepared in water suitably mixed with a surfactant such as Poloxamer 188, e.g., at 0.001% or 0.01%. A dispersion of rAAV can also be prepared in glycerol, liquid polyethylene glycols and mixtures thereof and in oils. Under ordinary conditions of storage and use, these preparations contain a preservative to prevent the growth of microorganisms. In this connection, the sterile aqueous media employed are all readily obtainable by standard techniques well-known to those skilled in the art.

[0207] The pharmaceutical forms suitable for injectable use include but are not limited to sterile aqueous solutions or dispersions and sterile powders for the extemporaneous preparation of sterile injectable solutions or dispersions. In all cases the form is sterile and must be fluid to the extent that easy syringability exists. It must be stable under the conditions of manufacture and storage and must be preserved against the contaminating actions of microorganisms such as bacteria and fungi. The carrier can be a solvent or dispersion medium containing, for example, water, ethanol, polyol (for example, glycerol, propylene glycol, liquid polyethylene glycol and the like), suitable mixtures thereof, and vegetable oils. The proper fluidity can be maintained, for example, by the use of a coating such as lecithin, by the maintenance of the required particle size in the case of a dispersion and by the use of surfactants. The prevention of the action of microorganisms can be brought about by various antibacterial and antifungal agents, for example, parabens, chlorobutanol, phenol, sorbic acid, thimerosal and the like. In many cases it will be preferable to include isotonic agents, for example, sugars or sodium chloride. Prolonged absorption of the injectable compositions can be brought about by use of agents delaying absorption, for example, aluminum monostearate and gelatin.

[0208] Sterile injectable solutions may be prepared by incorporating rAAV in the required amount in the appropriate solvent with various other ingredients enumerated above, as required, followed by filter sterilization. Generally, dispersions are prepared by incorporating the sterilized active ingredient into a sterile vehicle which contains the basic dispersion medium and the required other ingredients from those enumerated above. In the case of sterile powders for the preparation of sterile injectable solutions, the certain methods of preparation are vacuum drying and the freeze-drying technique that yield a powder of the active ingredient plus any additional desired ingredient from the previously sterile-filtered solution thereof.

[0209] In another aspect, the disclosure comprises a kit comprising an rAAV virion of the disclosure and instructions for use.

[0210] In an aspect, the disclosure provides a method of increasing PKP2 activity in a cell, comprising contacting the cell with an rAAV of the disclosure. In another aspect, the disclosure provides a method of increasing PKP2 activity in a subject, comprising administering to the subject an rAAV of the disclosure. In some embodiments, the cell and/or subject is deficient in PKP2 messenger RNA or PKP2 protein expression levels and/or activity and/or comprises a loss-of-function mutation in PKP2. The cell may be a cardiac cell, e.g. a cardiomyocyte cell. In particular embodiments, the subject is a mammal, e.g., a human.

[0211] In some embodiments, the method promotes survival of cardiac cell, e.g. a cardiomyocyte cell, in cell culture and/or in vivo. In some embodiments, the method promotes and/or restores function of the heart.

[0212] In another aspect, the disclosure provides a method of treating a disease or disorder in a subject in need thereof, comprising administering to the subject an effective amount of an rAAV virion of the disclosure. In some embodiments, the disease or disorder is a cardiac disease or disorder. Illustrative cardiac disorders include heart failure, arrhythmogenic right ventricular cardiomyopathy (ARVC), Brugada syndrome (BrS) and idiopathic ventricular fibrillation. In certain embodiments, the subject suffers from or is at risk for arrhythmogenic right ventricular cardiomyopathy (ARVC). In particular embodiments, the subject is a mammal, e.g., a human, having a loss-of-function mutation in a PKP2 gene. In particular methods, treatment with the rAAV virion results in expression of the PKP2 protein encoded by the rAAV virion in the subject, e.g., in the subject's heart or cardiac tissue. In certain embodiments, treatment with the rAAV virion results in at least two-fold, at least five-fold, at least ten-fold, or more PKP2 protein levels detectable in the subject's heart.

[0213] The AAV-mediated delivery of PKP2 protein to the heart may increase life span, prevent or attenuate cardiac cell degeneration, heart failure, scarring, reduced ejection fraction, arrythmia, angina, exercise intolerance, angina (chest pain), sudden cardiac death, exertional myalgias and cramps. The AAV-mediated delivery of PKP2 protein to the heart may show improvement from, or prevent normal disease course detected by use of pathological electrocardiogram, cardiac MRI, heart biopsy, decrease in paroxysmal ventricular arrhythmias, decrease in sudden cardiac death, and/or decrease in or lack of further development of fibro-fatty deposits in right ventricular myocardium. The methods of the disclosure may prevent a decrease in, restore, and/or increase right ventricular ejection fraction (RVEF).

[0214] The methods disclosed herein may provide efficient biodistribution in the heart. They may result in sustained in expression in all, or a substantial fraction of, cardiac cells, e.g., cardiomyocytes. Notably, the methods disclosed herein may provide long-lasting expression of PKP2 protein throughout the life of the subject following AAV vector administration. In some embodiments, PKP2 protein expression in response to treatment lasts at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, or 40 years.

[0215] Combination therapies are also contemplated by the invention. Combinations of methods of the invention with standard medical treatments (e.g., corticosteroids or topical pressure reducing medications) are specifically contemplated, as are combinations with novel therapies. In some cases, a subject may be treated with a steroid and/or combination of immune suppressing agents to prevent or to reduce an immune response to administration of a rAAV described herein.

[0216] In some embodiments, the AAV vector is administered at a dose of between about 1.times.10.sup.12 and 5.times.10.sup.14 vector genomes (vg) or between about 1.times.10.sup.12 and 6.times.10.sup.14 vg of the AAV vector per kilogram (vg) of total body mass of the subject (vg/kg). In some embodiments, the AAV vector is administered at a dose of between about 1.times.10.sup.13 and 5.times.10.sup.14 vg/kg. In some embodiments, the AAV vector is administered at a dose of between about 5.times.10.sup.13 and 3.times.10.sup.14 vg/kg. In some embodiments, the AAV vector is administered at a dose of between about 5.times.10.sup.13 and 1.times.10.sup.14 vg/kg. In some embodiments, the AAV vector is administered at a dose of less than about 1.times.10.sup.12 vg/kg, less than about 3.times.10.sup.12 vg/kg, less than about 5.times.10.sup.12 vg/kg, less than about 7.times.10.sup.12 vg/kg, less than about 1.times.10.sup.13 vg/kg, less than about 3.times.10.sup.13 vg/kg, less than about 5.times.10.sup.13 vg/kg, less than about 7.times.10.sup.13 vg/kg, less than about 1.times.10.sup.13 vg/kg, less than about 3.times.10.sup.14 vg/kg, less than about 5.times.10.sup.14 vg/kg, less than about 7.times.10.sup.14 vg/kg, less than about 1.times.10.sup.15 vg/kg, less than about 3.times.10.sup.15 vg/kg, less than about 5.times.10.sup.15 vg/kg, or less than about 7.times.10.sup.15 vg/kg. In certain embodiments, the AAV vector delivered at any of these doses is an AAV9 vector or an AAV rh74 vector. In some cases, it may be advantageous to use a higher dose for an AAV rh74 vector than for an AAV9 vector.

[0217] In some embodiments, the AAV vector is administered at a dose of about 1.times.10.sup.12 vg/kg, about 3.times.10.sup.12 vg/kg, about 5.times.10.sup.12 vg/kg, about 7.times.10.sup.12 vg/kg, about 1.times.10.sup.13 vg/kg, about 3.times.10.sup.13 vg/kg, about 5.times.10.sup.13 vg/kg, about 7.times.10.sup.13 vg/kg, about 1.times.10.sup.14 vg/kg, about 3.times.10.sup.14 vg/kg, about 5.times.10.sup.14 vg/kg, about 7.times.10.sup.14 vg/kg, about 1.times.10.sup.15 vg/kg, about 3.times.10.sup.15 vg/kg, about 5.times.10.sup.15 vg/kg, or about 7.times.10.sup.15 vg/kg. In certain embodiments, the AAV vector delivered at any of these doses is an AAV9 vector or an AAV rh74 vector.

[0218] In some embodiments, the AAV vector is administered at a dose of 1.times.10.sup.12 vg/kg, 3.times.10.sup.12 vg/kg, 5.times.10.sup.12 vg/kg, 7.times.10.sup.12 vg/kg, 1.times.10.sup.13 vg/kg, 3.times.10.sup.13 vg/kg, 5.times.10.sup.13 vg/kg, 7.times.10.sup.13 vg/kg, 1.times.10.sup.14 vg/kg, 3.times.10.sup.14 vg/kg, 5.times.10.sup.14 vg/kg, 7.times.10.sup.14 vg/kg, 1.times.10.sup.15 vg/kg, 3.times.10.sup.15 vg/kg, 5.times.10.sup.15 vg/kg, or 7.times.10.sup.15 vg/kg. In certain embodiments, the AAV vector delivered at any of these doses is an AAV9 vector or an AAV rh74 vector.

[0219] In some embodiments, the AAV vector is administered systemically at a dose of between about 1.times.10.sup.12 and 5.times.10.sup.14 vector genomes (vg) of the AAV vector per kilogram (vg) of total body mass of the subject (vg/kg). In some embodiments, the AAV vector is administered systemically at a dose of between about 1.times.10.sup.13 and 5.times.10.sup.14 vg/kg. In some embodiments, the AAV vector is administered systemically at a dose of between about 5.times.10.sup.13 and 3.times.10.sup.14 vg/kg. In some embodiments, the AAV vector is administered systemically at a dose of between about 5.times.10.sup.13 and 1.times.10.sup.14 vg/kg. In some embodiments, the AAV vector is administered systemically at a dose of less than about 1.times.10.sup.12 vg/kg, less than about 3.times.10.sup.12 vg/kg, less than about 5.times.10.sup.12 vg/kg, less than about 7.times.10.sup.12 vg/kg, less than about 1.times.10.sup.13 vg/kg, less than about 3.times.10.sup.13 vg/kg, less than about 5.times.10.sup.13 vg/kg, less than about 7.times.10.sup.13 vg/kg, less than about 1.times.10.sup.14 vg/kg, less than about 3.times.10.sup.14 vg/kg, less than about 5.times.10.sup.14 vg/kg, less than about 7.times.10.sup.14 vg/kg, less than about 1.times.10.sup.15 vg/kg, less than about 3.times.10.sup.15 vg/kg, less than about 5.times.10.sup.15 vg/kg, or less than about 7.times.10.sup.15 vg/kg. In certain embodiments, the AAV vector delivered at any of these doses is an AAV9 vector or an AAV rh74 vector.

[0220] In some embodiments, the AAV vector is administered systemically at a dose of about 1.times.10.sup.12 vg/kg, about 3.times.10.sup.12 vg/kg, about 5.times.10.sup.12 vg/kg, about 7.times.10.sup.12 vg/kg, about 1.times.10.sup.13 vg/kg, about 3.times.10.sup.13 vg/kg, about 5.times.10.sup.13 vg/kg, about 7.times.10.sup.13 vg/kg, about 1.times.10.sup.14 vg/kg, about 3.times.10.sup.14 vg/kg, about 5.times.10.sup.14 vg/kg, about 7.times.10.sup.14 vg/kg, about 1.times.10.sup.15 vg/kg, about 3.times.10.sup.15 vg/kg, about 5.times.10.sup.15 vg/kg, or about 7.times.10.sup.15 vg/kg. In certain embodiments, the AAV vector delivered at any of these doses is an AAV9 vector or an AAV rh74 vector.

[0221] In some embodiments, the AAV vector is administered systemically at a dose of 1.times.10.sup.12 vg/kg, 3.times.10.sup.12 vg/kg, 5.times.10.sup.12 vg/kg, 7.times.10.sup.12 vg/kg, 1.times.10.sup.13 vg/kg, 3.times.10.sup.13 vg/kg, 5.times.10.sup.13 vg/kg, 7.times.10.sup.13 vg/kg, 1.times.10.sup.14 vg/kg, 3.times.10.sup.14 vg/kg, 5.times.10.sup.14 vg/kg, 7.times.10.sup.14 vg/kg, 1.times.10.sup.15 vg/kg, 3.times.10.sup.15 vg/kg, 5.times.10.sup.15 vg/kg, or 7.times.10.sup.15 vg/kg. In certain embodiments, the AAV vector delivered at any of these doses is an AAV9 vector or an AAV rh74 vector.

[0222] In some embodiments, the AAV vector is administered intravenously at a dose of between about 1.times.10.sup.12 and 5.times.10.sup.14 vector genomes (vg) of the AAV vector per kilogram (vg) of total body mass of the subject (vg/kg). In some embodiments, the AAV vector is administered intravenously at a dose of between about 1.times.10.sup.13 and 5.times.10.sup.14 vg/kg. In some embodiments, the AAV vector is administered intravenously at a dose of between about 5.times.10.sup.13 and 3.times.10.sup.14 vg/kg. In some embodiments, the AAV vector is administered intravenously at a dose of between about 5.times.10.sup.13 and 1.times.10.sup.14 vg/kg. In some embodiments, the AAV vector is administered intravenously at a dose of less than about 1.times.10.sup.12 vg/kg, less than about 3.times.10.sup.12 vg/kg, less than about 5.times.10.sup.12 vg/kg, less than about 7.times.10.sup.12 vg/kg, less than about 1.times.10.sup.13 vg/kg, less than about 3.times.10.sup.13 vg/kg, less than about 5.times.10.sup.13 vg/kg, less than about 7.times.10.sup.13 vg/kg, less than about 1.times.10.sup.14 vg/kg, less than about 3.times.10.sup.14 vg/kg, less than about 5.times.10.sup.14 vg/kg, less than about 7.times.10.sup.14 vg/kg, less than about 1.times.10.sup.15 vg/kg, less than about 3.times.10.sup.15 vg/kg, less than about 5.times.10.sup.15 vg/kg, or less than about 7.times.10.sup.15 vg/kg. In certain embodiments, the AAV vector delivered at any of these doses is an AAV9 vector or an AAV rh74 vector.

[0223] In some embodiments, the AAV vector is administered intravenously at a dose of about 1.times.10.sup.12 vg/kg, about 3.times.10.sup.12 vg/kg, about 5.times.10.sup.12 vg/kg, about 7.times.10.sup.12 vg/kg, about 1.times.10.sup.13 vg/kg, about 3.times.10.sup.13 vg/kg, about 5.times.10.sup.13 vg/kg, about 7.times.10.sup.13 vg/kg, about 1.times.10.sup.14 vg/kg, about 3.times.10.sup.14 vg/kg, about 5.times.10.sup.14 vg/kg, about 7.times.10.sup.14 vg/kg, about 1.times.10.sup.15 vg/kg, about 3.times.10.sup.15 vg/kg, about 5.times.10.sup.15 vg/kg, or about 7.times.10.sup.15 vg/kg.

[0224] In some embodiments, the AAV vector is administered intravenously at a dose of 1.times.10.sup.12 vg/kg, 3.times.10.sup.12 vg/kg, 5.times.10.sup.12 vg/kg, 7.times.10.sup.12 vg/kg, 1.times.10.sup.13 vg/kg, 3.times.10.sup.13 vg/kg, 5.times.10.sup.13 vg/kg, 7.times.10.sup.13 vg/kg, 1.times.10.sup.14 vg/kg, 3.times.10.sup.14 vg/kg, 5.times.10.sup.14 vg/kg, 7.times.10.sup.14 vg/kg, 1.times.10.sup.15 vg/kg, 3.times.10.sup.15 vg/kg, 5.times.10.sup.15 vg/kg, or 7.times.10.sup.15 vg/kg. In certain embodiments, the AAV vector delivered at any of these doses is an AAV9 vector or an AAV rh74 vector.

[0225] Evidence of functional improvement, clinical benefit or efficacy in patients may be revealed by change in New York Heart Association functional classification (NYHA Class), pathological electrocardiogram, cardiac MRI, heart biopsy, decrease in paroxysmal ventricular arrhythmias, decrease in sudden cardiac death, and/or decrease in or lack of further development of fibro-fatty deposits in right ventricular myocardium. Benefit may be observed in electrocardiographic features normally associated with arrhythmogenic right ventricular cardiomyopathy such as T wave inversion, prolonged S-wave upstroke, localized QRS widening, and/or paroxysmal episodes of ventricular tachycardia.

[0226] In some embodiments, the method prevents or reduces a decrease in left ventricle ejection fraction percentage (LVEF %), optionally by about 50%, about 60%, about 70%, about 80%, about 90%, or about 100% compared to the decrease observed in an untreated subject suffering from or at risk for disease or disorder related to or caused by loss of function in PKP2.

[0227] In some embodiments, the method prevents or reduces a decrease in left ventricle fractional shortening percentage (FS %), optionally by about 50%, about 60%, about 70%, about 80%, about 90%, or about 100% compared to the decrease observed in an untreated subject suffering from or at risk for disease or disorder related to or caused by loss of function in PKP2.

[0228] In some embodiments, the method prevents or reduces an increase in right ventricle area in millimeters squared (RV Area (mm2), optionally by about 50%, about 60%, about 70%, about 80%, about 90%, or about 100% compared to the increase observed in an untreated subject suffering from or at risk for disease or disorder related to or caused by loss of function in PKP2.

[0229] In some embodiments, the method prevents or reduces a decrease in right ventricle velocity time integral in millimeters per second (RV VTI (mm/sec), optionally by about 50%, about 60%, about 70%, about 80%, about 90%, or about 100% compared to the decrease observed in an untreated subject suffering from or at risk for disease or disorder related to or caused by loss of function in PKP2.

[0230] In some embodiments, the method prevents or reduces an increase in left ventricle or right ventricle fibrosis, optionally by about 50%, about 60%, about 70%, about 80%, about 90%, or about 100% compared to the increase observed in an untreated subject suffering from or at risk for disease or disorder related to or caused by loss of function in PKP2.

[0231] Administration of an effective dose of the compositions may be by routes standard in the art including, but not limited to, systemic, local, direct injection, intravenous, intracardiac administration. In some cases, administration comprises systemic, local, direct injection, intravenous, intracardiac injection. Administration may be performed by cardiac catheterization.

[0232] In some embodiments, the disclosure provides for local administration and systemic administration of an effective dose of rAAV and compositions of the invention. For example, systemic administration may be administration into the circulatory system so that the entire body is affected. Systemic administration includes parental administration through injection, infusion or implantation. Routes of administration for the compositions disclosed herein include intravenous ("IV") administration, intraperitoneal ("IP") administration, intramuscular ("IM") administration, intralesional administration, or subcutaneous ("SC") administration, or the implantation of a slow-release device, e.g., a mini-osmotic pump, a depot formulation, etc. In some embodiments, the methods of the disclosure comprise administering an AAV vector of the disclosure, or pharmaceutical composition thereof by intravenous, intramuscular, intraarterial, intrarenal, intraurethral, intracardiac, intracoronary, intramyocardial, intradermal, epidural, subcutaneous, intraperitoneal, intraventricular, ionophoretic or intracranial administration.

[0233] In particular, administration of rAAV of the present invention may be accomplished by using any physical method that will transport the rAAV recombinant vector into the target tissue of an animal. Administration includes, but is not limited to, injection into the heart.

[0234] In some embodiments, the methods of the disclosure comprise intracardiac delivery. Infusion may be performed using specialized cannula, catheter, syringe/needle using an infusion pump. Administration may comprise delivery of an effective amount of the rAAV virion, or a pharmaceutical composition comprising the rAAV virion, to the heart. These may be achieved, e.g., via intravenous, intramuscular, intraarterial, intrarenal, intraurethral, intracardiac, intracoronary, intramyocardial, intradermal, epidural, subcutaneous, intraperitoneal, intraventricular, ionophoretic or intracranial administration. The compositions of the disclosure may further be administered intravenously.

[0235] The method of treatment disclosed herein may reduce and/or prevent one or more symptoms including but not limited to ventricular hypertrophy, ventricular tachycardia, exercise intolerance, angina, and reduced RVEF.

EXAMPLES

Example 1: Pre-Clinical Bioactivity and Efficacy

[0236] Vectors illustrated in FIGS. 1-4 are tested. AAV vectors or respective expression cassettes are tested in vitro using cultured cardiomyocytes (e.g., induced pluripotent stem cell cardiomyocytes, iPSC-CMs) or other cells amenable to transfection or transduction with these constructs. Expression of PKP2 is assessed by immunofluorescence and Western blot. Cell-based studies employing patient iPSC-derived cardiomyocytes will reveal benefit of overexpression of PKP2 transgene (either following AAV vector transduction and/or transfection with vector plasmids) by a decreased adipogenic potential (e.g. less lipid accumulation), decreased upregulation or abnormal peroxisome proliferator-activated receptor gamma activation, associated with increased density of PKP2.

[0237] Selected vectors are tested in vivo using mutant mouse models of cardiomyopathy (e.g., PKP2-cKO, among others). Evidence of benefit of AAV mediated overexpression of PKP2 may be revealed using a cardiomyocyte-specific, tamoxifen-activated, PKP2 knockout murine line, referred to as "PKP2-cKO". This mouse model allows control of the onset of PKP2 loss of expression, limits loss of PKP2 to adult myocytes, and initiates a progression of molecular and functional events leading to an arrhythmogenic cardiomyopathy, with right ventricular predominance in this mouse. Additional mouse models that result in similar course of pathology may also be utilized to reveal benefit of AAV-mediated overexpression of PKP2 in cardiomyocytes. Benefit of AAV-mediated PKP2 overexpression would be evidenced by increase in survival, mitigation of the normal progression of cardiomyopathy observed on echocardiograms from left and/or right ventricle (e.g. greater left ventricular ejection fraction, greater left ventricle fractional shortening, and greater right ventricle velocity time interval, compared to PKP cKO formulation buffer control animals).

[0238] Electrophysiological evidence of functional benefit of AAV-mediated delivery of PKP2 protein is demonstrated by mitigation of disease-related disrupted calcium dynamics in affected cardiomyocytes, most notably on measures of L-type calcium current, sarcoplasmic reticulum calcium leak, diastolic calcium leak, as well as standard measures of calcium transients in affected (e.g., PKP2-deficient) cardiomyocytes such as time to peak amplitude and relaxation time constants. Histological analyses will reveal benefit of AAV-mediated PKP2 overexpression by diminished appearance of disease-related collagen deposition (e.g., via trichrome stain) in various regions of the heart including ventricles, compared to cKO formulation buffer injected controls. Additional benefit will also be revealed by evaluating cardiomyocyte ventricular proteins involved in calcium signaling pathways, measured by increased (i.e., normalized) relative levels of Casq2, and/or Trdn, and/or Cav 1.2, and/or AnkB and/or RyR2, relative to non AAV-PKP2 treated, PKP2-cKO diseased controls.

Example 2: In Vitro Testing of Adeno-Associated Virus Vectors

[0239] AAV vectors are described herein (see FIGS. 11-12) were prepared and used to transduce differentiated AC16 cells, a human cardiomyocyte cell line. Expression levels of PKP2 (PKP2a isoform) were assessed by Western Blot (FIGS. 5A-5B). Surprisingly, the MHCK7 promoter causes robust expression of PKP2 in cardiomyocytes, whereas the hTnnT2 promoter ("hTnT") generates marginal PKP2 levels above background under the current testing conditions. The AAVrh.74 serotype induced higher expression of PKP2 than the AAV9 serotype vector.

[0240] Based on these results, we conclude that AAV9 vectors or AAVrh74 vectors can effectively be used to express PKP2 in cardiomyocytes, and that the MHCK7 promoter is superior to the hTnnT2 promoter when solely evaluating the relative levels of PKP2 expression.

Example 3: In Vivo Efficacy of Adeno-Associated Virus Vectors

[0241] A "PKP2-cKO" mouse model of PKP2-deficiency, as described in Cerrone et al., Nat Comm., 2017 was obtained. This cardiomyocyte-specific, tamoxifen-activated PKP2 knockout murine line (aMHC-Cre-ER(T2)/Pkp2 fl/fl; referred to as "PKP2-cKO") was utilized to control the onset of PKP2 loss of expression (see Cerrone et al., Nat Comm, 2017). The conditional loss of PKP2 expression in this mouse model is limited to adult myocytes and the temporal progression of the molecular, structural and functional events as a consequence of PKP2-cKO have been established (Cerrone et al., Nat Comm, 2017). PKP2 deficiency in adult ventricular myocytes is sufficient to cause an arrhythmogenic cardiomyopathy of RV predominance, which includes the `hallmark` functional, molecular, and structural indices consistent with the disease phenotype of ARVC.

[0242] PKP2-Cko mice were injected with tamoxifen, causing myocyte-specific knockout of PKP2. Mice were injected with AAV vectors (as described below) at 3.times.10.sup.13 vg/kg by intravenous (tail vein) injection. Four weeks later, myocyte-specific knockout of PKP2 was induced by treatment of the mice with tamoxifen. The vector genomes used were:

[0243] 5' ITR; MHCK7 promoter (with its enhancer element); SV40 intron; Kozak sequence; PKPa transgene; WPRE(x); hGH polyadenylation sequence); 3' ITR--shown in FIG. 11

[0244] 5' ITR; hTnnT2 promoter (with exon 1); Kozak sequence; PKPa transgene; WPRE(x); hGH polyadenylation sequence); 3' ITR--shown in FIG. 12.

[0245] Each vector genome was tested in a AAV9 serotype or AAVrh74 serotype vector.

[0246] At 21 or 28 days after tamoxifen treatment, which is 25 or 32 weeks after AAV treatment, mice were evaluated for various physiology parameters, essentially as described in Cerrone et al., Nat Comm, 2017 or using standard methodologies known in the art. Efficacy in treating disease was assessed by left ventricle ejection fraction percentage (LVEF %) (FIGS. 6A-6D), left ventricle fractional shortening percentage (FS %) (FIGS. 7A-7D), right ventricle area in millimeters squared (RV Area (mm.sup.2)) (FIGS. 8A-8D), right ventricle velocity time integral in millimeters per second (RV VTI (mm/sec)) (FIGS. 9A-9D), and degree of fibrosis (FIGS. 10A-10B). These measures are appropriate functional and morphological indices to evaluate potential efficacy of AAV-mediated PKP2 overexpression in cardiomyocytes as they are among key parameters indicative of ARVC in human disease. Generally, a right ventricle normally has slightly greater amount of fibrosis (irrespective of disease); and this is further exacerbated with lack of PKP2 in the cKO model. Progressive deterioration of these parameters was observed within 21 days of tamoxifen injection, because tamoxifen injection causes myocyte-specific knockout of the PKP gene.

[0247] Evidence for mitigation of the disease phenotype was observed following both AAV9- and AAVrh.74-mediated PKP expression, to varying degrees. With the dose studied to date (3.times.10.sup.13 vg/kg) using a pre-treatment paradigm (AAV 4 weeks prior to tamoxifen-induced PKP cKO), AAV9 surprisingly produced the most robust effects on all parameters. Nevertheless, given the cardiotropism of AAVrh74 and given that biological effects were observed with AAVrh.74-mediated overexpression of PKP2 in this model (e.g. LVEF %, FS %, and right ventricular area), optimization of the dose of AAVrh.74 in combination with the appropriate promoter (i.e., either MHCK7 or hTnnT2) could enable robust therapeutic potential for this vector.

[0248] These results demonstrate both AAV9 and AAVrh.74 can be used to treat PKP2-related diseases, such as Arrhythmogenic right ventricular cardiomyopathy (ARVC) [also known as Arrhythmogenic Right Ventricular Dysplasia (ARVD) or Arrhythmogenic Cardiomyopathy (ACM)] for which the PKP-cKO mouse is considered an appropriate model. Additionally, vectors with either MHCK7 promoter or hTnnT2 promoter have been demonstrated to be effective in treating PKP2-related disease.

Sequence CWU 1 SEQUENCE LISTING <160> NUMBER OF SEQ ID NOS: 96 <210> SEQ ID NO 1 <211> LENGTH: 837 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 1 Met Ala Ala Pro Gly Ala Pro Ala Glu Tyr Gly Tyr Ile Arg Thr Val 1 5 10 15 Leu Gly Gln Gln Ile Leu Gly Gln Leu Asp Ser Ser Ser Leu Ala Leu 20 25 30 Pro Ser Glu Ala Lys Leu Lys Leu Ala Gly Ser Ser Gly Arg Gly Gly 35 40 45 Gln Thr Val Lys Ser Leu Arg Ile Gln Glu Gln Val Gln Gln Thr Leu 50 55 60 Ala Arg Lys Gly Arg Ser Ser Val Gly Asn Gly Asn Leu His Arg Thr 65 70 75 80 Ser Ser Val Pro Glu Tyr Val Tyr Asn Leu His Leu Val Glu Asn Asp 85 90 95 Phe Val Gly Gly Arg Ser Pro Val Pro Lys Thr Tyr Asp Met Leu Lys 100 105 110 Ala Gly Thr Thr Ala Thr Tyr Glu Gly Arg Trp Gly Arg Gly Thr Ala 115 120 125 Gln Tyr Ser Ser Gln Lys Ser Val Glu Glu Arg Ser Leu Arg His Pro 130 135 140 Leu Arg Arg Leu Glu Ile Ser Pro Asp Ser Ser Pro Glu Arg Ala His 145 150 155 160 Tyr Thr His Ser Asp Tyr Gln Tyr Ser Gln Arg Ser Gln Ala Gly His 165 170 175 Thr Leu His His Gln Glu Ser Arg Arg Ala Ala Leu Leu Val Pro Pro 180 185 190 Arg Tyr Ala Arg Ser Glu Ile Val Gly Val Ser Arg Ala Gly Thr Thr 195 200 205 Ser Arg Gln Arg His Phe Asp Thr Tyr His Arg Gln Tyr Gln His Gly 210 215 220 Ser Val Ser Asp Thr Val Phe Asp Ser Ile Pro Ala Asn Pro Ala Leu 225 230 235 240 Leu Thr Tyr Pro Arg Pro Gly Thr Ser Arg Ser Met Gly Asn Leu Leu 245 250 255 Glu Lys Glu Asn Tyr Leu Thr Ala Gly Leu Thr Val Gly Gln Val Arg 260 265 270 Pro Leu Val Pro Leu Gln Pro Val Thr Gln Asn Arg Ala Ser Arg Ser 275 280 285 Ser Trp His Gln Ser Ser Phe His Ser Thr Arg Thr Leu Arg Glu Ala 290 295 300 Gly Pro Ser Val Ala Val Asp Ser Ser Gly Arg Arg Ala His Leu Thr 305 310 315 320 Val Gly Gln Ala Ala Ala Gly Gly Ser Gly Asn Leu Leu Thr Glu Arg 325 330 335 Ser Thr Phe Thr Asp Ser Gln Leu Gly Asn Ala Asp Met Glu Met Thr 340 345 350 Leu Glu Arg Ala Val Ser Met Leu Glu Ala Asp His Met Leu Pro Ser 355 360 365 Arg Ile Ser Ala Ala Ala Thr Phe Ile Gln His Glu Cys Phe Gln Lys 370 375 380 Ser Glu Ala Arg Lys Arg Val Asn Gln Leu Arg Gly Ile Leu Lys Leu 385 390 395 400 Leu Gln Leu Leu Lys Val Gln Asn Glu Asp Val Gln Arg Ala Val Cys 405 410 415 Gly Ala Leu Arg Asn Leu Val Phe Glu Asp Asn Asp Asn Lys Leu Glu 420 425 430 Val Ala Glu Leu Asn Gly Val Pro Arg Leu Leu Gln Val Leu Lys Gln 435 440 445 Thr Arg Asp Leu Glu Thr Lys Lys Gln Ile Thr Gly Leu Leu Trp Asn 450 455 460 Leu Ser Ser Asn Asp Lys Leu Lys Asn Leu Met Ile Thr Glu Ala Leu 465 470 475 480 Leu Thr Leu Thr Glu Asn Ile Ile Ile Pro Phe Ser Gly Trp Pro Glu 485 490 495 Gly Asp Tyr Pro Lys Ala Asn Gly Leu Leu Asp Phe Asp Ile Phe Tyr 500 505 510 Asn Val Thr Gly Cys Leu Arg Asn Met Ser Ser Ala Gly Ala Asp Gly 515 520 525 Arg Lys Ala Met Arg Arg Cys Asp Gly Leu Ile Asp Ser Leu Val His 530 535 540 Tyr Val Arg Gly Thr Ile Ala Asp Tyr Gln Pro Asp Asp Lys Ala Thr 545 550 555 560 Glu Asn Cys Val Cys Ile Leu His Asn Leu Ser Tyr Gln Leu Glu Ala 565 570 575 Glu Leu Pro Glu Lys Tyr Ser Gln Asn Ile Tyr Ile Gln Asn Arg Asn 580 585 590 Ile Gln Thr Asp Asn Asn Lys Ser Ile Gly Cys Phe Gly Ser Arg Ser 595 600 605 Arg Lys Val Lys Glu Gln Tyr Gln Asp Val Pro Met Pro Glu Glu Lys 610 615 620 Ser Asn Pro Lys Gly Val Glu Trp Leu Trp His Ser Ile Val Ile Arg 625 630 635 640 Met Tyr Leu Ser Leu Ile Ala Lys Ser Val Arg Asn Tyr Thr Gln Glu 645 650 655 Ala Ser Leu Gly Ala Leu Gln Asn Leu Thr Ala Gly Ser Gly Pro Met 660 665 670 Pro Thr Ser Val Ala Gln Thr Val Val Gln Lys Glu Ser Gly Leu Gln 675 680 685 His Thr Arg Lys Met Leu His Val Gly Asp Pro Ser Val Lys Lys Thr 690 695 700 Ala Ile Ser Leu Leu Arg Asn Leu Ser Arg Asn Leu Ser Leu Gln Asn 705 710 715 720 Glu Ile Ala Lys Glu Thr Leu Pro Asp Leu Val Ser Ile Ile Pro Asp 725 730 735 Thr Val Pro Ser Thr Asp Leu Leu Ile Glu Thr Thr Ala Ser Ala Cys 740 745 750 Tyr Thr Leu Asn Asn Ile Ile Gln Asn Ser Tyr Gln Asn Ala Arg Asp 755 760 765 Leu Leu Asn Thr Gly Gly Ile Gln Lys Ile Met Ala Ile Ser Ala Gly 770 775 780 Asp Ala Tyr Ala Ser Asn Lys Ala Ser Lys Ala Ala Ser Val Leu Leu 785 790 795 800 Tyr Ser Leu Trp Ala His Thr Glu Leu His His Ala Tyr Lys Lys Ala 805 810 815 Gln Phe Lys Lys Thr Asp Phe Val Asn Ser Arg Thr Ala Lys Ala Tyr 820 825 830 His Ser Leu Lys Asp 835 <210> SEQ ID NO 2 <211> LENGTH: 881 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 2 Met Ala Ala Pro Gly Ala Pro Ala Glu Tyr Gly Tyr Ile Arg Thr Val 1 5 10 15 Leu Gly Gln Gln Ile Leu Gly Gln Leu Asp Ser Ser Ser Leu Ala Leu 20 25 30 Pro Ser Glu Ala Lys Leu Lys Leu Ala Gly Ser Ser Gly Arg Gly Gly 35 40 45 Gln Thr Val Lys Ser Leu Arg Ile Gln Glu Gln Val Gln Gln Thr Leu 50 55 60 Ala Arg Lys Gly Arg Ser Ser Val Gly Asn Gly Asn Leu His Arg Thr 65 70 75 80 Ser Ser Val Pro Glu Tyr Val Tyr Asn Leu His Leu Val Glu Asn Asp 85 90 95 Phe Val Gly Gly Arg Ser Pro Val Pro Lys Thr Tyr Asp Met Leu Lys 100 105 110 Ala Gly Thr Thr Ala Thr Tyr Glu Gly Arg Trp Gly Arg Gly Thr Ala 115 120 125 Gln Tyr Ser Ser Gln Lys Ser Val Glu Glu Arg Ser Leu Arg His Pro 130 135 140 Leu Arg Arg Leu Glu Ile Ser Pro Asp Ser Ser Pro Glu Arg Ala His 145 150 155 160 Tyr Thr His Ser Asp Tyr Gln Tyr Ser Gln Arg Ser Gln Ala Gly His 165 170 175 Thr Leu His His Gln Glu Ser Arg Arg Ala Ala Leu Leu Val Pro Pro 180 185 190 Arg Tyr Ala Arg Ser Glu Ile Val Gly Val Ser Arg Ala Gly Thr Thr 195 200 205 Ser Arg Gln Arg His Phe Asp Thr Tyr His Arg Gln Tyr Gln His Gly 210 215 220 Ser Val Ser Asp Thr Val Phe Asp Ser Ile Pro Ala Asn Pro Ala Leu 225 230 235 240 Leu Thr Tyr Pro Arg Pro Gly Thr Ser Arg Ser Met Gly Asn Leu Leu 245 250 255 Glu Lys Glu Asn Tyr Leu Thr Ala Gly Leu Thr Val Gly Gln Val Arg 260 265 270 Pro Leu Val Pro Leu Gln Pro Val Thr Gln Asn Arg Ala Ser Arg Ser 275 280 285 Ser Trp His Gln Ser Ser Phe His Ser Thr Arg Thr Leu Arg Glu Ala 290 295 300 Gly Pro Ser Val Ala Val Asp Ser Ser Gly Arg Arg Ala His Leu Thr 305 310 315 320 Val Gly Gln Ala Ala Ala Gly Gly Ser Gly Asn Leu Leu Thr Glu Arg 325 330 335 Ser Thr Phe Thr Asp Ser Gln Leu Gly Asn Ala Asp Met Glu Met Thr 340 345 350 Leu Glu Arg Ala Val Ser Met Leu Glu Ala Asp His Met Leu Pro Ser 355 360 365 Arg Ile Ser Ala Ala Ala Thr Phe Ile Gln His Glu Cys Phe Gln Lys 370 375 380 Ser Glu Ala Arg Lys Arg Val Asn Gln Leu Arg Gly Ile Leu Lys Leu 385 390 395 400 Leu Gln Leu Leu Lys Val Gln Asn Glu Asp Val Gln Arg Ala Val Cys 405 410 415 Gly Ala Leu Arg Asn Leu Val Phe Glu Asp Asn Asp Asn Lys Leu Glu 420 425 430 Val Ala Glu Leu Asn Gly Val Pro Arg Leu Leu Gln Val Leu Lys Gln 435 440 445 Thr Arg Asp Leu Glu Thr Lys Lys Gln Ile Thr Asp His Thr Val Asn 450 455 460 Leu Arg Ser Arg Asn Gly Trp Pro Gly Ala Val Ala His Ala Cys Asn 465 470 475 480 Pro Ser Thr Leu Gly Gly Gln Gly Gly Arg Ile Thr Arg Ser Gly Val 485 490 495 Arg Asp Gln Pro Asp Gln His Gly Leu Leu Trp Asn Leu Ser Ser Asn 500 505 510 Asp Lys Leu Lys Asn Leu Met Ile Thr Glu Ala Leu Leu Thr Leu Thr 515 520 525 Glu Asn Ile Ile Ile Pro Phe Ser Gly Trp Pro Glu Gly Asp Tyr Pro 530 535 540 Lys Ala Asn Gly Leu Leu Asp Phe Asp Ile Phe Tyr Asn Val Thr Gly 545 550 555 560 Cys Leu Arg Asn Met Ser Ser Ala Gly Ala Asp Gly Arg Lys Ala Met 565 570 575 Arg Arg Cys Asp Gly Leu Ile Asp Ser Leu Val His Tyr Val Arg Gly 580 585 590 Thr Ile Ala Asp Tyr Gln Pro Asp Asp Lys Ala Thr Glu Asn Cys Val 595 600 605 Cys Ile Leu His Asn Leu Ser Tyr Gln Leu Glu Ala Glu Leu Pro Glu 610 615 620 Lys Tyr Ser Gln Asn Ile Tyr Ile Gln Asn Arg Asn Ile Gln Thr Asp 625 630 635 640 Asn Asn Lys Ser Ile Gly Cys Phe Gly Ser Arg Ser Arg Lys Val Lys 645 650 655 Glu Gln Tyr Gln Asp Val Pro Met Pro Glu Glu Lys Ser Asn Pro Lys 660 665 670 Gly Val Glu Trp Leu Trp His Ser Ile Val Ile Arg Met Tyr Leu Ser 675 680 685 Leu Ile Ala Lys Ser Val Arg Asn Tyr Thr Gln Glu Ala Ser Leu Gly 690 695 700 Ala Leu Gln Asn Leu Thr Ala Gly Ser Gly Pro Met Pro Thr Ser Val 705 710 715 720 Ala Gln Thr Val Val Gln Lys Glu Ser Gly Leu Gln His Thr Arg Lys 725 730 735 Met Leu His Val Gly Asp Pro Ser Val Lys Lys Thr Ala Ile Ser Leu 740 745 750 Leu Arg Asn Leu Ser Arg Asn Leu Ser Leu Gln Asn Glu Ile Ala Lys 755 760 765 Glu Thr Leu Pro Asp Leu Val Ser Ile Ile Pro Asp Thr Val Pro Ser 770 775 780 Thr Asp Leu Leu Ile Glu Thr Thr Ala Ser Ala Cys Tyr Thr Leu Asn 785 790 795 800 Asn Ile Ile Gln Asn Ser Tyr Gln Asn Ala Arg Asp Leu Leu Asn Thr 805 810 815 Gly Gly Ile Gln Lys Ile Met Ala Ile Ser Ala Gly Asp Ala Tyr Ala 820 825 830 Ser Asn Lys Ala Ser Lys Ala Ala Ser Val Leu Leu Tyr Ser Leu Trp 835 840 845 Ala His Thr Glu Leu His His Ala Tyr Lys Lys Ala Gln Phe Lys Lys 850 855 860 Thr Asp Phe Val Asn Ser Arg Thr Ala Lys Ala Tyr His Ser Leu Lys 865 870 875 880 Asp <210> SEQ ID NO 3 <211> LENGTH: 2511 <212> TYPE: DNA <213> ORGANISM: Homo sapiens <400> SEQUENCE: 3 atggcagccc ccggcgcccc agctgagtac ggctacatcc ggaccgtcct gggccagcag 60 atcctgggac aactggacag ctccagcctg gcgctgccct ccgaggccaa gctgaagctg 120 gcggggagca gcggccgcgg cggccagaca gtcaagagcc tgcggatcca ggagcaggtg 180 cagcagaccc tcgcccggaa gggccgcagc tccgtgggca acggaaatct tcaccgaacc 240 agcagtgttc ctgagtatgt ctacaaccta cacttggttg aaaatgattt tgttggaggc 300 cgttcccctg ttcctaaaac ctatgacatg ctaaaggctg gcacaactgc cacttatgaa 360 ggtcgctggg gaagaggaac agcacagtac agctcccaga agtccgtgga agaaaggtcc 420 ttgaggcatc ctctgaggag actggagatt tctcctgaca gcagcccgga gagggctcac 480 tacacgcaca gcgattacca gtacagccag agaagccagg ctgggcacac cctgcaccac 540 caagaaagca ggcgggccgc cctcctagtg ccaccgagat atgctcgttc cgagatcgtg 600 ggggtcagcc gtgctggcac cacaagcagg cagcgccact ttgacacata ccacagacag 660 taccagcatg gctctgttag cgacaccgtt tttgacagca tccctgccaa cccggccctg 720 ctcacgtacc ccaggccagg gaccagccgc agcatgggca acctcttgga gaaggagaac 780 tacctgacgg cagggctcac tgtcgggcag gtcaggccgc tggtgcccct gcagcccgtc 840 actcagaaca gggcttccag gtcctcctgg catcagagct ccttccacag cacccgcacg 900 ctgagggaag ctgggcccag tgtcgccgtg gattccagcg ggaggagagc gcacttgact 960 gtcggccagg cggccgcagg gggaagtggg aatctgctca ctgagagaag cactttcact 1020 gactcccagc tggggaatgc agacatggag atgactctgg agcgagcagt gagtatgctc 1080 gaggcagacc acatgctgcc atccaggatt tctgctgcag ctactttcat acagcacgag 1140 tgcttccaga aatctgaagc tcggaagagg gttaaccagc ttcgtggcat cctcaagctt 1200 ctgcagctcc taaaagttca gaatgaagac gttcagcgag ctgtgtgtgg ggccttgaga 1260 aacttagtat ttgaagacaa tgacaacaaa ttggaggtgg ctgaactaaa tggggtacct 1320 cggctgctcc aggtgctgaa gcaaaccaga gacttggaga ctaaaaaaca aataacaggt 1380 ttgctgtgga atttgtcatc taatgacaaa ctcaagaatc tcatgataac agaagcattg 1440 cttacgctga cggagaatat catcatcccc ttttctgggt ggcctgaagg agactaccca 1500 aaagcaaatg gtttgctcga ttttgacata ttctacaacg tcactggatg cctaagaaac 1560 atgagttctg ctggcgctga tgggagaaaa gcgatgagaa gatgtgacgg actcattgac 1620 tcactggtcc attatgtcag aggaaccatt gcagattacc agccagatga caaggccacg 1680 gagaattgtg tgtgcattct tcataacctc tcctaccagc tggaggcaga gctcccagag 1740 aaatattccc agaatatcta tattcaaaac cggaatatcc agactgacaa caacaaaagt 1800 attggatgtt ttggcagtcg aagcaggaaa gtaaaagagc aataccagga cgtgccgatg 1860 ccggaggaaa agagcaaccc caagggcgtg gagtggctgt ggcattccat tgttataagg 1920 atgtatctgt ccttgatcgc caaaagtgtc cgcaactaca cacaagaagc atccttagga 1980 gctctgcaga acctcacggc cggaagtgga ccaatgccga catcagtggc tcagacagtt 2040 gtccagaagg aaagtggcct gcagcacacc cgaaagatgc tgcatgttgg tgacccaagt 2100 gtgaaaaaga cagccatctc gctgctgagg aatctgtccc ggaatctttc tctgcagaat 2160 gaaattgcca aagaaactct ccctgatttg gtttccatca ttcctgacac agtcccgagt 2220 actgaccttc tcattgaaac tacagcctct gcctgttaca cattgaacaa cataatccaa 2280 aacagttacc agaatgcacg cgaccttcta aacaccgggg gcatccagaa aattatggcc 2340 attagtgcag gcgatgccta tgcctccaac aaagcaagta aagctgcttc cgtccttctg 2400 tattctctgt gggcacacac ggaactgcat catgcctaca agaaggctca gtttaagaag 2460 acagattttg tcaacagccg gactgccaaa gcctaccact cccttaaaga c 2511 <210> SEQ ID NO 4 <211> LENGTH: 2643 <212> TYPE: DNA <213> ORGANISM: Homo sapiens <400> SEQUENCE: 4 atggcagccc ccggcgcccc agctgagtac ggctacatcc ggaccgtcct gggccagcag 60 atcctgggac aactggacag ctccagcctg gcgctgccct ccgaggccaa gctgaagctg 120 gcggggagca gcggccgcgg cggccagaca gtcaagagcc tgcggatcca ggagcaggtg 180 cagcagaccc tcgcccggaa gggccgcagc tccgtgggca acggaaatct tcaccgaacc 240 agcagtgttc ctgagtatgt ctacaaccta cacttggttg aaaatgattt tgttggaggc 300 cgttcccctg ttcctaaaac ctatgacatg ctaaaggctg gcacaactgc cacttatgaa 360 ggtcgctggg gaagaggaac agcacagtac agctcccaga agtccgtgga agaaaggtcc 420 ttgaggcatc ctctgaggag actggagatt tctcctgaca gcagcccgga gagggctcac 480 tacacgcaca gcgattacca gtacagccag agaagccagg ctgggcacac cctgcaccac 540 caagaaagca ggcgggccgc cctcctagtg ccaccgagat atgctcgttc cgagatcgtg 600 ggggtcagcc gtgctggcac cacaagcagg cagcgccact ttgacacata ccacagacag 660 taccagcatg gctctgttag cgacaccgtt tttgacagca tccctgccaa cccggccctg 720 ctcacgtacc ccaggccagg gaccagccgc agcatgggca acctcttgga gaaggagaac 780 tacctgacgg cagggctcac tgtcgggcag gtcaggccgc tggtgcccct gcagcccgtc 840 actcagaaca gggcttccag gtcctcctgg catcagagct ccttccacag cacccgcacg 900 ctgagggaag ctgggcccag tgtcgccgtg gattccagcg ggaggagagc gcacttgact 960 gtcggccagg cggccgcagg gggaagtggg aatctgctca ctgagagaag cactttcact 1020 gactcccagc tggggaatgc agacatggag atgactctgg agcgagcagt gagtatgctc 1080 gaggcagacc acatgctgcc atccaggatt tctgctgcag ctactttcat acagcacgag 1140 tgcttccaga aatctgaagc tcggaagagg gttaaccagc ttcgtggcat cctcaagctt 1200 ctgcagctcc taaaagttca gaatgaagac gttcagcgag ctgtgtgtgg ggccttgaga 1260 aacttagtat ttgaagacaa tgacaacaaa ttggaggtgg ctgaactaaa tggggtacct 1320 cggctgctcc aggtgctgaa gcaaaccaga gacttggaga ctaaaaaaca aataacagac 1380 catacagtca atttaagaag taggaatggc tggccgggcg cggtggctca cgcctgtaat 1440 cccagcactt tgggaggcca aggcgggcgg atcacgaggt caggagttcg agaccagcct 1500 gaccaacatg gtttgctgtg gaatttgtca tctaatgaca aactcaagaa tctcatgata 1560 acagaagcat tgcttacgct gacggagaat atcatcatcc ccttttctgg gtggcctgaa 1620 ggagactacc caaaagcaaa tggtttgctc gattttgaca tattctacaa cgtcactgga 1680 tgcctaagaa acatgagttc tgctggcgct gatgggagaa aagcgatgag aagatgtgac 1740 ggactcattg actcactggt ccattatgtc agaggaacca ttgcagatta ccagccagat 1800 gacaaggcca cggagaattg tgtgtgcatt cttcataacc tctcctacca gctggaggca 1860 gagctcccag agaaatattc ccagaatatc tatattcaaa accggaatat ccagactgac 1920 aacaacaaaa gtattggatg ttttggcagt cgaagcagga aagtaaaaga gcaataccag 1980 gacgtgccga tgccggagga aaagagcaac cccaagggcg tggagtggct gtggcattcc 2040 attgttataa ggatgtatct gtccttgatc gccaaaagtg tccgcaacta cacacaagaa 2100 gcatccttag gagctctgca gaacctcacg gccggaagtg gaccaatgcc gacatcagtg 2160 gctcagacag ttgtccagaa ggaaagtggc ctgcagcaca cccgaaagat gctgcatgtt 2220 ggtgacccaa gtgtgaaaaa gacagccatc tcgctgctga ggaatctgtc ccggaatctt 2280 tctctgcaga atgaaattgc caaagaaact ctccctgatt tggtttccat cattcctgac 2340 acagtcccga gtactgacct tctcattgaa actacagcct ctgcctgtta cacattgaac 2400 aacataatcc aaaacagtta ccagaatgca cgcgaccttc taaacaccgg gggcatccag 2460 aaaattatgg ccattagtgc aggcgatgcc tatgcctcca acaaagcaag taaagctgct 2520 tccgtccttc tgtattctct gtgggcacac acggaactgc atcatgccta caagaaggct 2580 cagtttaaga agacagattt tgtcaacagc cggactgcca aagcctacca ctcccttaaa 2640 gac 2643 <210> SEQ ID NO 5 <211> LENGTH: 10 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Kozak sequence motif <400> SEQUENCE: 5 gccaccatgg 10 <210> SEQ ID NO 6 <211> LENGTH: 2517 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Polynucleotide encoding an PKP2a with Kozak sequence <400> SEQUENCE: 6 gccaccatgg cagcccccgg cgccccagct gagtacggct acatccggac cgtcctgggc 60 cagcagatcc tgggacaact ggacagctcc agcctggcgc tgccctccga ggccaagctg 120 aagctggcgg ggagcagcgg ccgcggcggc cagacagtca agagcctgcg gatccaggag 180 caggtgcagc agaccctcgc ccggaagggc cgcagctccg tgggcaacgg aaatcttcac 240 cgaaccagca gtgttcctga gtatgtctac aacctacact tggttgaaaa tgattttgtt 300 ggaggccgtt cccctgttcc taaaacctat gacatgctaa aggctggcac aactgccact 360 tatgaaggtc gctggggaag aggaacagca cagtacagct cccagaagtc cgtggaagaa 420 aggtccttga ggcatcctct gaggagactg gagatttctc ctgacagcag cccggagagg 480 gctcactaca cgcacagcga ttaccagtac agccagagaa gccaggctgg gcacaccctg 540 caccaccaag aaagcaggcg ggccgccctc ctagtgccac cgagatatgc tcgttccgag 600 atcgtggggg tcagccgtgc tggcaccaca agcaggcagc gccactttga cacataccac 660 agacagtacc agcatggctc tgttagcgac accgtttttg acagcatccc tgccaacccg 720 gccctgctca cgtaccccag gccagggacc agccgcagca tgggcaacct cttggagaag 780 gagaactacc tgacggcagg gctcactgtc gggcaggtca ggccgctggt gcccctgcag 840 cccgtcactc agaacagggc ttccaggtcc tcctggcatc agagctcctt ccacagcacc 900 cgcacgctga gggaagctgg gcccagtgtc gccgtggatt ccagcgggag gagagcgcac 960 ttgactgtcg gccaggcggc cgcaggggga agtgggaatc tgctcactga gagaagcact 1020 ttcactgact cccagctggg gaatgcagac atggagatga ctctggagcg agcagtgagt 1080 atgctcgagg cagaccacat gctgccatcc aggatttctg ctgcagctac tttcatacag 1140 cacgagtgct tccagaaatc tgaagctcgg aagagggtta accagcttcg tggcatcctc 1200 aagcttctgc agctcctaaa agttcagaat gaagacgttc agcgagctgt gtgtggggcc 1260 ttgagaaact tagtatttga agacaatgac aacaaattgg aggtggctga actaaatggg 1320 gtacctcggc tgctccaggt gctgaagcaa accagagact tggagactaa aaaacaaata 1380 acaggtttgc tgtggaattt gtcatctaat gacaaactca agaatctcat gataacagaa 1440 gcattgctta cgctgacgga gaatatcatc atcccctttt ctgggtggcc tgaaggagac 1500 tacccaaaag caaatggttt gctcgatttt gacatattct acaacgtcac tggatgccta 1560 agaaacatga gttctgctgg cgctgatggg agaaaagcga tgagaagatg tgacggactc 1620 attgactcac tggtccatta tgtcagagga accattgcag attaccagcc agatgacaag 1680 gccacggaga attgtgtgtg cattcttcat aacctctcct accagctgga ggcagagctc 1740 ccagagaaat attcccagaa tatctatatt caaaaccgga atatccagac tgacaacaac 1800 aaaagtattg gatgttttgg cagtcgaagc aggaaagtaa aagagcaata ccaggacgtg 1860 ccgatgccgg aggaaaagag caaccccaag ggcgtggagt ggctgtggca ttccattgtt 1920 ataaggatgt atctgtcctt gatcgccaaa agtgtccgca actacacaca agaagcatcc 1980 ttaggagctc tgcagaacct cacggccgga agtggaccaa tgccgacatc agtggctcag 2040 acagttgtcc agaaggaaag tggcctgcag cacacccgaa agatgctgca tgttggtgac 2100 ccaagtgtga aaaagacagc catctcgctg ctgaggaatc tgtcccggaa tctttctctg 2160 cagaatgaaa ttgccaaaga aactctccct gatttggttt ccatcattcc tgacacagtc 2220 ccgagtactg accttctcat tgaaactaca gcctctgcct gttacacatt gaacaacata 2280 atccaaaaca gttaccagaa tgcacgcgac cttctaaaca ccgggggcat ccagaaaatt 2340 atggccatta gtgcaggcga tgcctatgcc tccaacaaag caagtaaagc tgcttccgtc 2400 cttctgtatt ctctgtgggc acacacggaa ctgcatcatg cctacaagaa ggctcagttt 2460 aagaagacag attttgtcaa cagccggact gccaaagcct accactccct taaagac 2517 <210> SEQ ID NO 7 <211> LENGTH: 2649 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Polynucleotide encoding an PKP2b with Kozak sequence <400> SEQUENCE: 7 gccaccatgg cagcccccgg cgccccagct gagtacggct acatccggac cgtcctgggc 60 cagcagatcc tgggacaact ggacagctcc agcctggcgc tgccctccga ggccaagctg 120 aagctggcgg ggagcagcgg ccgcggcggc cagacagtca agagcctgcg gatccaggag 180 caggtgcagc agaccctcgc ccggaagggc cgcagctccg tgggcaacgg aaatcttcac 240 cgaaccagca gtgttcctga gtatgtctac aacctacact tggttgaaaa tgattttgtt 300 ggaggccgtt cccctgttcc taaaacctat gacatgctaa aggctggcac aactgccact 360 tatgaaggtc gctggggaag aggaacagca cagtacagct cccagaagtc cgtggaagaa 420 aggtccttga ggcatcctct gaggagactg gagatttctc ctgacagcag cccggagagg 480 gctcactaca cgcacagcga ttaccagtac agccagagaa gccaggctgg gcacaccctg 540 caccaccaag aaagcaggcg ggccgccctc ctagtgccac cgagatatgc tcgttccgag 600 atcgtggggg tcagccgtgc tggcaccaca agcaggcagc gccactttga cacataccac 660 agacagtacc agcatggctc tgttagcgac accgtttttg acagcatccc tgccaacccg 720 gccctgctca cgtaccccag gccagggacc agccgcagca tgggcaacct cttggagaag 780 gagaactacc tgacggcagg gctcactgtc gggcaggtca ggccgctggt gcccctgcag 840 cccgtcactc agaacagggc ttccaggtcc tcctggcatc agagctcctt ccacagcacc 900 cgcacgctga gggaagctgg gcccagtgtc gccgtggatt ccagcgggag gagagcgcac 960 ttgactgtcg gccaggcggc cgcaggggga agtgggaatc tgctcactga gagaagcact 1020 ttcactgact cccagctggg gaatgcagac atggagatga ctctggagcg agcagtgagt 1080 atgctcgagg cagaccacat gctgccatcc aggatttctg ctgcagctac tttcatacag 1140 cacgagtgct tccagaaatc tgaagctcgg aagagggtta accagcttcg tggcatcctc 1200 aagcttctgc agctcctaaa agttcagaat gaagacgttc agcgagctgt gtgtggggcc 1260 ttgagaaact tagtatttga agacaatgac aacaaattgg aggtggctga actaaatggg 1320 gtacctcggc tgctccaggt gctgaagcaa accagagact tggagactaa aaaacaaata 1380 acagaccata cagtcaattt aagaagtagg aatggctggc cgggcgcggt ggctcacgcc 1440 tgtaatccca gcactttggg aggccaaggc gggcggatca cgaggtcagg agttcgagac 1500 cagcctgacc aacatggttt gctgtggaat ttgtcatcta atgacaaact caagaatctc 1560 atgataacag aagcattgct tacgctgacg gagaatatca tcatcccctt ttctgggtgg 1620 cctgaaggag actacccaaa agcaaatggt ttgctcgatt ttgacatatt ctacaacgtc 1680 actggatgcc taagaaacat gagttctgct ggcgctgatg ggagaaaagc gatgagaaga 1740 tgtgacggac tcattgactc actggtccat tatgtcagag gaaccattgc agattaccag 1800 ccagatgaca aggccacgga gaattgtgtg tgcattcttc ataacctctc ctaccagctg 1860 gaggcagagc tcccagagaa atattcccag aatatctata ttcaaaaccg gaatatccag 1920 actgacaaca acaaaagtat tggatgtttt ggcagtcgaa gcaggaaagt aaaagagcaa 1980 taccaggacg tgccgatgcc ggaggaaaag agcaacccca agggcgtgga gtggctgtgg 2040 cattccattg ttataaggat gtatctgtcc ttgatcgcca aaagtgtccg caactacaca 2100 caagaagcat ccttaggagc tctgcagaac ctcacggccg gaagtggacc aatgccgaca 2160 tcagtggctc agacagttgt ccagaaggaa agtggcctgc agcacacccg aaagatgctg 2220 catgttggtg acccaagtgt gaaaaagaca gccatctcgc tgctgaggaa tctgtcccgg 2280 aatctttctc tgcagaatga aattgccaaa gaaactctcc ctgatttggt ttccatcatt 2340 cctgacacag tcccgagtac tgaccttctc attgaaacta cagcctctgc ctgttacaca 2400 ttgaacaaca taatccaaaa cagttaccag aatgcacgcg accttctaaa caccgggggc 2460 atccagaaaa ttatggccat tagtgcaggc gatgcctatg cctccaacaa agcaagtaaa 2520 gctgcttccg tccttctgta ttctctgtgg gcacacacgg aactgcatca tgcctacaag 2580 aaggctcagt ttaagaagac agattttgtc aacagccgga ctgccaaagc ctaccactcc 2640 cttaaagac 2649 <210> SEQ ID NO 8 <211> LENGTH: 4081 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Made in Lab - MHCK7-PKP2a expression cassette <400> SEQUENCE: 8 acccttcaga ttaaaaataa ctgaggtaag ggcctgggta ggggaggtgg tgtgagacgc 60 tcctgtctct cctctatctg cccatcggcc ctttggggag gaggaatgtg cccaaggact 120 aaaaaaaggc catggagcca gaggggcgag ggcaacagac ctttcatggg caaaccttgg 180 ggccctgctg tctagcatgc cccactacgg gtctaggctg cccatgtaag gaggcaaggc 240 ctggggacac ccgagatgcc tggttataat taacccagac atgtggctgc cccccccccc 300 ccaacacctg ctgcctctaa aaataaccct gtccctggtg gatcccctgc atgcgaagat 360 cttcgaacaa ggctgtgggg gactgagggc aggctgtaac aggcttgggg gccagggctt 420 atacgtgcct gggactccca aagtattact gttccatgtt cccggcgaag ggccagctgt 480 cccccgccag ctagactcag cacttagttt aggaaccagt gagcaagtca gcccttgggg 540 cagcccatac aaggccatgg ggctgggcaa gctgcacgcc tgggtccggg gtgggcacgg 600 tgcccgggca acgagctgaa agctcatctg ctctcagggg cccctccctg gggacagccc 660 ctcctggcta gtcacaccct gtaggctcct ctatataacc caggggcaca ggggctgccc 720 tcattctacc accacctcca cagcacagac agacactcag gagccagcca ggccaccatg 780 gcagcccccg gcgccccagc tgagtacggc tacatccgga ccgtcctggg ccagcagatc 840 ctgggacaac tggacagctc cagcctggcg ctgccctccg aggccaagct gaagctggcg 900 gggagcagcg gccgcggcgg ccagacagtc aagagcctgc ggatccagga gcaggtgcag 960 cagaccctcg cccggaaggg ccgcagctcc gtgggcaacg gaaatcttca ccgaaccagc 1020 agtgttcctg agtatgtcta caacctacac ttggttgaaa atgattttgt tggaggccgt 1080 tcccctgttc ctaaaaccta tgacatgcta aaggctggca caactgccac ttatgaaggt 1140 cgctggggaa gaggaacagc acagtacagc tcccagaagt ccgtggaaga aaggtccttg 1200 aggcatcctc tgaggagact ggagatttct cctgacagca gcccggagag ggctcactac 1260 acgcacagcg attaccagta cagccagaga agccaggctg ggcacaccct gcaccaccaa 1320 gaaagcaggc gggccgccct cctagtgcca ccgagatatg ctcgttccga gatcgtgggg 1380 gtcagccgtg ctggcaccac aagcaggcag cgccactttg acacatacca cagacagtac 1440 cagcatggct ctgttagcga caccgttttt gacagcatcc ctgccaaccc ggccctgctc 1500 acgtacccca ggccagggac cagccgcagc atgggcaacc tcttggagaa ggagaactac 1560 ctgacggcag ggctcactgt cgggcaggtc aggccgctgg tgcccctgca gcccgtcact 1620 cagaacaggg cttccaggtc ctcctggcat cagagctcct tccacagcac ccgcacgctg 1680 agggaagctg ggcccagtgt cgccgtggat tccagcggga ggagagcgca cttgactgtc 1740 ggccaggcgg ccgcaggggg aagtgggaat ctgctcactg agagaagcac tttcactgac 1800 tcccagctgg ggaatgcaga catggagatg actctggagc gagcagtgag tatgctcgag 1860 gcagaccaca tgctgccatc caggatttct gctgcagcta ctttcataca gcacgagtgc 1920 ttccagaaat ctgaagctcg gaagagggtt aaccagcttc gtggcatcct caagcttctg 1980 cagctcctaa aagttcagaa tgaagacgtt cagcgagctg tgtgtggggc cttgagaaac 2040 ttagtatttg aagacaatga caacaaattg gaggtggctg aactaaatgg ggtacctcgg 2100 ctgctccagg tgctgaagca aaccagagac ttggagacta aaaaacaaat aacaggtttg 2160 ctgtggaatt tgtcatctaa tgacaaactc aagaatctca tgataacaga agcattgctt 2220 acgctgacgg agaatatcat catccccttt tctgggtggc ctgaaggaga ctacccaaaa 2280 gcaaatggtt tgctcgattt tgacatattc tacaacgtca ctggatgcct aagaaacatg 2340 agttctgctg gcgctgatgg gagaaaagcg atgagaagat gtgacggact cattgactca 2400 ctggtccatt atgtcagagg aaccattgca gattaccagc cagatgacaa ggccacggag 2460 aattgtgtgt gcattcttca taacctctcc taccagctgg aggcagagct cccagagaaa 2520 tattcccaga atatctatat tcaaaaccgg aatatccaga ctgacaacaa caaaagtatt 2580 ggatgttttg gcagtcgaag caggaaagta aaagagcaat accaggacgt gccgatgccg 2640 gaggaaaaga gcaaccccaa gggcgtggag tggctgtggc attccattgt tataaggatg 2700 tatctgtcct tgatcgccaa aagtgtccgc aactacacac aagaagcatc cttaggagct 2760 ctgcagaacc tcacggccgg aagtggacca atgccgacat cagtggctca gacagttgtc 2820 cagaaggaaa gtggcctgca gcacacccga aagatgctgc atgttggtga cccaagtgtg 2880 aaaaagacag ccatctcgct gctgaggaat ctgtcccgga atctttctct gcagaatgaa 2940 attgccaaag aaactctccc tgatttggtt tccatcattc ctgacacagt cccgagtact 3000 gaccttctca ttgaaactac agcctctgcc tgttacacat tgaacaacat aatccaaaac 3060 agttaccaga atgcacgcga ccttctaaac accgggggca tccagaaaat tatggccatt 3120 agtgcaggcg atgcctatgc ctccaacaaa gcaagtaaag ctgcttccgt ccttctgtat 3180 tctctgtggg cacacacgga actgcatcat gcctacaaga aggctcagtt taagaagaca 3240 gattttgtca acagccggac tgccaaagcc taccactccc ttaaagactg atcaacctct 3300 ggattacaaa atttgtgaaa gattgactgg tattcttaac tatgttgctc cttttacgct 3360 atgtggatac gctgctttaa tgcctttgta tcatgctatt gcttcccgta tggctttcat 3420 tttctcctcc ttgtataaat cctggttgct gtctctttat gaggagttgt ggcccgttgt 3480 caggcaacgt ggcgtggtgt gcactgtgtt tgctgacgca acccccactg gttggggcat 3540 tgccaccacc tgtcagctcc tttccgggac tttcgctttc cccctcccta ttgccacggc 3600 ggaactcatc gccgcctgcc ttgcccgctg ctggacaggg gctcggctgt tgggcactga 3660 caattccgtg gtgttgtcgg ggaaatcatc gtcctttcct tggctgctcg cctgtgttgc 3720 cacctggatt ctgcgcggga cgtccttctg ctacgtccct tcggccctca atccagcgga 3780 ccttccttcc cgcggcctgc tgccggctct gcggcctctt ccgcgtcttc gccttcgccc 3840 tcagacgagt cggatctccc tttgggccgc ctccccgcac tgcccgggtg gcatccctgt 3900 gacccctccc cagtgcctct cctggccctg gaagttgcca ctccagtgcc caccagcctt 3960 gtcctaataa aattaagttg catcattttg tctgactagg tgtccttcta taatattatg 4020 gggtggaggg gggtggtatg gagcaagggg cccaagttgg gaagaaacct gtagggcctg 4080 c 4081 <210> SEQ ID NO 9 <211> LENGTH: 3854 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Made in lab - hTnT-PKP2a expression cassette <400> SEQUENCE: 9 ctcagtccat taggagccag tagcctggaa gatgtcttta cccccagcat cagttcaagt 60 ggagcagcac ataactcttg ccctctgcct tccaagattc tggtgctgag acttatggag 120 tgtcttggag gttgccttct gccccccaac cctgctccca gctggccctc ccaggcctgg 180 gttgctggcc tctgctttat caggattctc aagagggaca gctggtttat gttgcatgac 240 tgttccctgc atatctgctc tggttttaaa tagcttatct gagcagctgg aggaccacat 300 gggcttatat ggcgtggggt acatgttcct gtagccttgt ccctggcacc tgccaaaata 360 gcagccaaca ccccccaccc ccaccgccat ccccctgccc cacccgtccc ctgtcgcaca 420 ttcctccctc cgcagggctg gctcaccagg ccccagccca catgcctgct taaagccctc 480 tccatcctct gcctcaccca gtccccgctg agactgagca gacgcctcca ggatctgtcg 540 gcaggccacc atggcagccc ccggcgcccc agctgagtac ggctacatcc ggaccgtcct 600 gggccagcag atcctgggac aactggacag ctccagcctg gcgctgccct ccgaggccaa 660 gctgaagctg gcggggagca gcggccgcgg cggccagaca gtcaagagcc tgcggatcca 720 ggagcaggtg cagcagaccc tcgcccggaa gggccgcagc tccgtgggca acggaaatct 780 tcaccgaacc agcagtgttc ctgagtatgt ctacaaccta cacttggttg aaaatgattt 840 tgttggaggc cgttcccctg ttcctaaaac ctatgacatg ctaaaggctg gcacaactgc 900 cacttatgaa ggtcgctggg gaagaggaac agcacagtac agctcccaga agtccgtgga 960 agaaaggtcc ttgaggcatc ctctgaggag actggagatt tctcctgaca gcagcccgga 1020 gagggctcac tacacgcaca gcgattacca gtacagccag agaagccagg ctgggcacac 1080 cctgcaccac caagaaagca ggcgggccgc cctcctagtg ccaccgagat atgctcgttc 1140 cgagatcgtg ggggtcagcc gtgctggcac cacaagcagg cagcgccact ttgacacata 1200 ccacagacag taccagcatg gctctgttag cgacaccgtt tttgacagca tccctgccaa 1260 cccggccctg ctcacgtacc ccaggccagg gaccagccgc agcatgggca acctcttgga 1320 gaaggagaac tacctgacgg cagggctcac tgtcgggcag gtcaggccgc tggtgcccct 1380 gcagcccgtc actcagaaca gggcttccag gtcctcctgg catcagagct ccttccacag 1440 cacccgcacg ctgagggaag ctgggcccag tgtcgccgtg gattccagcg ggaggagagc 1500 gcacttgact gtcggccagg cggccgcagg gggaagtggg aatctgctca ctgagagaag 1560 cactttcact gactcccagc tggggaatgc agacatggag atgactctgg agcgagcagt 1620 gagtatgctc gaggcagacc acatgctgcc atccaggatt tctgctgcag ctactttcat 1680 acagcacgag tgcttccaga aatctgaagc tcggaagagg gttaaccagc ttcgtggcat 1740 cctcaagctt ctgcagctcc taaaagttca gaatgaagac gttcagcgag ctgtgtgtgg 1800 ggccttgaga aacttagtat ttgaagacaa tgacaacaaa ttggaggtgg ctgaactaaa 1860 tggggtacct cggctgctcc aggtgctgaa gcaaaccaga gacttggaga ctaaaaaaca 1920 aataacaggt ttgctgtgga atttgtcatc taatgacaaa ctcaagaatc tcatgataac 1980 agaagcattg cttacgctga cggagaatat catcatcccc ttttctgggt ggcctgaagg 2040 agactaccca aaagcaaatg gtttgctcga ttttgacata ttctacaacg tcactggatg 2100 cctaagaaac atgagttctg ctggcgctga tgggagaaaa gcgatgagaa gatgtgacgg 2160 actcattgac tcactggtcc attatgtcag aggaaccatt gcagattacc agccagatga 2220 caaggccacg gagaattgtg tgtgcattct tcataacctc tcctaccagc tggaggcaga 2280 gctcccagag aaatattccc agaatatcta tattcaaaac cggaatatcc agactgacaa 2340 caacaaaagt attggatgtt ttggcagtcg aagcaggaaa gtaaaagagc aataccagga 2400 cgtgccgatg ccggaggaaa agagcaaccc caagggcgtg gagtggctgt ggcattccat 2460 tgttataagg atgtatctgt ccttgatcgc caaaagtgtc cgcaactaca cacaagaagc 2520 atccttagga gctctgcaga acctcacggc cggaagtgga ccaatgccga catcagtggc 2580 tcagacagtt gtccagaagg aaagtggcct gcagcacacc cgaaagatgc tgcatgttgg 2640 tgacccaagt gtgaaaaaga cagccatctc gctgctgagg aatctgtccc ggaatctttc 2700 tctgcagaat gaaattgcca aagaaactct ccctgatttg gtttccatca ttcctgacac 2760 agtcccgagt actgaccttc tcattgaaac tacagcctct gcctgttaca cattgaacaa 2820 cataatccaa aacagttacc agaatgcacg cgaccttcta aacaccgggg gcatccagaa 2880 aattatggcc attagtgcag gcgatgccta tgcctccaac aaagcaagta aagctgcttc 2940 cgtccttctg tattctctgt gggcacacac ggaactgcat catgcctaca agaaggctca 3000 gtttaagaag acagattttg tcaacagccg gactgccaaa gcctaccact cccttaaaga 3060 ctgatcaacc tctggattac aaaatttgtg aaagattgac tggtattctt aactatgttg 3120 ctccttttac gctatgtgga tacgctgctt taatgccttt gtatcatgct attgcttccc 3180 gtatggcttt cattttctcc tccttgtata aatcctggtt gctgtctctt tatgaggagt 3240 tgtggcccgt tgtcaggcaa cgtggcgtgg tgtgcactgt gtttgctgac gcaaccccca 3300 ctggttgggg cattgccacc acctgtcagc tcctttccgg gactttcgct ttccccctcc 3360 ctattgccac ggcggaactc atcgccgcct gccttgcccg ctgctggaca ggggctcggc 3420 tgttgggcac tgacaattcc gtggtgttgt cggggaaatc atcgtccttt ccttggctgc 3480 tcgcctgtgt tgccacctgg attctgcgcg ggacgtcctt ctgctacgtc ccttcggccc 3540 tcaatccagc ggaccttcct tcccgcggcc tgctgccggc tctgcggcct cttccgcgtc 3600 ttcgccttcg ccctcagacg agtcggatct ccctttgggc cgcctccccg cactgcccgg 3660 gtggcatccc tgtgacccct ccccagtgcc tctcctggcc ctggaagttg ccactccagt 3720 gcccaccagc cttgtcctaa taaaattaag ttgcatcatt ttgtctgact aggtgtcctt 3780 ctataatatt atggggtgga ggggggtggt atggagcaag gggcccaagt tgggaagaaa 3840 cctgtagggc ctgc 3854 <210> SEQ ID NO 10 <211> LENGTH: 4213 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Made in Lab - MHCK7-PKP2b expression cassette <400> SEQUENCE: 10 acccttcaga ttaaaaataa ctgaggtaag ggcctgggta ggggaggtgg tgtgagacgc 60 tcctgtctct cctctatctg cccatcggcc ctttggggag gaggaatgtg cccaaggact 120 aaaaaaaggc catggagcca gaggggcgag ggcaacagac ctttcatggg caaaccttgg 180 ggccctgctg tctagcatgc cccactacgg gtctaggctg cccatgtaag gaggcaaggc 240 ctggggacac ccgagatgcc tggttataat taacccagac atgtggctgc cccccccccc 300 ccaacacctg ctgcctctaa aaataaccct gtccctggtg gatcccctgc atgcgaagat 360 cttcgaacaa ggctgtgggg gactgagggc aggctgtaac aggcttgggg gccagggctt 420 atacgtgcct gggactccca aagtattact gttccatgtt cccggcgaag ggccagctgt 480 cccccgccag ctagactcag cacttagttt aggaaccagt gagcaagtca gcccttgggg 540 cagcccatac aaggccatgg ggctgggcaa gctgcacgcc tgggtccggg gtgggcacgg 600 tgcccgggca acgagctgaa agctcatctg ctctcagggg cccctccctg gggacagccc 660 ctcctggcta gtcacaccct gtaggctcct ctatataacc caggggcaca ggggctgccc 720 tcattctacc accacctcca cagcacagac agacactcag gagccagcca ggccaccatg 780 gcagcccccg gcgccccagc tgagtacggc tacatccgga ccgtcctggg ccagcagatc 840 ctgggacaac tggacagctc cagcctggcg ctgccctccg aggccaagct gaagctggcg 900 gggagcagcg gccgcggcgg ccagacagtc aagagcctgc ggatccagga gcaggtgcag 960 cagaccctcg cccggaaggg ccgcagctcc gtgggcaacg gaaatcttca ccgaaccagc 1020 agtgttcctg agtatgtcta caacctacac ttggttgaaa atgattttgt tggaggccgt 1080 tcccctgttc ctaaaaccta tgacatgcta aaggctggca caactgccac ttatgaaggt 1140 cgctggggaa gaggaacagc acagtacagc tcccagaagt ccgtggaaga aaggtccttg 1200 aggcatcctc tgaggagact ggagatttct cctgacagca gcccggagag ggctcactac 1260 acgcacagcg attaccagta cagccagaga agccaggctg ggcacaccct gcaccaccaa 1320 gaaagcaggc gggccgccct cctagtgcca ccgagatatg ctcgttccga gatcgtgggg 1380 gtcagccgtg ctggcaccac aagcaggcag cgccactttg acacatacca cagacagtac 1440 cagcatggct ctgttagcga caccgttttt gacagcatcc ctgccaaccc ggccctgctc 1500 acgtacccca ggccagggac cagccgcagc atgggcaacc tcttggagaa ggagaactac 1560 ctgacggcag ggctcactgt cgggcaggtc aggccgctgg tgcccctgca gcccgtcact 1620 cagaacaggg cttccaggtc ctcctggcat cagagctcct tccacagcac ccgcacgctg 1680 agggaagctg ggcccagtgt cgccgtggat tccagcggga ggagagcgca cttgactgtc 1740 ggccaggcgg ccgcaggggg aagtgggaat ctgctcactg agagaagcac tttcactgac 1800 tcccagctgg ggaatgcaga catggagatg actctggagc gagcagtgag tatgctcgag 1860 gcagaccaca tgctgccatc caggatttct gctgcagcta ctttcataca gcacgagtgc 1920 ttccagaaat ctgaagctcg gaagagggtt aaccagcttc gtggcatcct caagcttctg 1980 cagctcctaa aagttcagaa tgaagacgtt cagcgagctg tgtgtggggc cttgagaaac 2040 ttagtatttg aagacaatga caacaaattg gaggtggctg aactaaatgg ggtacctcgg 2100 ctgctccagg tgctgaagca aaccagagac ttggagacta aaaaacaaat aacagaccat 2160 acagtcaatt taagaagtag gaatggctgg ccgggcgcgg tggctcacgc ctgtaatccc 2220 agcactttgg gaggccaagg cgggcggatc acgaggtcag gagttcgaga ccagcctgac 2280 caacatggtt tgctgtggaa tttgtcatct aatgacaaac tcaagaatct catgataaca 2340 gaagcattgc ttacgctgac ggagaatatc atcatcccct tttctgggtg gcctgaagga 2400 gactacccaa aagcaaatgg tttgctcgat tttgacatat tctacaacgt cactggatgc 2460 ctaagaaaca tgagttctgc tggcgctgat gggagaaaag cgatgagaag atgtgacgga 2520 ctcattgact cactggtcca ttatgtcaga ggaaccattg cagattacca gccagatgac 2580 aaggccacgg agaattgtgt gtgcattctt cataacctct cctaccagct ggaggcagag 2640 ctcccagaga aatattccca gaatatctat attcaaaacc ggaatatcca gactgacaac 2700 aacaaaagta ttggatgttt tggcagtcga agcaggaaag taaaagagca ataccaggac 2760 gtgccgatgc cggaggaaaa gagcaacccc aagggcgtgg agtggctgtg gcattccatt 2820 gttataagga tgtatctgtc cttgatcgcc aaaagtgtcc gcaactacac acaagaagca 2880 tccttaggag ctctgcagaa cctcacggcc ggaagtggac caatgccgac atcagtggct 2940 cagacagttg tccagaagga aagtggcctg cagcacaccc gaaagatgct gcatgttggt 3000 gacccaagtg tgaaaaagac agccatctcg ctgctgagga atctgtcccg gaatctttct 3060 ctgcagaatg aaattgccaa agaaactctc cctgatttgg tttccatcat tcctgacaca 3120 gtcccgagta ctgaccttct cattgaaact acagcctctg cctgttacac attgaacaac 3180 ataatccaaa acagttacca gaatgcacgc gaccttctaa acaccggggg catccagaaa 3240 attatggcca ttagtgcagg cgatgcctat gcctccaaca aagcaagtaa agctgcttcc 3300 gtccttctgt attctctgtg ggcacacacg gaactgcatc atgcctacaa gaaggctcag 3360 tttaagaaga cagattttgt caacagccgg actgccaaag cctaccactc ccttaaagac 3420 tgatcaacct ctggattaca aaatttgtga aagattgact ggtattctta actatgttgc 3480 tccttttacg ctatgtggat acgctgcttt aatgcctttg tatcatgcta ttgcttcccg 3540 tatggctttc attttctcct ccttgtataa atcctggttg ctgtctcttt atgaggagtt 3600 gtggcccgtt gtcaggcaac gtggcgtggt gtgcactgtg tttgctgacg caacccccac 3660 tggttggggc attgccacca cctgtcagct cctttccggg actttcgctt tccccctccc 3720 tattgccacg gcggaactca tcgccgcctg ccttgcccgc tgctggacag gggctcggct 3780 gttgggcact gacaattccg tggtgttgtc ggggaaatca tcgtcctttc cttggctgct 3840 cgcctgtgtt gccacctgga ttctgcgcgg gacgtccttc tgctacgtcc cttcggccct 3900 caatccagcg gaccttcctt cccgcggcct gctgccggct ctgcggcctc ttccgcgtct 3960 tcgccttcgc cctcagacga gtcggatctc cctttgggcc gcctccccgc actgcccggg 4020 tggcatccct gtgacccctc cccagtgcct ctcctggccc tggaagttgc cactccagtg 4080 cccaccagcc ttgtcctaat aaaattaagt tgcatcattt tgtctgacta ggtgtccttc 4140 tataatatta tggggtggag gggggtggta tggagcaagg ggcccaagtt gggaagaaac 4200 ctgtagggcc tgc 4213 <210> SEQ ID NO 11 <211> LENGTH: 3986 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Made in Lab - hTnT-PKP2b express cassette <400> SEQUENCE: 11 ctcagtccat taggagccag tagcctggaa gatgtcttta cccccagcat cagttcaagt 60 ggagcagcac ataactcttg ccctctgcct tccaagattc tggtgctgag acttatggag 120 tgtcttggag gttgccttct gccccccaac cctgctccca gctggccctc ccaggcctgg 180 gttgctggcc tctgctttat caggattctc aagagggaca gctggtttat gttgcatgac 240 tgttccctgc atatctgctc tggttttaaa tagcttatct gagcagctgg aggaccacat 300 gggcttatat ggcgtggggt acatgttcct gtagccttgt ccctggcacc tgccaaaata 360 gcagccaaca ccccccaccc ccaccgccat ccccctgccc cacccgtccc ctgtcgcaca 420 ttcctccctc cgcagggctg gctcaccagg ccccagccca catgcctgct taaagccctc 480 tccatcctct gcctcaccca gtccccgctg agactgagca gacgcctcca ggatctgtcg 540 gcaggccacc atggcagccc ccggcgcccc agctgagtac ggctacatcc ggaccgtcct 600 gggccagcag atcctgggac aactggacag ctccagcctg gcgctgccct ccgaggccaa 660 gctgaagctg gcggggagca gcggccgcgg cggccagaca gtcaagagcc tgcggatcca 720 ggagcaggtg cagcagaccc tcgcccggaa gggccgcagc tccgtgggca acggaaatct 780 tcaccgaacc agcagtgttc ctgagtatgt ctacaaccta cacttggttg aaaatgattt 840 tgttggaggc cgttcccctg ttcctaaaac ctatgacatg ctaaaggctg gcacaactgc 900 cacttatgaa ggtcgctggg gaagaggaac agcacagtac agctcccaga agtccgtgga 960 agaaaggtcc ttgaggcatc ctctgaggag actggagatt tctcctgaca gcagcccgga 1020 gagggctcac tacacgcaca gcgattacca gtacagccag agaagccagg ctgggcacac 1080 cctgcaccac caagaaagca ggcgggccgc cctcctagtg ccaccgagat atgctcgttc 1140 cgagatcgtg ggggtcagcc gtgctggcac cacaagcagg cagcgccact ttgacacata 1200 ccacagacag taccagcatg gctctgttag cgacaccgtt tttgacagca tccctgccaa 1260 cccggccctg ctcacgtacc ccaggccagg gaccagccgc agcatgggca acctcttgga 1320 gaaggagaac tacctgacgg cagggctcac tgtcgggcag gtcaggccgc tggtgcccct 1380 gcagcccgtc actcagaaca gggcttccag gtcctcctgg catcagagct ccttccacag 1440 cacccgcacg ctgagggaag ctgggcccag tgtcgccgtg gattccagcg ggaggagagc 1500 gcacttgact gtcggccagg cggccgcagg gggaagtggg aatctgctca ctgagagaag 1560 cactttcact gactcccagc tggggaatgc agacatggag atgactctgg agcgagcagt 1620 gagtatgctc gaggcagacc acatgctgcc atccaggatt tctgctgcag ctactttcat 1680 acagcacgag tgcttccaga aatctgaagc tcggaagagg gttaaccagc ttcgtggcat 1740 cctcaagctt ctgcagctcc taaaagttca gaatgaagac gttcagcgag ctgtgtgtgg 1800 ggccttgaga aacttagtat ttgaagacaa tgacaacaaa ttggaggtgg ctgaactaaa 1860 tggggtacct cggctgctcc aggtgctgaa gcaaaccaga gacttggaga ctaaaaaaca 1920 aataacagac catacagtca atttaagaag taggaatggc tggccgggcg cggtggctca 1980 cgcctgtaat cccagcactt tgggaggcca aggcgggcgg atcacgaggt caggagttcg 2040 agaccagcct gaccaacatg gtttgctgtg gaatttgtca tctaatgaca aactcaagaa 2100 tctcatgata acagaagcat tgcttacgct gacggagaat atcatcatcc ccttttctgg 2160 gtggcctgaa ggagactacc caaaagcaaa tggtttgctc gattttgaca tattctacaa 2220 cgtcactgga tgcctaagaa acatgagttc tgctggcgct gatgggagaa aagcgatgag 2280 aagatgtgac ggactcattg actcactggt ccattatgtc agaggaacca ttgcagatta 2340 ccagccagat gacaaggcca cggagaattg tgtgtgcatt cttcataacc tctcctacca 2400 gctggaggca gagctcccag agaaatattc ccagaatatc tatattcaaa accggaatat 2460 ccagactgac aacaacaaaa gtattggatg ttttggcagt cgaagcagga aagtaaaaga 2520 gcaataccag gacgtgccga tgccggagga aaagagcaac cccaagggcg tggagtggct 2580 gtggcattcc attgttataa ggatgtatct gtccttgatc gccaaaagtg tccgcaacta 2640 cacacaagaa gcatccttag gagctctgca gaacctcacg gccggaagtg gaccaatgcc 2700 gacatcagtg gctcagacag ttgtccagaa ggaaagtggc ctgcagcaca cccgaaagat 2760 gctgcatgtt ggtgacccaa gtgtgaaaaa gacagccatc tcgctgctga ggaatctgtc 2820 ccggaatctt tctctgcaga atgaaattgc caaagaaact ctccctgatt tggtttccat 2880 cattcctgac acagtcccga gtactgacct tctcattgaa actacagcct ctgcctgtta 2940 cacattgaac aacataatcc aaaacagtta ccagaatgca cgcgaccttc taaacaccgg 3000 gggcatccag aaaattatgg ccattagtgc aggcgatgcc tatgcctcca acaaagcaag 3060 taaagctgct tccgtccttc tgtattctct gtgggcacac acggaactgc atcatgccta 3120 caagaaggct cagtttaaga agacagattt tgtcaacagc cggactgcca aagcctacca 3180 ctcccttaaa gactgatcaa cctctggatt acaaaatttg tgaaagattg actggtattc 3240 ttaactatgt tgctcctttt acgctatgtg gatacgctgc tttaatgcct ttgtatcatg 3300 ctattgcttc ccgtatggct ttcattttct cctccttgta taaatcctgg ttgctgtctc 3360 tttatgagga gttgtggccc gttgtcaggc aacgtggcgt ggtgtgcact gtgtttgctg 3420 acgcaacccc cactggttgg ggcattgcca ccacctgtca gctcctttcc gggactttcg 3480 ctttccccct ccctattgcc acggcggaac tcatcgccgc ctgccttgcc cgctgctgga 3540 caggggctcg gctgttgggc actgacaatt ccgtggtgtt gtcggggaaa tcatcgtcct 3600 ttccttggct gctcgcctgt gttgccacct ggattctgcg cgggacgtcc ttctgctacg 3660 tcccttcggc cctcaatcca gcggaccttc cttcccgcgg cctgctgccg gctctgcggc 3720 ctcttccgcg tcttcgcctt cgccctcaga cgagtcggat ctccctttgg gccgcctccc 3780 cgcactgccc gggtggcatc cctgtgaccc ctccccagtg cctctcctgg ccctggaagt 3840 tgccactcca gtgcccacca gccttgtcct aataaaatta agttgcatca ttttgtctga 3900 ctaggtgtcc ttctataata ttatggggtg gaggggggtg gtatggagca aggggcccaa 3960 gttgggaaga aacctgtagg gcctgc 3986 <210> SEQ ID NO 12 <211> LENGTH: 4417 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Made in Labe - full polynucleotide sequence of vector genome <400> SEQUENCE: 12 gcgcgctcgc tcgctcactg aggccgcccg ggcaaagccc gggcgtcggg cgacctttgg 60 tcgcccggcc tcagtgagcg agcgagcgcg cagagaggga gtggccaact ccatcactag 120 gggttccttg tagttaatga ttaacccgcc atgctactta tctacgtaac ccttcagatt 180 aaaaataact gaggtaaggg cctgggtagg ggaggtggtg tgagacgctc ctgtctctcc 240 tctatctgcc catcggccct ttggggagga ggaatgtgcc caaggactaa aaaaaggcca 300 tggagccaga ggggcgaggg caacagacct ttcatgggca aaccttgggg ccctgctgtc 360 tagcatgccc cactacgggt ctaggctgcc catgtaagga ggcaaggcct ggggacaccc 420 gagatgcctg gttataatta acccagacat gtggctgccc cccccccccc aacacctgct 480 gcctctaaaa ataaccctgt ccctggtgga tcccctgcat gcgaagatct tcgaacaagg 540 ctgtggggga ctgagggcag gctgtaacag gcttgggggc cagggcttat acgtgcctgg 600 gactcccaaa gtattactgt tccatgttcc cggcgaaggg ccagctgtcc cccgccagct 660 agactcagca cttagtttag gaaccagtga gcaagtcagc ccttggggca gcccatacaa 720 ggccatgggg ctgggcaagc tgcacgcctg ggtccggggt gggcacggtg cccgggcaac 780 gagctgaaag ctcatctgct ctcaggggcc cctccctggg gacagcccct cctggctagt 840 cacaccctgt aggctcctct atataaccca ggggcacagg ggctgccctc attctaccac 900 cacctccaca gcacagacag acactcagga gccagccagg ccaccatggc agcccccggc 960 gccccagctg agtacggcta catccggacc gtcctgggcc agcagatcct gggacaactg 1020 gacagctcca gcctggcgct gccctccgag gccaagctga agctggcggg gagcagcggc 1080 cgcggcggcc agacagtcaa gagcctgcgg atccaggagc aggtgcagca gaccctcgcc 1140 cggaagggcc gcagctccgt gggcaacgga aatcttcacc gaaccagcag tgttcctgag 1200 tatgtctaca acctacactt ggttgaaaat gattttgttg gaggccgttc ccctgttcct 1260 aaaacctatg acatgctaaa ggctggcaca actgccactt atgaaggtcg ctggggaaga 1320 ggaacagcac agtacagctc ccagaagtcc gtggaagaaa ggtccttgag gcatcctctg 1380 aggagactgg agatttctcc tgacagcagc ccggagaggg ctcactacac gcacagcgat 1440 taccagtaca gccagagaag ccaggctggg cacaccctgc accaccaaga aagcaggcgg 1500 gccgccctcc tagtgccacc gagatatgct cgttccgaga tcgtgggggt cagccgtgct 1560 ggcaccacaa gcaggcagcg ccactttgac acataccaca gacagtacca gcatggctct 1620 gttagcgaca ccgtttttga cagcatccct gccaacccgg ccctgctcac gtaccccagg 1680 ccagggacca gccgcagcat gggcaacctc ttggagaagg agaactacct gacggcaggg 1740 ctcactgtcg ggcaggtcag gccgctggtg cccctgcagc ccgtcactca gaacagggct 1800 tccaggtcct cctggcatca gagctccttc cacagcaccc gcacgctgag ggaagctggg 1860 cccagtgtcg ccgtggattc cagcgggagg agagcgcact tgactgtcgg ccaggcggcc 1920 gcagggggaa gtgggaatct gctcactgag agaagcactt tcactgactc ccagctgggg 1980 aatgcagaca tggagatgac tctggagcga gcagtgagta tgctcgaggc agaccacatg 2040 ctgccatcca ggatttctgc tgcagctact ttcatacagc acgagtgctt ccagaaatct 2100 gaagctcgga agagggttaa ccagcttcgt ggcatcctca agcttctgca gctcctaaaa 2160 gttcagaatg aagacgttca gcgagctgtg tgtggggcct tgagaaactt agtatttgaa 2220 gacaatgaca acaaattgga ggtggctgaa ctaaatgggg tacctcggct gctccaggtg 2280 ctgaagcaaa ccagagactt ggagactaaa aaacaaataa caggtttgct gtggaatttg 2340 tcatctaatg acaaactcaa gaatctcatg ataacagaag cattgcttac gctgacggag 2400 aatatcatca tccccttttc tgggtggcct gaaggagact acccaaaagc aaatggtttg 2460 ctcgattttg acatattcta caacgtcact ggatgcctaa gaaacatgag ttctgctggc 2520 gctgatggga gaaaagcgat gagaagatgt gacggactca ttgactcact ggtccattat 2580 gtcagaggaa ccattgcaga ttaccagcca gatgacaagg ccacggagaa ttgtgtgtgc 2640 attcttcata acctctccta ccagctggag gcagagctcc cagagaaata ttcccagaat 2700 atctatattc aaaaccggaa tatccagact gacaacaaca aaagtattgg atgttttggc 2760 agtcgaagca ggaaagtaaa agagcaatac caggacgtgc cgatgccgga ggaaaagagc 2820 aaccccaagg gcgtggagtg gctgtggcat tccattgtta taaggatgta tctgtccttg 2880 atcgccaaaa gtgtccgcaa ctacacacaa gaagcatcct taggagctct gcagaacctc 2940 acggccggaa gtggaccaat gccgacatca gtggctcaga cagttgtcca gaaggaaagt 3000 ggcctgcagc acacccgaaa gatgctgcat gttggtgacc caagtgtgaa aaagacagcc 3060 atctcgctgc tgaggaatct gtcccggaat ctttctctgc agaatgaaat tgccaaagaa 3120 actctccctg atttggtttc catcattcct gacacagtcc cgagtactga ccttctcatt 3180 gaaactacag cctctgcctg ttacacattg aacaacataa tccaaaacag ttaccagaat 3240 gcacgcgacc ttctaaacac cgggggcatc cagaaaatta tggccattag tgcaggcgat 3300 gcctatgcct ccaacaaagc aagtaaagct gcttccgtcc ttctgtattc tctgtgggca 3360 cacacggaac tgcatcatgc ctacaagaag gctcagttta agaagacaga ttttgtcaac 3420 agccggactg ccaaagccta ccactccctt aaagactgat caacctctgg attacaaaat 3480 ttgtgaaaga ttgactggta ttcttaacta tgttgctcct tttacgctat gtggatacgc 3540 tgctttaatg cctttgtatc atgctattgc ttcccgtatg gctttcattt tctcctcctt 3600 gtataaatcc tggttgctgt ctctttatga ggagttgtgg cccgttgtca ggcaacgtgg 3660 cgtggtgtgc actgtgtttg ctgacgcaac ccccactggt tggggcattg ccaccacctg 3720 tcagctcctt tccgggactt tcgctttccc cctccctatt gccacggcgg aactcatcgc 3780 cgcctgcctt gcccgctgct ggacaggggc tcggctgttg ggcactgaca attccgtggt 3840 gttgtcgggg aaatcatcgt cctttccttg gctgctcgcc tgtgttgcca cctggattct 3900 gcgcgggacg tccttctgct acgtcccttc ggccctcaat ccagcggacc ttccttcccg 3960 cggcctgctg ccggctctgc ggcctcttcc gcgtcttcgc cttcgccctc agacgagtcg 4020 gatctccctt tgggccgcct ccccgcactg cccgggtggc atccctgtga cccctcccca 4080 gtgcctctcc tggccctgga agttgccact ccagtgccca ccagccttgt cctaataaaa 4140 ttaagttgca tcattttgtc tgactaggtg tccttctata atattatggg gtggaggggg 4200 gtggtatgga gcaaggggcc caagttggga agaaacctgt agggcctgct acgtagataa 4260 gtagcatggc gggttaatca ttaactacaa ggaaccccta gtgatggagt tggccactcc 4320 ctctctgcgc gctcgctcgc tcactgaggc cgggcgacca aaggtcgccc gacgcccggg 4380 ctttgcccgg gcggcctcag tgagcgagcg agcgcgc 4417 <210> SEQ ID NO 13 <211> LENGTH: 4190 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Made in Labe - full polynucleotide sequence of vector genome <400> SEQUENCE: 13 gcgcgctcgc tcgctcactg aggccgcccg ggcaaagccc gggcgtcggg cgacctttgg 60 tcgcccggcc tcagtgagcg agcgagcgcg cagagaggga gtggccaact ccatcactag 120 gggttccttg tagttaatga ttaacccgcc atgctactta tctacgtact cagtccatta 180 ggagccagta gcctggaaga tgtctttacc cccagcatca gttcaagtgg agcagcacat 240 aactcttgcc ctctgccttc caagattctg gtgctgagac ttatggagtg tcttggaggt 300 tgccttctgc cccccaaccc tgctcccagc tggccctccc aggcctgggt tgctggcctc 360 tgctttatca ggattctcaa gagggacagc tggtttatgt tgcatgactg ttccctgcat 420 atctgctctg gttttaaata gcttatctga gcagctggag gaccacatgg gcttatatgg 480 cgtggggtac atgttcctgt agccttgtcc ctggcacctg ccaaaatagc agccaacacc 540 ccccaccccc accgccatcc ccctgcccca cccgtcccct gtcgcacatt cctccctccg 600 cagggctggc tcaccaggcc ccagcccaca tgcctgctta aagccctctc catcctctgc 660 ctcacccagt ccccgctgag actgagcaga cgcctccagg atctgtcggc aggccaccat 720 ggcagccccc ggcgccccag ctgagtacgg ctacatccgg accgtcctgg gccagcagat 780 cctgggacaa ctggacagct ccagcctggc gctgccctcc gaggccaagc tgaagctggc 840 ggggagcagc ggccgcggcg gccagacagt caagagcctg cggatccagg agcaggtgca 900 gcagaccctc gcccggaagg gccgcagctc cgtgggcaac ggaaatcttc accgaaccag 960 cagtgttcct gagtatgtct acaacctaca cttggttgaa aatgattttg ttggaggccg 1020 ttcccctgtt cctaaaacct atgacatgct aaaggctggc acaactgcca cttatgaagg 1080 tcgctgggga agaggaacag cacagtacag ctcccagaag tccgtggaag aaaggtcctt 1140 gaggcatcct ctgaggagac tggagatttc tcctgacagc agcccggaga gggctcacta 1200 cacgcacagc gattaccagt acagccagag aagccaggct gggcacaccc tgcaccacca 1260 agaaagcagg cgggccgccc tcctagtgcc accgagatat gctcgttccg agatcgtggg 1320 ggtcagccgt gctggcacca caagcaggca gcgccacttt gacacatacc acagacagta 1380 ccagcatggc tctgttagcg acaccgtttt tgacagcatc cctgccaacc cggccctgct 1440 cacgtacccc aggccaggga ccagccgcag catgggcaac ctcttggaga aggagaacta 1500 cctgacggca gggctcactg tcgggcaggt caggccgctg gtgcccctgc agcccgtcac 1560 tcagaacagg gcttccaggt cctcctggca tcagagctcc ttccacagca cccgcacgct 1620 gagggaagct gggcccagtg tcgccgtgga ttccagcggg aggagagcgc acttgactgt 1680 cggccaggcg gccgcagggg gaagtgggaa tctgctcact gagagaagca ctttcactga 1740 ctcccagctg gggaatgcag acatggagat gactctggag cgagcagtga gtatgctcga 1800 ggcagaccac atgctgccat ccaggatttc tgctgcagct actttcatac agcacgagtg 1860 cttccagaaa tctgaagctc ggaagagggt taaccagctt cgtggcatcc tcaagcttct 1920 gcagctccta aaagttcaga atgaagacgt tcagcgagct gtgtgtgggg ccttgagaaa 1980 cttagtattt gaagacaatg acaacaaatt ggaggtggct gaactaaatg gggtacctcg 2040 gctgctccag gtgctgaagc aaaccagaga cttggagact aaaaaacaaa taacaggttt 2100 gctgtggaat ttgtcatcta atgacaaact caagaatctc atgataacag aagcattgct 2160 tacgctgacg gagaatatca tcatcccctt ttctgggtgg cctgaaggag actacccaaa 2220 agcaaatggt ttgctcgatt ttgacatatt ctacaacgtc actggatgcc taagaaacat 2280 gagttctgct ggcgctgatg ggagaaaagc gatgagaaga tgtgacggac tcattgactc 2340 actggtccat tatgtcagag gaaccattgc agattaccag ccagatgaca aggccacgga 2400 gaattgtgtg tgcattcttc ataacctctc ctaccagctg gaggcagagc tcccagagaa 2460 atattcccag aatatctata ttcaaaaccg gaatatccag actgacaaca acaaaagtat 2520 tggatgtttt ggcagtcgaa gcaggaaagt aaaagagcaa taccaggacg tgccgatgcc 2580 ggaggaaaag agcaacccca agggcgtgga gtggctgtgg cattccattg ttataaggat 2640 gtatctgtcc ttgatcgcca aaagtgtccg caactacaca caagaagcat ccttaggagc 2700 tctgcagaac ctcacggccg gaagtggacc aatgccgaca tcagtggctc agacagttgt 2760 ccagaaggaa agtggcctgc agcacacccg aaagatgctg catgttggtg acccaagtgt 2820 gaaaaagaca gccatctcgc tgctgaggaa tctgtcccgg aatctttctc tgcagaatga 2880 aattgccaaa gaaactctcc ctgatttggt ttccatcatt cctgacacag tcccgagtac 2940 tgaccttctc attgaaacta cagcctctgc ctgttacaca ttgaacaaca taatccaaaa 3000 cagttaccag aatgcacgcg accttctaaa caccgggggc atccagaaaa ttatggccat 3060 tagtgcaggc gatgcctatg cctccaacaa agcaagtaaa gctgcttccg tccttctgta 3120 ttctctgtgg gcacacacgg aactgcatca tgcctacaag aaggctcagt ttaagaagac 3180 agattttgtc aacagccgga ctgccaaagc ctaccactcc cttaaagact gatcaacctc 3240 tggattacaa aatttgtgaa agattgactg gtattcttaa ctatgttgct ccttttacgc 3300 tatgtggata cgctgcttta atgcctttgt atcatgctat tgcttcccgt atggctttca 3360 ttttctcctc cttgtataaa tcctggttgc tgtctcttta tgaggagttg tggcccgttg 3420 tcaggcaacg tggcgtggtg tgcactgtgt ttgctgacgc aacccccact ggttggggca 3480 ttgccaccac ctgtcagctc ctttccggga ctttcgcttt ccccctccct attgccacgg 3540 cggaactcat cgccgcctgc cttgcccgct gctggacagg ggctcggctg ttgggcactg 3600 acaattccgt ggtgttgtcg gggaaatcat cgtcctttcc ttggctgctc gcctgtgttg 3660 ccacctggat tctgcgcggg acgtccttct gctacgtccc ttcggccctc aatccagcgg 3720 accttccttc ccgcggcctg ctgccggctc tgcggcctct tccgcgtctt cgccttcgcc 3780 ctcagacgag tcggatctcc ctttgggccg cctccccgca ctgcccgggt ggcatccctg 3840 tgacccctcc ccagtgcctc tcctggccct ggaagttgcc actccagtgc ccaccagcct 3900 tgtcctaata aaattaagtt gcatcatttt gtctgactag gtgtccttct ataatattat 3960 ggggtggagg ggggtggtat ggagcaaggg gcccaagttg ggaagaaacc tgtagggcct 4020 gctacgtaga taagtagcat ggcgggttaa tcattaacta caaggaaccc ctagtgatgg 4080 agttggccac tccctctctg cgcgctcgct cgctcactga ggccgggcga ccaaaggtcg 4140 cccgacgccc gggctttgcc cgggcggcct cagtgagcga gcgagcgcgc 4190 <210> SEQ ID NO 14 <211> LENGTH: 4549 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Made in Labe - full polynucleotide sequence of vector genome <400> SEQUENCE: 14 gcgcgctcgc tcgctcactg aggccgcccg ggcaaagccc gggcgtcggg cgacctttgg 60 tcgcccggcc tcagtgagcg agcgagcgcg cagagaggga gtggccaact ccatcactag 120 gggttccttg tagttaatga ttaacccgcc atgctactta tctacgtaac ccttcagatt 180 aaaaataact gaggtaaggg cctgggtagg ggaggtggtg tgagacgctc ctgtctctcc 240 tctatctgcc catcggccct ttggggagga ggaatgtgcc caaggactaa aaaaaggcca 300 tggagccaga ggggcgaggg caacagacct ttcatgggca aaccttgggg ccctgctgtc 360 tagcatgccc cactacgggt ctaggctgcc catgtaagga ggcaaggcct ggggacaccc 420 gagatgcctg gttataatta acccagacat gtggctgccc cccccccccc aacacctgct 480 gcctctaaaa ataaccctgt ccctggtgga tcccctgcat gcgaagatct tcgaacaagg 540 ctgtggggga ctgagggcag gctgtaacag gcttgggggc cagggcttat acgtgcctgg 600 gactcccaaa gtattactgt tccatgttcc cggcgaaggg ccagctgtcc cccgccagct 660 agactcagca cttagtttag gaaccagtga gcaagtcagc ccttggggca gcccatacaa 720 ggccatgggg ctgggcaagc tgcacgcctg ggtccggggt gggcacggtg cccgggcaac 780 gagctgaaag ctcatctgct ctcaggggcc cctccctggg gacagcccct cctggctagt 840 cacaccctgt aggctcctct atataaccca ggggcacagg ggctgccctc attctaccac 900 cacctccaca gcacagacag acactcagga gccagccagg ccaccatggc agcccccggc 960 gccccagctg agtacggcta catccggacc gtcctgggcc agcagatcct gggacaactg 1020 gacagctcca gcctggcgct gccctccgag gccaagctga agctggcggg gagcagcggc 1080 cgcggcggcc agacagtcaa gagcctgcgg atccaggagc aggtgcagca gaccctcgcc 1140 cggaagggcc gcagctccgt gggcaacgga aatcttcacc gaaccagcag tgttcctgag 1200 tatgtctaca acctacactt ggttgaaaat gattttgttg gaggccgttc ccctgttcct 1260 aaaacctatg acatgctaaa ggctggcaca actgccactt atgaaggtcg ctggggaaga 1320 ggaacagcac agtacagctc ccagaagtcc gtggaagaaa ggtccttgag gcatcctctg 1380 aggagactgg agatttctcc tgacagcagc ccggagaggg ctcactacac gcacagcgat 1440 taccagtaca gccagagaag ccaggctggg cacaccctgc accaccaaga aagcaggcgg 1500 gccgccctcc tagtgccacc gagatatgct cgttccgaga tcgtgggggt cagccgtgct 1560 ggcaccacaa gcaggcagcg ccactttgac acataccaca gacagtacca gcatggctct 1620 gttagcgaca ccgtttttga cagcatccct gccaacccgg ccctgctcac gtaccccagg 1680 ccagggacca gccgcagcat gggcaacctc ttggagaagg agaactacct gacggcaggg 1740 ctcactgtcg ggcaggtcag gccgctggtg cccctgcagc ccgtcactca gaacagggct 1800 tccaggtcct cctggcatca gagctccttc cacagcaccc gcacgctgag ggaagctggg 1860 cccagtgtcg ccgtggattc cagcgggagg agagcgcact tgactgtcgg ccaggcggcc 1920 gcagggggaa gtgggaatct gctcactgag agaagcactt tcactgactc ccagctgggg 1980 aatgcagaca tggagatgac tctggagcga gcagtgagta tgctcgaggc agaccacatg 2040 ctgccatcca ggatttctgc tgcagctact ttcatacagc acgagtgctt ccagaaatct 2100 gaagctcgga agagggttaa ccagcttcgt ggcatcctca agcttctgca gctcctaaaa 2160 gttcagaatg aagacgttca gcgagctgtg tgtggggcct tgagaaactt agtatttgaa 2220 gacaatgaca acaaattgga ggtggctgaa ctaaatgggg tacctcggct gctccaggtg 2280 ctgaagcaaa ccagagactt ggagactaaa aaacaaataa cagaccatac agtcaattta 2340 agaagtagga atggctggcc gggcgcggtg gctcacgcct gtaatcccag cactttggga 2400 ggccaaggcg ggcggatcac gaggtcagga gttcgagacc agcctgacca acatggtttg 2460 ctgtggaatt tgtcatctaa tgacaaactc aagaatctca tgataacaga agcattgctt 2520 acgctgacgg agaatatcat catccccttt tctgggtggc ctgaaggaga ctacccaaaa 2580 gcaaatggtt tgctcgattt tgacatattc tacaacgtca ctggatgcct aagaaacatg 2640 agttctgctg gcgctgatgg gagaaaagcg atgagaagat gtgacggact cattgactca 2700 ctggtccatt atgtcagagg aaccattgca gattaccagc cagatgacaa ggccacggag 2760 aattgtgtgt gcattcttca taacctctcc taccagctgg aggcagagct cccagagaaa 2820 tattcccaga atatctatat tcaaaaccgg aatatccaga ctgacaacaa caaaagtatt 2880 ggatgttttg gcagtcgaag caggaaagta aaagagcaat accaggacgt gccgatgccg 2940 gaggaaaaga gcaaccccaa gggcgtggag tggctgtggc attccattgt tataaggatg 3000 tatctgtcct tgatcgccaa aagtgtccgc aactacacac aagaagcatc cttaggagct 3060 ctgcagaacc tcacggccgg aagtggacca atgccgacat cagtggctca gacagttgtc 3120 cagaaggaaa gtggcctgca gcacacccga aagatgctgc atgttggtga cccaagtgtg 3180 aaaaagacag ccatctcgct gctgaggaat ctgtcccgga atctttctct gcagaatgaa 3240 attgccaaag aaactctccc tgatttggtt tccatcattc ctgacacagt cccgagtact 3300 gaccttctca ttgaaactac agcctctgcc tgttacacat tgaacaacat aatccaaaac 3360 agttaccaga atgcacgcga ccttctaaac accgggggca tccagaaaat tatggccatt 3420 agtgcaggcg atgcctatgc ctccaacaaa gcaagtaaag ctgcttccgt ccttctgtat 3480 tctctgtggg cacacacgga actgcatcat gcctacaaga aggctcagtt taagaagaca 3540 gattttgtca acagccggac tgccaaagcc taccactccc ttaaagactg atcaacctct 3600 ggattacaaa atttgtgaaa gattgactgg tattcttaac tatgttgctc cttttacgct 3660 atgtggatac gctgctttaa tgcctttgta tcatgctatt gcttcccgta tggctttcat 3720 tttctcctcc ttgtataaat cctggttgct gtctctttat gaggagttgt ggcccgttgt 3780 caggcaacgt ggcgtggtgt gcactgtgtt tgctgacgca acccccactg gttggggcat 3840 tgccaccacc tgtcagctcc tttccgggac tttcgctttc cccctcccta ttgccacggc 3900 ggaactcatc gccgcctgcc ttgcccgctg ctggacaggg gctcggctgt tgggcactga 3960 caattccgtg gtgttgtcgg ggaaatcatc gtcctttcct tggctgctcg cctgtgttgc 4020 cacctggatt ctgcgcggga cgtccttctg ctacgtccct tcggccctca atccagcgga 4080 ccttccttcc cgcggcctgc tgccggctct gcggcctctt ccgcgtcttc gccttcgccc 4140 tcagacgagt cggatctccc tttgggccgc ctccccgcac tgcccgggtg gcatccctgt 4200 gacccctccc cagtgcctct cctggccctg gaagttgcca ctccagtgcc caccagcctt 4260 gtcctaataa aattaagttg catcattttg tctgactagg tgtccttcta taatattatg 4320 gggtggaggg gggtggtatg gagcaagggg cccaagttgg gaagaaacct gtagggcctg 4380 ctacgtagat aagtagcatg gcgggttaat cattaactac aaggaacccc tagtgatgga 4440 gttggccact ccctctctgc gcgctcgctc gctcactgag gccgggcgac caaaggtcgc 4500 ccgacgcccg ggctttgccc gggcggcctc agtgagcgag cgagcgcgc 4549 <210> SEQ ID NO 15 <211> LENGTH: 4322 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Made in Labe - full polynucleotide sequence of vector genome <400> SEQUENCE: 15 gcgcgctcgc tcgctcactg aggccgcccg ggcaaagccc gggcgtcggg cgacctttgg 60 tcgcccggcc tcagtgagcg agcgagcgcg cagagaggga gtggccaact ccatcactag 120 gggttccttg tagttaatga ttaacccgcc atgctactta tctacgtact cagtccatta 180 ggagccagta gcctggaaga tgtctttacc cccagcatca gttcaagtgg agcagcacat 240 aactcttgcc ctctgccttc caagattctg gtgctgagac ttatggagtg tcttggaggt 300 tgccttctgc cccccaaccc tgctcccagc tggccctccc aggcctgggt tgctggcctc 360 tgctttatca ggattctcaa gagggacagc tggtttatgt tgcatgactg ttccctgcat 420 atctgctctg gttttaaata gcttatctga gcagctggag gaccacatgg gcttatatgg 480 cgtggggtac atgttcctgt agccttgtcc ctggcacctg ccaaaatagc agccaacacc 540 ccccaccccc accgccatcc ccctgcccca cccgtcccct gtcgcacatt cctccctccg 600 cagggctggc tcaccaggcc ccagcccaca tgcctgctta aagccctctc catcctctgc 660 ctcacccagt ccccgctgag actgagcaga cgcctccagg atctgtcggc aggccaccat 720 ggcagccccc ggcgccccag ctgagtacgg ctacatccgg accgtcctgg gccagcagat 780 cctgggacaa ctggacagct ccagcctggc gctgccctcc gaggccaagc tgaagctggc 840 ggggagcagc ggccgcggcg gccagacagt caagagcctg cggatccagg agcaggtgca 900 gcagaccctc gcccggaagg gccgcagctc cgtgggcaac ggaaatcttc accgaaccag 960 cagtgttcct gagtatgtct acaacctaca cttggttgaa aatgattttg ttggaggccg 1020 ttcccctgtt cctaaaacct atgacatgct aaaggctggc acaactgcca cttatgaagg 1080 tcgctgggga agaggaacag cacagtacag ctcccagaag tccgtggaag aaaggtcctt 1140 gaggcatcct ctgaggagac tggagatttc tcctgacagc agcccggaga gggctcacta 1200 cacgcacagc gattaccagt acagccagag aagccaggct gggcacaccc tgcaccacca 1260 agaaagcagg cgggccgccc tcctagtgcc accgagatat gctcgttccg agatcgtggg 1320 ggtcagccgt gctggcacca caagcaggca gcgccacttt gacacatacc acagacagta 1380 ccagcatggc tctgttagcg acaccgtttt tgacagcatc cctgccaacc cggccctgct 1440 cacgtacccc aggccaggga ccagccgcag catgggcaac ctcttggaga aggagaacta 1500 cctgacggca gggctcactg tcgggcaggt caggccgctg gtgcccctgc agcccgtcac 1560 tcagaacagg gcttccaggt cctcctggca tcagagctcc ttccacagca cccgcacgct 1620 gagggaagct gggcccagtg tcgccgtgga ttccagcggg aggagagcgc acttgactgt 1680 cggccaggcg gccgcagggg gaagtgggaa tctgctcact gagagaagca ctttcactga 1740 ctcccagctg gggaatgcag acatggagat gactctggag cgagcagtga gtatgctcga 1800 ggcagaccac atgctgccat ccaggatttc tgctgcagct actttcatac agcacgagtg 1860 cttccagaaa tctgaagctc ggaagagggt taaccagctt cgtggcatcc tcaagcttct 1920 gcagctccta aaagttcaga atgaagacgt tcagcgagct gtgtgtgggg ccttgagaaa 1980 cttagtattt gaagacaatg acaacaaatt ggaggtggct gaactaaatg gggtacctcg 2040 gctgctccag gtgctgaagc aaaccagaga cttggagact aaaaaacaaa taacagacca 2100 tacagtcaat ttaagaagta ggaatggctg gccgggcgcg gtggctcacg cctgtaatcc 2160 cagcactttg ggaggccaag gcgggcggat cacgaggtca ggagttcgag accagcctga 2220 ccaacatggt ttgctgtgga atttgtcatc taatgacaaa ctcaagaatc tcatgataac 2280 agaagcattg cttacgctga cggagaatat catcatcccc ttttctgggt ggcctgaagg 2340 agactaccca aaagcaaatg gtttgctcga ttttgacata ttctacaacg tcactggatg 2400 cctaagaaac atgagttctg ctggcgctga tgggagaaaa gcgatgagaa gatgtgacgg 2460 actcattgac tcactggtcc attatgtcag aggaaccatt gcagattacc agccagatga 2520 caaggccacg gagaattgtg tgtgcattct tcataacctc tcctaccagc tggaggcaga 2580 gctcccagag aaatattccc agaatatcta tattcaaaac cggaatatcc agactgacaa 2640 caacaaaagt attggatgtt ttggcagtcg aagcaggaaa gtaaaagagc aataccagga 2700 cgtgccgatg ccggaggaaa agagcaaccc caagggcgtg gagtggctgt ggcattccat 2760 tgttataagg atgtatctgt ccttgatcgc caaaagtgtc cgcaactaca cacaagaagc 2820 atccttagga gctctgcaga acctcacggc cggaagtgga ccaatgccga catcagtggc 2880 tcagacagtt gtccagaagg aaagtggcct gcagcacacc cgaaagatgc tgcatgttgg 2940 tgacccaagt gtgaaaaaga cagccatctc gctgctgagg aatctgtccc ggaatctttc 3000 tctgcagaat gaaattgcca aagaaactct ccctgatttg gtttccatca ttcctgacac 3060 agtcccgagt actgaccttc tcattgaaac tacagcctct gcctgttaca cattgaacaa 3120 cataatccaa aacagttacc agaatgcacg cgaccttcta aacaccgggg gcatccagaa 3180 aattatggcc attagtgcag gcgatgccta tgcctccaac aaagcaagta aagctgcttc 3240 cgtccttctg tattctctgt gggcacacac ggaactgcat catgcctaca agaaggctca 3300 gtttaagaag acagattttg tcaacagccg gactgccaaa gcctaccact cccttaaaga 3360 ctgatcaacc tctggattac aaaatttgtg aaagattgac tggtattctt aactatgttg 3420 ctccttttac gctatgtgga tacgctgctt taatgccttt gtatcatgct attgcttccc 3480 gtatggcttt cattttctcc tccttgtata aatcctggtt gctgtctctt tatgaggagt 3540 tgtggcccgt tgtcaggcaa cgtggcgtgg tgtgcactgt gtttgctgac gcaaccccca 3600 ctggttgggg cattgccacc acctgtcagc tcctttccgg gactttcgct ttccccctcc 3660 ctattgccac ggcggaactc atcgccgcct gccttgcccg ctgctggaca ggggctcggc 3720 tgttgggcac tgacaattcc gtggtgttgt cggggaaatc atcgtccttt ccttggctgc 3780 tcgcctgtgt tgccacctgg attctgcgcg ggacgtcctt ctgctacgtc ccttcggccc 3840 tcaatccagc ggaccttcct tcccgcggcc tgctgccggc tctgcggcct cttccgcgtc 3900 ttcgccttcg ccctcagacg agtcggatct ccctttgggc cgcctccccg cactgcccgg 3960 gtggcatccc tgtgacccct ccccagtgcc tctcctggcc ctggaagttg ccactccagt 4020 gcccaccagc cttgtcctaa taaaattaag ttgcatcatt ttgtctgact aggtgtcctt 4080 ctataatatt atggggtgga ggggggtggt atggagcaag gggcccaagt tgggaagaaa 4140 cctgtagggc ctgctacgta gataagtagc atggcgggtt aatcattaac tacaaggaac 4200 ccctagtgat ggagttggcc actccctctc tgcgcgctcg ctcgctcact gaggccgggc 4260 gaccaaaggt cgcccgacgc ccgggctttg cccgggcggc ctcagtgagc gagcgagcgc 4320 gc 4322 <210> SEQ ID NO 16 <211> LENGTH: 13 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Kozak sequence motif <400> SEQUENCE: 16 gccgccrcca ugg 13 <210> SEQ ID NO 17 <400> SEQUENCE: 17 000 <210> SEQ ID NO 18 <211> LENGTH: 10 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Kozak sequence motif <400> SEQUENCE: 18 gacaccaugg 10 <210> SEQ ID NO 19 <400> SEQUENCE: 19 000 <210> SEQ ID NO 20 <211> LENGTH: 141 <212> TYPE: DNA <213> ORGANISM: Adeno-associated virus <400> SEQUENCE: 20 cctgcaggca gctgcgcgct cgctcgctca ctgaggccgc ccgggcaaag cccgggcgtc 60 gggcgacctt tggtcgcccg gcctcagtga gcgagcgagc gcgcagagag ggagtggcca 120 actccatcac taggggttcc t 141 <210> SEQ ID NO 21 <211> LENGTH: 168 <212> TYPE: DNA <213> ORGANISM: Adeno-associated virus 2 <400> SEQUENCE: 21 gcgcgctcgc tcgctcactg aggccgcccg ggcaaagccc gggcgtcggg cgacctttgg 60 tcgcccggcc tcagtgagcg agcgagcgcg cagagaggga gtggccaact ccatcactag 120 gggttccttg tagttaatga ttaacccgcc atgctactta tctacgta 168 <210> SEQ ID NO 22 <211> LENGTH: 170 <212> TYPE: DNA <213> ORGANISM: Adeno-associated virus <400> SEQUENCE: 22 ctgcgcgctc gctcgctcac tgaggccgcc cgggcaaagc ccgggcgtcg ggcgaccttt 60 ggtcgcccgg cctcagtgag cgagcgagcg cgcagagagg gagtggccaa ctccatcact 120 aggggttcct tgtagttaat gattaacccg ccatgctact tatctacgta 170 <210> SEQ ID NO 23 <211> LENGTH: 145 <212> TYPE: DNA <213> ORGANISM: Adeno-associated virus <400> SEQUENCE: 23 ttggccactc cctctctgcg cgctcgctcg ctcactgagg ccgcccgggc aaagcccggg 60 cgtcgggcga cctttggtcg cccggcctca gtgagcgagc gagcgcgcag agagggagtg 120 gccaactcca tcactagggg ttcct 145 <210> SEQ ID NO 24 <211> LENGTH: 141 <212> TYPE: DNA <213> ORGANISM: Adeno-associated viurs <400> SEQUENCE: 24 aggaacccct agtgatggag ttggccactc cctctctgcg cgctcgctcg ctcactgagg 60 ccgggcgacc aaaggtcgcc cgacgcccgg gctttgcccg ggcggcctca gtgagcgagc 120 gagcgcgcag ctgcctgcag g 141 <210> SEQ ID NO 25 <211> LENGTH: 168 <212> TYPE: DNA <213> ORGANISM: Adeno-associated virus 2 <400> SEQUENCE: 25 tacgtagata agtagcatgg cgggttaatc attaactaca aggaacccct agtgatggag 60 ttggccactc cctctctgcg cgctcgctcg ctcactgagg ccgggcgacc aaaggtcgcc 120 cgacgcccgg gctttgcccg ggcggcctca gtgagcgagc gagcgcgc 168 <210> SEQ ID NO 26 <211> LENGTH: 133 <212> TYPE: DNA <213> ORGANISM: Adeno-associated virus 2 <400> SEQUENCE: 26 aggaacccct agtgatggag actccctctc tgcgcgctcg ctcgctcact gaggccgggc 60 gaccaaaggt cgcccgacgc ccgggctttg cccgggcggc ctcagtgagc gagcgagcgc 120 gcagagaggg agt 133 <210> SEQ ID NO 27 <211> LENGTH: 124 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Made in Lab - vector filler sequence <400> SEQUENCE: 27 gcggcaattc agtcgataac tataacggtc ctaaggtagc gatttaaata cgcgctctct 60 taaggtagcc ccgggacgcg tcaattgact acaaaccgag tatctgcaga gggccctgcg 120 tatg 124 <210> SEQ ID NO 28 <211> LENGTH: 84 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Made in Lab - vector filler sequence <400> SEQUENCE: 28 cttctgaggc ggaaagaacc agatcctctc ttaaggtagc atcgagattt aaattaggga 60 taacagggta atggcgcggg ccgc 84 <210> SEQ ID NO 29 <211> LENGTH: 63 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Made in Lab - vector filler sequence <400> SEQUENCE: 29 gttacccagg ctggagtgca gtggcacatt tctgctcact gcaacctcct cctccctggg 60 ttc 63 <210> SEQ ID NO 30 <211> LENGTH: 573 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Made in lab - CAG promoter in part Human betaherpesvirus 5 <400> SEQUENCE: 30 acttacggta aatggcccgc ctggctgacc gcccaacgac ccccgcccat tgacgtcaat 60 aatgacgtat gttcccatag taacgccaat agggactttc cattgacgtc aatgggtgga 120 gtatttacgg taaactgccc acttggcagt acatcaagtg tatcatatgc caagtacgcc 180 ccctattgac gtcaatgacg gtaaatggcc cgcctggcat tatgcccagt acatgacctt 240 atgggacttt cctacttggc agtacatcta cgtattagtc atcgctatta ccatggtcga 300 ggtgagcccc acgttctgct tcactctccc catctccccc ccctccccac ccccaatttt 360 gtatttattt attttttaat tattttgtgc agcgatgggg gcgggggggg ggggggcgcg 420 cgccaggcgg ggcggggcgg ggcgaggggc ggggcggggc gaggcggaga ggtgcggcgg 480 cagccaatca gagcggcgcg ctccgaaagt ttccttttat ggcgaggcgg cggcggcggc 540 ggccctataa aaagcgaagc gcgcggcggg cgg 573 <210> SEQ ID NO 31 <211> LENGTH: 771 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Made in Lab - MHCK7 promoter <400> SEQUENCE: 31 acccttcaga ttaaaaataa ctgaggtaag ggcctgggta ggggaggtgg tgtgagacgc 60 tcctgtctct cctctatctg cccatcggcc ctttggggag gaggaatgtg cccaaggact 120 aaaaaaaggc catggagcca gaggggcgag ggcaacagac ctttcatggg caaaccttgg 180 ggccctgctg tctagcatgc cccactacgg gtctaggctg cccatgtaag gaggcaaggc 240 ctggggacac ccgagatgcc tggttataat taacccagac atgtggctgc cccccccccc 300 ccaacacctg ctgcctctaa aaataaccct gtccctggtg gatcccctgc atgcgaagat 360 cttcgaacaa ggctgtgggg gactgagggc aggctgtaac aggcttgggg gccagggctt 420 atacgtgcct gggactccca aagtattact gttccatgtt cccggcgaag ggccagctgt 480 cccccgccag ctagactcag cacttagttt aggaaccagt gagcaagtca gcccttgggg 540 cagcccatac aaggccatgg ggctgggcaa gctgcacgcc tgggtccggg gtgggcacgg 600 tgcccgggca acgagctgaa agctcatctg ctctcagggg cccctccctg gggacagccc 660 ctcctggcta gtcacaccct gtaggctcct ctatataacc caggggcaca ggggctgccc 720 tcattctacc accacctcca cagcacagac agacactcag gagccagcca g 771 <210> SEQ ID NO 32 <211> LENGTH: 544 <212> TYPE: DNA <213> ORGANISM: Homo sapiens <400> SEQUENCE: 32 ctcagtccat taggagccag tagcctggaa gatgtcttta cccccagcat cagttcaagt 60 ggagcagcac ataactcttg ccctctgcct tccaagattc tggtgctgag acttatggag 120 tgtcttggag gttgccttct gccccccaac cctgctccca gctggccctc ccaggcctgg 180 gttgctggcc tctgctttat caggattctc aagagggaca gctggtttat gttgcatgac 240 tgttccctgc atatctgctc tggttttaaa tagcttatct gagcagctgg aggaccacat 300 gggcttatat ggcgtggggt acatgttcct gtagccttgt ccctggcacc tgccaaaata 360 gcagccaaca ccccccaccc ccaccgccat ccccctgccc cacccgtccc ctgtcgcaca 420 ttcctccctc cgcagggctg gctcaccagg ccccagccca catgcctgct taaagccctc 480 tccatcctct gcctcaccca gtccccgctg agactgagca gacgcctcca ggatctgtcg 540 gcag 544 <210> SEQ ID NO 33 <211> LENGTH: 502 <212> TYPE: DNA <213> ORGANISM: Homo sapiens <400> SEQUENCE: 33 ctcagtccat taggagccag tagcctggaa gatgtcttta cccccagcat cagttcaagt 60 ggagcagcac ataactcttg ccctctgcct tccaagattc tggtgctgag acttatggag 120 tgtcttggag gttgccttct gccccccaac cctgctccca gctggccctc ccaggcctgg 180 gttgctggcc tctgctttat caggattctc aagagggaca gctggtttat gttgcatgac 240 tgttccctgc atatctgctc tggttttaaa tagcttatct gagcagctgg aggaccacat 300 gggcttatat ggcgtggggt acatgttcct gtagccttgt ccctggcacc tgccaaaata 360 gcagccaaca ccccccaccc ccaccgccat ccccctgccc cacccgtccc ctgtcgcaca 420 ttcctccctc cgcagggctg gctcaccagg ccccagccca catgcctgct taaagccctc 480 tccatcctct gcctcaccca gt 502 <210> SEQ ID NO 34 <211> LENGTH: 5464 <212> TYPE: DNA <213> ORGANISM: Mus musculus <400> SEQUENCE: 34 ggtaccggat cctgcaaggt cacacaaggg tctccaccca ccaggtgccc tagtctcaat 60 ttcagtttcc atgccttgtt ctcacaatgc tggcctcccc agagctaatt tggactttgt 120 ttttatttca aaagggcctg aatgaggagt agatcttgtg ctacccagct ctaagggtgc 180 ccgtgaagcc ctcagacctg gagcctttgc aacagccctt taggtggaag cagaataaag 240 caattttcct taaagccaaa atcctgcctc tagactcttc ttctctgacc tcggtccctg 300 ggctctaggg tggggaggtg gggcttggaa gaagaaggtg gggaagtggc aaaagccgat 360 ccctagggcc ctgtgaagtt cggagccttc cctgtacagc actggctcat agatcctcct 420 ccagccaaac atagcaagaa gtgatacctc ctttgtgact tccccaggcc cagtacctgt 480 caggttgaaa caggatttag agaagcctct gaactcacct gaactctgaa gctcatccac 540 caagcaagca cctaggtgcc actgctagtt agtatcctac gctgataata tgcagagctg 600 ggccacagaa gtcctggggt gtaggaactg accagtgact tttcagtcgg caaaggtatg 660 accccctcag cagatgtagt aatgtcccct tagatcccat cccaggcagg tctctaagag 720 gacatgggat gagagatgta gtcatgtggc attccaaaca cagctatcca cagtgtccct 780 tgccccttcc acttagccag gaggacagta accttagcct atctttcttc ctccccatcc 840 tcccaggaca caccccctgg tctgcagtat tcatttcttc cttcacgtcc cctctgtgac 900 ttccatttgc aaggcttttg acctctgcag ctgctggaag atagagtttg gccctaggtg 960 tggcaagcca tctcaagaga aagcagacaa cagggggacc agattttgga aggatcagga 1020 actaaatcac tggcgggcct gggggtagaa aaaagagtga gtgagtccgc tccagctaag 1080 ccaagctagt ccccgagata ctctgccaca gctgggctgc tcggggtagc tttaggaatg 1140 tgggtctgaa agacaatggg attggaagac atctctttga gtctcccctc aaccccacct 1200 acagacacac tcgtgtgtgg ccagactcct gttcaacagc cctctgtgtt ctgaccactg 1260 agctaggcaa ccagagcatg ggccctgtgc tgaggatgaa gagttggtta ccaatagcaa 1320 aaacagcagg ggagggagaa cagagaacga aataaggaag gaagaaggaa aggccagtca 1380 atcagatgca gtcagaagag atgggaagcc aacacacagc ttgagcagag gaaacagaaa 1440 agggagagat tctgggcata aggaggccac agaaagaaga gcccaggccc cccaagtctc 1500 ctctttatac cctcatcccg tctcccaatt aagcccactc ttcttcctag atcagacctg 1560 agctgcagcg aagagacccg tagggaggat cacactggat gaaggagatg tgtggagaag 1620 tccagggaac ctaagagcca gagcctaaaa gagcaagaga taaaggtgct tcaaaggtgg 1680 ccaggctgtg cacacagagg gtcgaggact ggtggtagag cctcaagata aggatgatgc 1740 tcagaatggg cggggggggg gattctgggg gggggagaga gaaggtgaga aggagcctgg 1800 aacagagaat ctggaagcgc tggaaacgat accataaagg gaagaaccca ggctaccttt 1860 agatgtaaat catgaaagac agggagaagg gaagctggag agagtagaag gaccccgggg 1920 caagacattg aagcaaggac aagccaggtt gagcgctccg tgaaatcagc ctgctgaagg 1980 cagagccctg gtatgagcac cagaacagca gaggctaggg ttaatgtcga gacagggaac 2040 agaaggtaga cacaggaaca gacagagacg ggggagccag gtaacaaagg aatggtcctt 2100 ctcacctgtg gccagagcgt ccatctgtgt ccacatactc tagaatgttc atcagactgc 2160 agggctggct tgggaggcag ctggaaagag tatgtgagag ccaggggaga caagggggcc 2220 taggaaagga agaagagggc aaaccaggcc acacaagagg gcagagccca gaactgagtt 2280 aactccttcc ttgttgcatc ttccatagga ggcagtggga actctgtgac caccatcccc 2340 catgagcccc cactacccat accaagtttg gcctgagtgg cattctaggt tccctgagga 2400 cagagcctgg cctttgtctc ttggacctga cccaagctga cccaatgttc tcagtacctt 2460 atcatgccct caagagcttg agaaccaggc agtgacatat taggccatgg gctaaccctg 2520 gagcttgcac acaggagcct caagtgacct ccagggacac agctgcagac aggtggcctt 2580 tatccccaaa gagcaaccat ttggcatagg tggctgcaaa tgggaatgca aggttgaatc 2640 aggtcccttc aagaatactg catgcaagac ctaagacccc tggagagagg ggtatgctcc 2700 tgcccccacc caccataagg ggagtgaact atcctagggg gctggcgacc ttggggagac 2760 accacattac tgagagtgct gagcccagaa aaactgaccg ccctgtgtcc tgcccacctc 2820 cacactctag agctatattg agaggtgaca gtagataggg tgggagctgg tagcagggag 2880 agtgttcctg ggtgtgaggg tgtaggggaa agccagagca ggggagtctg gctttgtctc 2940 ctgaacacaa tgtctactta gttataacag gcatgacctg ctaaagaccc aacatctacg 3000 acctctgaaa agacagcagc cctggaggac aggggttgtc tctgagcctt gggtgcttga 3060 tggtgccaca aaggagggca tgagtgtgag tataaggccc caggagcgtt agagaagggc 3120 acttgggaag gggtcagtct gcagagcccc tatccatgga atctggagcc tggggccaac 3180 tggtgtaaat ctctgggcct gccaggcatt caaagcagca cctgcatcct ctggcagcct 3240 ggggaggcgg aagggagcaa ccccccactt ataccctttc tccctcagcc ccaggattaa 3300 cacctctggc cttccccctt cccacctccc atcaggagtg gagggttgca gagggagggt 3360 aaaaacctac atgtccaaac atcatggtgc acgatatatg gatcagtatg tgtagaggca 3420 agaaaggaaa tctgcaggct taactgggtt aatgtgtaaa gtctgtgtgc atgtgtgtgt 3480 gtctgactga aaacgggcat ggctgtgcag ctgttcagtt ctgtgcgtga ggttaccaga 3540 ctgcaggttt gtgtgtaaat tgcccaaggc aaagtgggtg aatcccttcc atggtttaaa 3600 gagattggat gatggcctgc atctcaagga ccatggaaaa tagaatggac actctatatg 3660 tgtctctaag ctaaggtagc aaggtctttg gaggacacct gtctagagat gtgggcaaca 3720 gagactacag acagtatctg tacagagtaa ggagagagag gagggggtgt agaattctct 3780 tactatcaaa gggaaactga gtcgtgcacc tgcaaagtgg atgctctccc tagacatcat 3840 gactttgtct ctggggagcc agcactgtgg aacttcaggt ctgagagagt aggaggctcc 3900 cctcagcctg aagctatgca gatagccagg gttgaaaggg ggaagggaga gcctgggatg 3960 ggagcttgtg tgttggaggc aggggacaga tattaagcct ggaagagaag gtgaccctta 4020 cccagttgtt caactcaccc ttcagattaa aaataactga ggtaagggcc tgggtagggg 4080 aggtggtgtg agacgctcct gtctctcctc tatctgccca tcggcccttt ggggaggagg 4140 aatgtgccca aggactaaaa aaaggccatg gagccagagg ggcgagggca acagaccttt 4200 catgggcaaa ccttggggcc ctgctgtcct cctgtcacct ccagagccaa gggatcaaag 4260 gaggaggagc caggacagga gggaagtggg agggagggtc ccagcagagg actccaaatt 4320 taggcagcag gcatatggga tgggatataa aggggctgga gcactgagag ctgtcagaga 4380 tttctccaac ccaggtaaga gggagtttcg ggtgggggct cttcacccac accagacctc 4440 tccccaccta gaaggaaact gcctttcctg gaagtggggt tcaggccggt cagagatctg 4500 acagggtggc cttccaccag cctgggaagt tctcagtggc aggaggtttc cacaagaaac 4560 actggatgcc ccttccctta cgctgtcttc tccatcttcc tcctggggat gctcctcccc 4620 gtcttggttt atcttggctc ttcgtcttca gcaagatttg ccctgtgctg tccactccat 4680 ctttctctac tgtctccgtg ccttgccttg ccttcttgcg tgtccttcct ttccacccat 4740 ttctcacttc accttttctc cccttctcat ttgtattcat ccttccttcc ttccttcctt 4800 ccttccttcc ttccttcctt ccttcctttc tcccttcctt ccttccttcc ttccttcctt 4860 ccttccttcc ttcctgtgtc agagtgctga gaatcacacc tggggttccc acccttatgt 4920 aaacaatctt ccagtgagcc acagcttcag tgctgctggg tgctctctta ccttcctcac 4980 cccctggctt gtcctgttcc atcctggtca ggatctctag attggtctcc cagcctctgc 5040 tactcctctt cctgcctgtt cctctctctg tccagctgcg ccactgtggt gcctcgttcc 5100 agctgtggtc cacattcttc aggattctct gaaaagttaa ccaggtgaga atgtttcccc 5160 tgtagacagc agatcacgat tctcccggaa gtcaggcttc cagccctctc tttctctgcc 5220 cagctgcccg gcactcttag caaacctcag gcacccttac cccacataga cctctgacag 5280 agaagcaggc actttacatg gagtcctggt gggagagcca taggctacgg tgtaaaagag 5340 gcagggaagt ggtggtgtag gaaagtcagg acttcacata gaagcctagc ccacaccaga 5400 aatgacagac agatccctcc tatctccccc ataagagttt gagtcgaccc gcggccccga 5460 attg 5464 <210> SEQ ID NO 35 <211> LENGTH: 413 <212> TYPE: DNA <213> ORGANISM: Gallus gallus <400> SEQUENCE: 35 gggataaaag cagtctgggc tttcacatga cagcatctgg ggctgcggca gagggtcggg 60 tccgaagcgc tgccttatca gcgtccccag ccctgggagg tgacagctgg ctggcttgtg 120 tcagcccctc gggcactcac gtatctccgt ccgacgggtt taaaatagca aaactctgag 180 gccacacaat agcttgggct tatatgggct cctgtggggg aagggggagc acggaggggg 240 ccggggccgc tgctgccaaa atagcagctc acaagtgttg cattcctctc tgggcgccgg 300 gcacattcct gctggctctg cccgccccgg ggtgggcgcc ggggggacct taaagcctct 360 gccccccaag gagcccttcc cagacagccg ccggcaccca ccgctccgtg gga 413 <210> SEQ ID NO 36 <211> LENGTH: 1090 <212> TYPE: DNA <213> ORGANISM: Homo sapiens <400> SEQUENCE: 36 ctctcagccc tggaagtcct tgctcacagc cgaggcgccg agagcgcttg ctctgcccag 60 atctgcgcga gtctggcgcc cgcgctctga acggcgtcgc tgcccagccc ccttccccgg 120 gaggtgggag cggccaccca gggccccgtg gctgcccttg taaggaggcg aggcccgagg 180 acacccgaga cgcccggtta taattaacca ggacacgtgg cgaacccccc tccaacacct 240 gcccccgaac ccccccatac ccagcgcctc gggtctcggc ctttgcggca gaggagacag 300 caaagcgccc tctaaaaata actcctttcc cggcgaccga gaccctccct gtcccccgca 360 cagcggaaat ctcccagtgg caccgagggg gcgagggtta agtggggggg agggtgacca 420 ccgcctccca cccttgccct gagtttgaat ctctccaact cagccagcct cagtttcccc 480 tccactcagt ccctaggagg aaggggcgcc caagcgcggg tttctggggt tagactgccc 540 tccattgcaa ttggtccttc tcccggcctc tgcttcctcc agctcacagg gtatctgctc 600 ctcctggagc cacaccttgg ttccccgagg tgccgctggg actcgggtag gggtgagggc 660 ccagggggca cagggggagc cgagggccac aggaagggct ggtggctgaa ggagactcag 720 gggccagggg acggtggctt ctacgtgctt gggacgttcc cagccaccgt cccatgttcc 780 cggcgggggg ccagctgtcc ccaccgccag cccaactcag cacttggtca gggtatcagc 840 ttggtggggg ggcgtgagcc cagcccctgg ggcggctcag cccatacaag gccatggggc 900 tgggcgcaaa gcatgcctgg gttcagggtg ggtatggtgc gggagcaggg aggtgagagg 960 ctcagctgcc ctccagaact cctccctggg gacaacccct cccagccaat agcacagcct 1020 aggtccccct atataaggcc acggctgctg gcccttcctt tgggtcagtg tcacctccag 1080 gatacagaca 1090 <210> SEQ ID NO 37 <211> LENGTH: 253 <212> TYPE: DNA <213> ORGANISM: Homo sapiens <400> SEQUENCE: 37 gcccagcacc ccaaggcggc caacgccaaa actctccctc ctcctcttcc tcaatctcgc 60 tctcgctctt tttttttttc gcaaaaggag gggagagggg gtaaaaaaat gctgcactgt 120 gcggcgaagc cggtgagtga gcggcgcggg gccaatcagc gtgcgccgtt ccgaaagttg 180 ccttttatgg ctcgagcggc cgcggcggcg ccctataaaa cccagcggcg cgacgcgcca 240 ccaccgccga gtc 253 <210> SEQ ID NO 38 <211> LENGTH: 281 <212> TYPE: DNA <213> ORGANISM: Gallus gallus <400> SEQUENCE: 38 ggtcgaggtg agccccacgt tctgcttcac tctccccatc tcccccccct ccccaccccc 60 aattttgtat ttatttattt tttaattatt ttgtgcagcg atgggggcgg gggggggggg 120 ggcgcgcgcc aggcggggcg gggcggggcg aggggcgggg cggggcgagg cggagaggtg 180 cggcggcagc caatcagagc ggcgcgctcc gaaagtttcc ttttatggcg aggcggcggc 240 ggcggcggcc ctataaaaag cgaagcgcgc ggcgggcggg a 281 <210> SEQ ID NO 39 <211> LENGTH: 220 <212> TYPE: DNA <213> ORGANISM: Human betaherpesvirus 5 <400> SEQUENCE: 39 tggtgatgcg gttttggcag tacaccaatg ggcgtggata gcggtttgac tcacggggat 60 ttccaagtct ccaccccatt gacgtcaatg ggagtttgtt ttggcaccaa aatcaacggg 120 actttccaaa atgtcgtaat aaccccgccc cgttgacgca aatgggcggt aggcgtgtac 180 ggtgggaggt ctatataagc agagctcgtt tagtgaaccg 220 <210> SEQ ID NO 40 <211> LENGTH: 583 <212> TYPE: DNA <213> ORGANISM: Human betaherpesvirus 5 <400> SEQUENCE: 40 tagttattaa tagtaatcaa ttacggggtc attagttcat agcccatata tggagttccg 60 cgttacataa cttacggtaa atggcccgcc tggctgaccg cccaacgacc cccgcccatt 120 gacgtcaata atgacgtatg ttcccatagt aacgccaata gggactttcc attgacgtca 180 atgggtggag tatttacggt aaactgccca cttggcagta catcaagtgt atcatatgcc 240 aagtacgccc cctattgacg tcaatgacgg taaatggccc gcctggcatt atgcccagta 300 catgacctta tgggactttc ctacttggca gtacatctac gtattagtca tcgctattac 360 catggtgatg cggttttggc agtacatcaa tgggcgtgga tagcggtttg actcacgggg 420 atttccaagt ctccacccca ttgacgtcaa tgggagtttg ttttggcacc aaaatcaacg 480 ggactttcca aaatgtcgta acaactccgc cccattgacg caaatgggcg gtaggcgtgt 540 acggtgggag gtctatataa gcagagctgg tttagtgaac cgt 583 <210> SEQ ID NO 41 <211> LENGTH: 508 <212> TYPE: DNA <213> ORGANISM: Human betaherpesvirus 5 <400> SEQUENCE: 41 cgttacataa cttacggtaa atggcccgcc tggctgaccg cccaacgacc cccgcccatt 60 gacgtcaata atgacgtatg ttcccatagt aacgccaata gggactttcc attgacgtca 120 atgggtggag tatttacggt aaactgccca cttggcagta catcaagtgt atcatatgcc 180 aagtacgccc cctattgacg tcaatgacgg taaatggccc gcctggcatt atgcccagta 240 catgacctta tgggactttc ctacttggca gtacatctac gtattagtca tcgctattac 300 catggtgatg cggttttggc agtacatcaa tgggcgtgga tagcggtttg actcacgggg 360 atttccaagt ctccacccca ttgacgtcaa tgggagtttg ttttggcacc aaaatcaacg 420 ggactttcca aaatgtcgta acaactccgc cccattgacg caaatgggcg gtaggcgtgt 480 acggtgggag gtctatataa gcagagct 508 <210> SEQ ID NO 42 <211> LENGTH: 573 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Made in lab - CAG promoter in part Human betaherpesvirus 5 <400> SEQUENCE: 42 acttacggta aatggcccgc ctggctgacc gcccaacgac ccccgcccat tgacgtcaat 60 aatgacgtat gttcccatag taacgccaat agggactttc cattgacgtc aatgggtgga 120 gtatttacgg taaactgccc acttggcagt acatcaagtg tatcatatgc caagtacgcc 180 ccctattgac gtcaatgacg gtaaatggcc cgcctggcat tatgcccagt acatgacctt 240 atgggacttt cctacttggc agtacatcta cgtattagtc atcgctatta ccatggtcga 300 ggtgagcccc acgttctgct tcactctccc catctccccc ccctccccac ccccaatttt 360 gtatttattt attttttaat tattttgtgc agcgatgggg gcgggggggg ggggggcgcg 420 cgccaggcgg ggcggggcgg ggcgaggggc ggggcggggc gaggcggaga ggtgcggcgg 480 cagccaatca gagcggcgcg ctccgaaagt ttccttttat ggcgaggcgg cggcggcggc 540 ggccctataa aaagcgaagc gcgcggcggg cgg 573 <210> SEQ ID NO 43 <211> LENGTH: 580 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Made in lab - CAG promoter in part Human betaherpesvirus 5 <400> SEQUENCE: 43 cgttacataa cttacggtaa atggcccgcc tggctgaccg cccaacgacc cccgcccatt 60 gacgtcaata atgacgtatg ttcccatagt aacgccaata gggactttcc attgacgtca 120 atgggtggag tatttacggt aaactgccca cttggcagta catcaagtgt atcatatgcc 180 aagtacgccc cctattgacg tcaatgacgg taaatggccc gcctggcatt atgcccagta 240 catgacctta tgggactttc ctacttggca gtacatctac gtattagtca tcgctattac 300 catgtcgagg tgagccccac gttctgcttc actctcccca tctccccccc ctccccaccc 360 ccaattttgt atttatttat tttttaatta ttttgtgcag cgatgggggc gggggggggg 420 ggggcgcgcg ccaggcgggg cggggcgggg cgaggggcgg ggcggggcga ggcggagagg 480 tgcggcggca gccaatcaga gcggcgcgct ccgaaagttt ccttttatgg cgaggcggcg 540 gcggcggcgg ccctataaaa agcgaagcgc gcggcgggcg 580 <210> SEQ ID NO 44 <211> LENGTH: 455 <212> TYPE: DNA <213> ORGANISM: Homo sapiens <400> SEQUENCE: 44 caacctttgg agctaagcca gcaatggtag agggaagatt ctgcacgtcc cttccaggcg 60 gcctccccgt caccaccccc cccaacccgc cccgaccgga gctgagagta attcatacaa 120 aaggactcgc ccctgccttg gggaatccca gggaccgtcg ttaaactccc actaacgtag 180 aacccagaga tcgctgcgtt cccgccccct cacccgcccg ctctcgtcat cactgaggtg 240 gagaatagca tgcgtgaggc tccggtgccc gtcagtgggc agagcgcaca tcgcccacag 300 tccccgagaa gttgggggga ggggtcggca attgaacggg tgcctagaga aggtggcgcg 360 gggtaaactg ggaaagtgat gtcgtgtact ggctccgcct ttttcccgag ggtgggggag 420 aaccgtatat aagtgcagta gtcgccgtga acgtt 455 <210> SEQ ID NO 45 <400> SEQUENCE: 45 000 <210> SEQ ID NO 46 <400> SEQUENCE: 46 000 <210> SEQ ID NO 47 <400> SEQUENCE: 47 000 <210> SEQ ID NO 48 <211> LENGTH: 281 <212> TYPE: DNA <213> ORGANISM: Homo sapiens <400> SEQUENCE: 48 acttgtggac aaagtttgct ctattccacc tcctccaggc cctccttggg tccatcaccc 60 caggggtgct gggtccatcc cacccccagg cccacacagg cttgcagtat tgtgtgcggt 120 atggtcaggg cgtccgagag caggtttcgc agtggaaggc aggcaggtgt tggggaggca 180 gttaccgggg caacgggaac agggcgtttt ggaggtggtt gccatgggga cctggatgct 240 gacgaaggct cgcgaggctg tgagcagcca cagtgccctg c 281 <210> SEQ ID NO 49 <400> SEQUENCE: 49 000 <210> SEQ ID NO 50 <211> LENGTH: 293 <212> TYPE: DNA <213> ORGANISM: Human betaherpesvirus 5 <400> SEQUENCE: 50 acttacggta aatggcccgc ctggctgacc gcccaacgac ccccgcccat tgacgtcaat 60 aatgacgtat gttcccatag taacgccaat agggactttc cattgacgtc aatgggtgga 120 gtatttacgg taaactgccc acttggcagt acatcaagtg tatcatatgc caagtacgcc 180 ccctattgac gtcaatgacg gtaaatggcc cgcctggcat tatgcccagt acatgacctt 240 atgggacttt cctacttggc agtacatcta cgtattagtc atcgctatta cca 293 <210> SEQ ID NO 51 <211> LENGTH: 953 <212> TYPE: DNA <213> ORGANISM: Homo sapiens <400> SEQUENCE: 51 cgcgtccgcc cgcgagcaca gagcctcgcc tttgccgatc cgccgcccgt ccacacccgc 60 cgccaggtaa gcccggccag ccgaccgggg catgcggccg cggcccttcg cccgtgcaga 120 gccgccgtct gggccgcagc ggggggcgca tggggcggaa ccggaccgcc gtggggggcg 180 cgggagaagc ccctgggcct ccggagatgg gggacacccc acgccagttc gcaggcgcga 240 ggccgcgctc gggcgggcgc gctccggggg tgccgctctc ggggcggggg caaccggcgg 300 ggtctttgtc tgagccgggc tcttgccaat ggggatcgca cggtgggcgc ggcgtagccc 360 ccgtcaggcc cggtgggggc tggggcgcca tgcgcgtgcg cgctggtcct ttgggcgcta 420 actgcgtgcg cgctgggaat tggcgctaat tgcgcgtgcg cgctgggact caatggcgct 480 aatcgcgcgt gcgttctggg gcccgggcgc ttgcgccact tcctgcccga gccgctggcg 540 cccgagggtg tggccgctgc gtgcgcgcgc gcgacccggt cgctgtttga accgggcgga 600 ggcggggctg gcgcccggtt gggagggggt tggggcctgg cttcctgccg cgcgccgcgg 660 ggacgcctcc gaccagtgtt tgccttttat ggtaataacg cggccggccc ggcttccttt 720 gtccccaatc tgggcgcgcg ccggcgcccc ctggcggcct aaggactcgg cgcgccggaa 780 gtggccaggg cggcagcggc tgctcttggc ggccccgagg tgactatagc cttcttttgt 840 gtcttgatag ttcgccagcc tctgctaacc atgttcatgc cttcttcttt ttcctacagc 900 tcctgggcaa cgtgctggtt attgtgctgt ctcatcattt tggcaaagaa ttc 953 <210> SEQ ID NO 52 <211> LENGTH: 1068 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Made in Lab - Chicken beta-actin exon/intron plus rabbit globin intron <400> SEQUENCE: 52 gtcgctgcgc gctgccttcg ccccgtgccc cgctccgccg ccgcctcgcg ccgcccgccc 60 cggctctgac tgaccgcgtt actcccacag gtgagcgggc gggacggccc ttctcctccg 120 ggctgtaatt agcgcttggt ttaatgacgg cttgtttctt ttctgtggct gcgtgaaagc 180 cttgaggggc tccgggaggg ccctttgtgc ggggggagcg gctcgggggg tgcgtgcgtg 240 tgtgtgtgcg tggggagcgc cgcgtgcggc tccgcgctgc ccggcggctg tgagcgctgc 300 gggcgcggcg cggggctttg tgcgctccgc agtgtgcgcg aggggagcgc ggccgggggc 360 ggtgccccgc ggtgcggggg gggctgcgag gggaacaaag gctgcgtgcg gggtgtgtgc 420 gtgggggggt gagcaggggg tgtgggcgcg tcggtcgggc tgcaaccccc cctgcacccc 480 cctccccgag ttgctgagca cggcccggct tcgggtgcgg ggctccgtac ggggcgtggc 540 gcggggctcg ccgtgccggg cggggggtgg cggcaggtgg gggtgccggg cggggcgggg 600 ccgcctcggg ccggggaggg ctcgggggag gggcgcggcg gcccccggag cgccggcggc 660 tgtcgaggcg cggcgagccg cagccattgc cttttatggt aatcgtgcga gagggcgcag 720 ggacttcctt tgtcccaaat ctgtgcggag ccgaaatctg ggaggcgccg ccgcaccccc 780 tctagcgggc gcggggcgaa gcggtgcggc gccggcagga aggaaatggg cggggagggc 840 cttcgtgcgt cgccgcgccg ccgtcccctt ctccctctcc agcctcgggg ctgtccgcgg 900 ggggacggct gccttcgggg gggacggggc agggcggggt tcggcttctg gcgtgtgacc 960 ggcggctcta gagcctctgc taaccatgtt catgccttct tctttttcct acagctcctg 1020 ggcaacgtgc tggttattgt gctgtctcat cattttggca aagaattc 1068 <210> SEQ ID NO 53 <211> LENGTH: 149 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Made in Lab - chimeric intron sequence <400> SEQUENCE: 53 ggtaagttta gtctttttgt cttttatttc aggtcccgga tccggtggtg gtgcaaatca 60 aagaactgct cctcagtgga tgttgccttt acttctaggc ctgtacggaa gtgttacttc 120 tgctctaaaa gctgcggaat tgtacccgc 149 <210> SEQ ID NO 54 <211> LENGTH: 126 <212> TYPE: DNA <213> ORGANISM: Homo sapiens <400> SEQUENCE: 54 agtctgcggt gggcagcgga ggagtcgtgt cgtgcctgag agcgcagctg tgctcctggg 60 caccgcgcag tccgcccccg cggctcctgg ccagaccacc cctaggaccc cctgccccaa 120 gtcgca 126 <210> SEQ ID NO 55 <211> LENGTH: 121 <212> TYPE: DNA <213> ORGANISM: Human betaherpesvirus 5 <400> SEQUENCE: 55 tcagatcgcc tggagaggcc atccacgctg ttttgacctc catagtggac accgggaccg 60 atccagcctc cgcggccggg aacggtgcat tggaacgcgg attccccgtg ccaagagtga 120 c 121 <210> SEQ ID NO 56 <211> LENGTH: 512 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Made in Lab - adenovirus derived enhancer element <400> SEQUENCE: 56 ctcactctct tccgcatcgc tgtctgcgag ggccagctgt tgggctcgcg gttgaggaca 60 aactcttcgc ggtctttcca gtactcttgg atcggaaacc cgtcggcctc cgaacggtac 120 tccgccaccg agggacctga gcgagtccgc atcgaccgga tcggaaaacc tctcgagaaa 180 ggcgtctaac cagtcacagt cgcaaggtag gctgagcacc gtggcgggcg gcagcgggtg 240 gcggtcgggg ttgtttctgg cggaggtgct gctgatgatg taattaaagt aggcggtctt 300 gagacggcgg atggtcgagg tgaggtgtgg caggcttgag atccagctgt tggggtgagt 360 actccctctc aaaagcgggc attacttctg cgctaagatt gtcagtttcc aaaaacgagg 420 aggatttgat attcacctgg cccgatctgg ccatacactt gagtgacaat gacatccact 480 ttgcctttct ctccacaggt gtccactccc ag 512 <210> SEQ ID NO 57 <211> LENGTH: 956 <212> TYPE: DNA <213> ORGANISM: Homo sapiens <400> SEQUENCE: 57 ctttttcgca acgggtttgc cgccagaaca caggtaagtg ccgtgtgtgg ttcccgcggg 60 cctggcctct ttacgggtta tggcccttgc gtgccttgaa ttacttccac ctggctccag 120 tacgtgattc ttgatcccga gctggagcca ggggcgggcc ttgcgcttta ggagcccctt 180 cgcctcgtgc ttgagttgag gcctggcctg ggcgctgggg ccgccgcgtg cgaatctggt 240 ggcaccttcg cgcctgtctc gctgctttcg ataagtctct agccatttaa aatttttgat 300 gacgtgctgc gacgcttttt ttctggcaag atagtcttgt aaatgcgggc caggatctgc 360 acactggtat ttcggttttt gggcccgcgg ccggcgacgg ggcccgtgcg tcccagcgca 420 catgttcggc gaggcggggc ctgcgagcgc ggccaccgag aatcggacgg gggtagtctc 480 aagctggccg gcctgctctg gtgcctggcc tcgcgccgcc gtgtatcgcc ccgccctggg 540 cggcaaggct ggcccggtcg gcaccagttg cgtgagcgga aagatggccg cttcccggcc 600 ctgctccagg gggctcaaaa tggaggacgc ggcgctcggg agagcgggcg ggtgagtcac 660 ccacacaaag gaaaagggcc tttccgtcct cagccgtcgc ttcatgtgac tccacggagt 720 accgggcgcc gtccaggcac ctcgattagt tctggagctt ttggagtacg tcgtctttag 780 gttgggggga ggggttttat gcgatggagt ttccccacac tgagtgggtg gagactgaag 840 ttaggccagc ttggcacttg atgtaattct ccttggaatt tggccttttt gagtttggat 900 cttggttcat tctcaagcct cagacagtgg ttcaaagttt ttttcttcca tttcag 956 <210> SEQ ID NO 58 <211> LENGTH: 939 <212> TYPE: DNA <213> ORGANISM: Homo sapiens <400> SEQUENCE: 58 gtaagtgccg tgtgtggttc ccgcgggcct ggcctcttta cgggttatgg cccttgcgtg 60 ccttgaatta cttccacctg gctgcagtac gtgattcttg atcccgagct tcgggttgga 120 agtgggtggg agagttcgag gccttgcgct taaggagccc cttcgcctcg tgcttgagtt 180 gaggcctggc ctgggcgctg gggccgccgc gtgcgaatct ggtggcacct tcgcgcctgt 240 ctcgctgctt tcgataagtc tctagccatt taaaattttt gatgacctgc tgcgacgctt 300 tttttctggc aagatagtct tgtaaatgcg ggccaagatc tgcacactgg tatttcggtt 360 tttggggccg cgggcggcga cggggcccgt gcgtcccagc gcacatgttc ggcgaggcgg 420 ggcctgcgag cgcggccacc gagaatcgga cgggggtagt ctcaagctgg ccggcctgct 480 ctggtgcctg gcctcgcgcc gccgtgtatc gccccgccct gggcggcaag gctggcccgg 540 tcggcaccag ttgcgtgagc ggaaagatgg ccgcttcccg gccctgctgc agggagctca 600 aaatggagga cgcggcgctc gggagagcgg gcgggtgagt cacccacaca aaggaaaagg 660 gcctttccgt cctcagccgt cgcttcatgt gactccacgg agtaccgggc gccgtccagg 720 cacctcgatt agttctcgag cttttggagt acgtcgtctt taggttgggg ggaggggttt 780 tatgcgatgg agtttcccca cactgagtgg gtggagactg aagttaggcc agcttggcac 840 ttgatgtaat tctccttgga atttgccctt tttgagtttg gatcttggtt cattctcaag 900 cctcagacag tggttcaaag tttttttctt ccatttcag 939 <210> SEQ ID NO 59 <211> LENGTH: 83 <212> TYPE: DNA <213> ORGANISM: Homo sapiens <400> SEQUENCE: 59 tcagaagccc cgggctcgtc agtcaaaccg gttctctgtt tgcactcggc agcacgggca 60 ggcaagtggt ccctaggttc ggg 83 <210> SEQ ID NO 60 <211> LENGTH: 476 <212> TYPE: DNA <213> ORGANISM: Homo sapiens <400> SEQUENCE: 60 gtgagtctat gggacccttg atgttttctt tccccttctt ttctatggtt aagttcatgt 60 cataggaagg ggagaagtaa cagggtacac atattgacca aatcagggta attttgcatt 120 tgtaatttta aaaaatgctt tcttctttta atatactttt ttgtttatct tatttctaat 180 actttcccta atctctttct ttcagggcaa taatgataca atgtatcatg cctctttgca 240 ccattctaaa gaataacagt gataatttct gggttaaggc aatagcaata tttctgcata 300 taaatatttc tgcatataaa ttgtaactga tgtaagaggt ttcatattgc taatagcagc 360 tacaatccag ctaccattct gcttttattt tatggttggg ataaggctgg attattctga 420 gtccaagcta ggcccttttg ctaatcatgt tcatacctct tatcttcctc ccacag 476 <210> SEQ ID NO 61 <211> LENGTH: 196 <212> TYPE: DNA <213> ORGANISM: simian virus 40 <400> SEQUENCE: 61 tctagaggat ccggtactcg aggaactgaa aaaccagaaa gttaactggt aagtttagtc 60 tttttgtctt ttatttcagg tcccggatcc ggtggtggtg caaatcaaag aactgctcct 120 cagtggatgt tgcctttact tctaggcctg tacggaagtg ttacttctgc tctaaaagct 180 gcggaattgt acccgc 196 <210> SEQ ID NO 62 <211> LENGTH: 589 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Made in Lab - mutated woodchuck hepatitis regulatory element <400> SEQUENCE: 62 aatcaacctc tggattacaa aatttgtgaa agattgactg gtattcttaa ctatgttgct 60 ccttttacgc tatgtggata cgctgcttta atgcctttgt atcatgctat tgcttcccgt 120 atggctttca ttttctcctc cttgtataaa tcctggttgc tgtctcttta tgaggagttg 180 tggcccgttg tcaggcaacg tggcgtggtg tgcactgtgt ttgctgacgc aacccccact 240 ggttggggca ttgccaccac ctgtcagctc ctttccggga ctttcgcttt ccccctccct 300 attgccacgg cggaactcat cgccgcctgc cttgcccgct gctggacagg ggctcggctg 360 ttgggcactg acaattccgt ggtgttgtcg gggaaatcat cgtcctttcc ttggctgctc 420 gcctgtgttg ccacctggat tctgcgcggg acgtccttct gctacgtccc ttcggccctc 480 aatccagcgg accttccttc ccgcggcctg ctgccggctc tgcggcctct tccgcgtctt 540 cgccttcgcc ctcagacgag tcggatctcc ctttgggccg cctccccgc 589 <210> SEQ ID NO 63 <211> LENGTH: 588 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Made in Lab - mutated woodchuck hepatitis regulatory element <400> SEQUENCE: 63 tcaacctctg gattacaaaa tttgtgaaag attgactggt attcttaact atgttgctcc 60 ttttacgcta tgtggatacg ctgctttaat gcctttgtat catgctattg cttcccgtat 120 ggctttcatt ttctcctcct tgtataaatc ctggttgctg tctctttatg aggagttgtg 180 gcccgttgtc aggcaacgtg gcgtggtgtg cactgtgttt gctgacgcaa cccccactgg 240 ttggggcatt gccaccacct gtcagctcct ttccgggact ttcgctttcc ccctccctat 300 tgccacggcg gaactcatcg ccgcctgcct tgcccgctgc tggacagggg ctcggctgtt 360 gggcactgac aattccgtgg tgttgtcggg gaaatcatcg tcctttcctt ggctgctcgc 420 ctgtgttgcc acctggattc tgcgcgggac gtccttctgc tacgtccctt cggccctcaa 480 tccagcggac cttccttccc gcggcctgct gccggctctg cggcctcttc cgcgtcttcg 540 ccttcgccct cagacgagtc ggatctccct ttgggccgcc tccccgca 588 <210> SEQ ID NO 64 <211> LENGTH: 755 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Made in Lab - mutated woodchuck hepatitis regulatory element <400> SEQUENCE: 64 ttcctgttaa tcaacctctg gattacaaaa tttgtgaaag attgactggt attcttaact 60 atgttgctcc ttttacgcta tgtggatacg ctgctttaat gcctttgtat catgctattg 120 cttcccgtat ggctttcatt ttctcctcct tgtataaatc ctggttgctg tctctttatg 180 aggagttgtg gcccgttgtc aggcaacgtg gcgtggtgtg cactgtgttt gctgacgcaa 240 cccccactgg ttggggcatt gccaccacct gtcagctcct ttccgggact ttcgctttcc 300 ccctccctat tgccacggcg gaactcatcg ccgcctgcct tgcccgctgc tggacagggg 360 ctcggctgtt gggcactgac aattccgtgg tgttgtcggg gaagctgacg tcctttccgc 420 ggctgctcgc ctgtgttgcc acctggattc tgcgcgggac gtccttctgc tacgtccctt 480 cggccctcaa tccagcggac cttccttccc gcggcctgct gccggctctg cggcctcttc 540 cgcctcttcg ccttcgccct cagacgagtc ggatctccct ttgggccgcc tccccgccca 600 tgtatctttt tcacctgtgc cttgtttttg cctgtgttcc gcgtcctact tttcaagcct 660 ccaagctgtg ccttgggcgg ctttggggca tggacataga tccctataaa gaatttggtt 720 catcttatca gttgttgaat tttcttcctt tggac 755 <210> SEQ ID NO 65 <211> LENGTH: 12 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: CAAX motif <400> SEQUENCE: 65 tgtgtgataa tg 12 <210> SEQ ID NO 66 <211> LENGTH: 810 <212> TYPE: DNA <213> ORGANISM: Homo sapiens <400> SEQUENCE: 66 ctgttctcat cacatcatat caaggttata taccatcaat attgccacag atgttactta 60 gccttttaat atttctctaa tttagtgtat atgcaatgat agttctctga tttctgagat 120 tgagtttctc atgtgtaatg attatttaga gtttctcttt catctgttca aatttttgtc 180 tagttttatt ttttactgat ttgtaagact tctttttata atctgcatat tacaattctc 240 tttactgggg tgttgcaaat attttctgtc attctatggc ctgacttttc ttaatggttt 300 tttaatttta aaaataagtc ttaatattca tgcaatctaa ttaacaatct tttctttgtg 360 gttaggactt tgagtcataa gaaatttttc tctacactga agtcatgatg gcatgcttct 420 atattatttt ctaaaagatt taaagttttg ccttctccat ttagacttat aattcactgg 480 aatttttttg tgtgtatggt atgacatatg ggttcccttt tattttttac atataaatat 540 atttccctgt ttttctaaaa aagaaaaaga tcatcatttt cccattgtaa aatgccatat 600 ttttttcata ggtcacttac atatatcaat gggtctgttt ctgagctcta ctctatttta 660 tcagcctcac tgtctatccc cacacatctc atgctttgct ctaaatcttg atatttagtg 720 gaacattctt tcccattttg ttctacaaga atatttttgt tattgtcttt gggctttcta 780 tatacatttt gaaatgaggt tgacaagtta 810 <210> SEQ ID NO 67 <211> LENGTH: 726 <212> TYPE: DNA <213> ORGANISM: Hepatitis B virus <400> SEQUENCE: 67 ataacaggcc tattgattgg aaagtttgtc aacgaattgt gggtcttttg gggtttgctg 60 ccccttttac gcaatgtgga tatcctgctt taatgccttt atatgcatgt atacaagcaa 120 aacaggcttt tactttctcg ccaacttaca aggcctttct cagtaaacag tatatgaccc 180 tttaccccgt tgctcggcaa cggcctggtc tgtgccaagt gtttgctgac gcaaccccca 240 ctggttgggg cttggccata ggccatcagc gcatgcgtgg aacctttgtg tctcctctgc 300 cgatccatac tgcggaactc ctagccgctt gttttgctcg cagcaggtct ggagcaaacc 360 tcatcgggac cgacaattct gtcgtactct cccgcaagta tacatcgttt ccatggctgc 420 taggctgtgc tgccaactgg atcctgcgcg ggacgtcctt tgtttacgtc ccgtcggcgc 480 tgaatcccgc ggacgacccc tcccggggcc gcttggggct ctaccgcccg cttctccgtc 540 tgccgtaccg tccgaccacg gggcgcacct ctctttacgc ggactccccg tctgtgcctt 600 ctcatctgcc ggaccgtgtg cacttcgctt cacctctgca cgtcgcatgg aggccaccgt 660 gaacgcccac cggaacctgc ccaaggtctt gcataagagg actcttggac tttcagcaat 720 gtcatc 726 <210> SEQ ID NO 68 <211> LENGTH: 755 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Made in Lab - HepB derived enhancer element <400> SEQUENCE: 68 ttcctgtaaa caggcctatt gattggaaag tttgtcaacg aattgtgggt cttttggggt 60 ttgctgcccc ttttacgcaa tgtggatatc ctgctttaat gcctttatat gcatgtatac 120 aagcaaaaca ggcttttact ttctcgccaa cttacaaggc ctttctcagt aaacagtata 180 tgacccttta ccccgttgct cggcaacggc ctggtctgtg ccaagtgttt gctgacgcaa 240 cccccactgg ttggggcttg gccataggcc atcagcgcat gcgtggaacc tttgtgtctc 300 ctctgccgat ccatactgcg gaactcctag ccgcttgttt tgctcgcagc tggactggag 360 caaacctcat cgggaccgac aattctgtcg tactctcccg caagcactca ccgtttccgc 420 ggctgctcgc ctgtgttgcc acctggattc tgcgcgggac gtccttctgc tacgtccctt 480 cggccctcaa tccagcggac cttccttccc gcggcctgct gccggctctg cggcctcttc 540 cgcctcttcg ccttcgccct cagacgagtc ggatctccct ttgggccgcc tccccgccca 600 tgtatctttt tcacctgtgc cttgtttttg cctgtgttcc gcgtcctact tttcaagcct 660 ccaagctgtg ccttgggcgg ctttggggca tggacataga tccctataaa gaatttggtt 720 catcttatca gttgttgaat tttcttcctt tggac 755 <210> SEQ ID NO 69 <211> LENGTH: 94 <212> TYPE: DNA <213> ORGANISM: Homo sapiens <400> SEQUENCE: 69 gctggagcct cggtagccgt tcctcctgcc cgctgggcct cccaacgggc cctcctcccc 60 tccttgcacc ggcccttcct ggtctttgaa taaa 94 <210> SEQ ID NO 70 <211> LENGTH: 596 <212> TYPE: DNA <213> ORGANISM: Woodchuck hepatitis virus <400> SEQUENCE: 70 attcgagcat cttaccgcca tttattccca tatttgttct gtttttcttg atttgggtat 60 acatttaaat gttaataaaa caaaatggtg gggcaatcat ttacattttt agggatatgt 120 aattactagt tcaggtgtat tgccacaaga caaacatgtt aagaaacttt cccgttattt 180 acgctctgtt cctgttaatc aacctctgga ttacaaaatt tgtgaaagat tgactgatat 240 tcttaactat gttgctcctt ttacgctgtg tggatatgct gctttaatgc ctctgtatca 300 tgctattgct tcccgtacgg ctttcgtttt ctcctccttg tataaatcct ggttgctgtc 360 tctttatgag gagttgtggc ccgttgtccg tcaacgtggc gtggtgtgct ctgtgtttgc 420 tgacgcaacc cccactggct ggggcattgc caccacctgt caactccttt ctgggacttt 480 cgctttcccc ctcccgatcg ccacggcaga actcatcgcc gcctgccttg cccgctgctg 540 gacaggggct aggttgctgg gcactgataa ttccgtggtg ttgtcgggga agggcc 596 <210> SEQ ID NO 71 <211> LENGTH: 387 <212> TYPE: DNA <213> ORGANISM: Oryctolagus cuniculus <400> SEQUENCE: 71 tggctaataa aggaaattta ttttcattgc aatagtgtgt tggaattttt tgtgtctctc 60 actcggaaga acatatggga gggcaaatca tttaaaacat cagaatgagt atttggttta 120 gagtttggca acatatgccc atatgctggc tgccatgaac aaaggttggc tataaagagg 180 tcatcagtat atgaaacagc cccctgctgt ccattcctta ttccatagaa aagccttgac 240 ttgaggttag atttttttta tattttgttt tgtgttattt ttttctttaa catccctaaa 300 attttcctta catgttttac tagccagatt tttcctcctc tcctgactac tcccagtcat 360 agctgtccct cttctcttat ggagatc 387 <210> SEQ ID NO 72 <211> LENGTH: 251 <212> TYPE: DNA <213> ORGANISM: Bos taurus <400> SEQUENCE: 72 ttgccagcca tctgttgttt gcccctcccc cgtgccttcc ttgaccctgg aaggtgccac 60 tcccactgtc ctttcctaat aaaatgagga aattgcatcg cattgtctga gtaggtgtca 120 ttctattctg gggggtgggg tggggcagga cagcaagggg gaggattggg aatacaatag 180 caggcatgct ggggatgcgg tgggctctat gggtacccag gtgctgaaga attgacccgg 240 ttcctcctgg g 251 <210> SEQ ID NO 73 <211> LENGTH: 251 <212> TYPE: DNA <213> ORGANISM: Bos taurus <400> SEQUENCE: 73 ttgccagcca tctgttgttt gcccctcccc cgtgccttcc ttgaccctgg aaggtgccac 60 tcccactgtc ctttcctaat aaaatgagga aattgcatcg cattgtctga gtaggtgtca 120 ttctattctg gggggtgggg tggggcagga cagcaagggg gaggattggg aagacaatag 180 caggcatgct ggggatgcgg tgggctctat gggtacccag gtgctgaaga attgacccgg 240 ttcctcctgg g 251 <210> SEQ ID NO 74 <211> LENGTH: 225 <212> TYPE: DNA <213> ORGANISM: Bos taurus <400> SEQUENCE: 74 ctgtgccttc tagttgccag ccatctgttg tttgcccctc ccccgtgcct tccttgaccc 60 tggaaggtgc cactcccact gtcctttcct aataaaatga ggaaattgca tcgcattgtc 120 tgagtaggtg tcattctatt ctggggggtg gggtggggca ggacagcaag ggggaggatt 180 gggaagacaa tagcaggcat gctggggatg cggtgggctc tatgg 225 <210> SEQ ID NO 75 <211> LENGTH: 202 <212> TYPE: DNA <213> ORGANISM: Homo sapiens <400> SEQUENCE: 75 ctgcccgggt ggcatccctg tgacccctcc ccagtgcctc tcctggccct ggaagttgcc 60 actccagtgc ccaccagcct tgtcctaata aaattaagtt gcatcatttt gtctgactag 120 gtgtccttct ataatattat ggggtggagg ggggtggtat ggagcaaggg gcccaagttg 180 ggaagaaacc tgtagggcct gc 202 <210> SEQ ID NO 76 <211> LENGTH: 735 <212> TYPE: PRT <213> ORGANISM: Adeno-associated virus 2 <400> SEQUENCE: 76 Met Ala Ala Asp Gly Tyr Leu Pro Asp Trp Leu Glu Asp Thr Leu Ser 1 5 10 15 Glu Gly Ile Arg Gln Trp Trp Lys Leu Lys Pro Gly Pro Pro Pro Pro 20 25 30 Lys Pro Ala Glu Arg His Lys Asp Asp Ser Arg Gly Leu Val Leu Pro 35 40 45 Gly Tyr Lys Tyr Leu Gly Pro Phe Asn Gly Leu Asp Lys Gly Glu Pro 50 55 60 Val Asn Glu Ala Asp Ala Ala Ala Leu Glu His Asp Lys Ala Tyr Asp 65 70 75 80 Arg Gln Leu Asp Ser Gly Asp Asn Pro Tyr Leu Lys Tyr Asn His Ala 85 90 95 Asp Ala Glu Phe Gln Glu Arg Leu Lys Glu Asp Thr Ser Phe Gly Gly 100 105 110 Asn Leu Gly Arg Ala Val Phe Gln Ala Lys Lys Arg Val Leu Glu Pro 115 120 125 Leu Gly Leu Val Glu Glu Pro Val Lys Thr Ala Pro Gly Lys Lys Arg 130 135 140 Pro Val Glu His Ser Pro Val Glu Pro Asp Ser Ser Ser Gly Thr Gly 145 150 155 160 Lys Ala Gly Gln Gln Pro Ala Arg Lys Arg Leu Asn Phe Gly Gln Thr 165 170 175 Gly Asp Ala Asp Ser Val Pro Asp Pro Gln Pro Leu Gly Gln Pro Pro 180 185 190 Ala Ala Pro Ser Gly Leu Gly Thr Asn Thr Met Ala Thr Gly Ser Gly 195 200 205 Ala Pro Met Ala Asp Asn Asn Glu Gly Ala Asp Gly Val Gly Asn Ser 210 215 220 Ser Gly Asn Trp His Cys Asp Ser Thr Trp Met Gly Asp Arg Val Ile 225 230 235 240 Thr Thr Ser Thr Arg Thr Trp Ala Leu Pro Thr Tyr Asn Asn His Leu 245 250 255 Tyr Lys Gln Ile Ser Ser Gln Ser Gly Ala Ser Asn Asp Asn His Tyr 260 265 270 Phe Gly Tyr Ser Thr Pro Trp Gly Tyr Phe Asp Phe Asn Arg Phe His 275 280 285 Cys His Phe Ser Pro Arg Asp Trp Gln Arg Leu Ile Asn Asn Asn Trp 290 295 300 Gly Phe Arg Pro Lys Arg Leu Asn Phe Lys Leu Phe Asn Ile Gln Val 305 310 315 320 Lys Glu Val Thr Gln Asn Asp Gly Thr Thr Thr Ile Ala Asn Asn Leu 325 330 335 Thr Ser Thr Val Gln Val Phe Thr Asp Ser Glu Tyr Gln Leu Pro Tyr 340 345 350 Val Leu Gly Ser Ala His Gln Gly Cys Leu Pro Pro Phe Pro Ala Asp 355 360 365 Val Phe Met Val Pro Gln Tyr Gly Tyr Leu Thr Leu Asn Asn Gly Ser 370 375 380 Gln Ala Val Gly Arg Ser Ser Phe Tyr Cys Leu Glu Tyr Phe Pro Ser 385 390 395 400 Gln Met Leu Arg Thr Gly Asn Asn Phe Thr Phe Ser Tyr Thr Phe Glu 405 410 415 Asp Val Pro Phe His Ser Ser Tyr Ala His Ser Gln Ser Leu Asp Arg 420 425 430 Leu Met Asn Pro Leu Ile Asp Gln Tyr Leu Tyr Tyr Leu Ser Arg Thr 435 440 445 Asn Thr Pro Ser Gly Thr Thr Thr Gln Ser Arg Leu Gln Phe Ser Gln 450 455 460 Ala Gly Ala Ser Asp Ile Arg Asp Gln Ser Arg Asn Trp Leu Pro Gly 465 470 475 480 Pro Cys Tyr Arg Gln Gln Arg Val Ser Lys Thr Ser Ala Asp Asn Asn 485 490 495 Asn Ser Glu Tyr Ser Trp Thr Gly Ala Thr Lys Tyr His Leu Asn Gly 500 505 510 Arg Asp Ser Leu Val Asn Pro Gly Pro Ala Met Ala Ser His Lys Asp 515 520 525 Asp Glu Glu Lys Phe Phe Pro Gln Ser Gly Val Leu Ile Phe Gly Lys 530 535 540 Gln Gly Ser Glu Lys Thr Asn Val Asp Ile Glu Lys Val Met Ile Thr 545 550 555 560 Asp Glu Glu Glu Ile Arg Thr Thr Asn Pro Val Ala Thr Glu Gln Tyr 565 570 575 Gly Ser Val Ser Thr Asn Leu Gln Arg Gly Asn Arg Gln Ala Ala Thr 580 585 590 Ala Asp Val Asn Thr Gln Gly Val Leu Pro Gly Met Val Trp Gln Asp 595 600 605 Arg Asp Val Tyr Leu Gln Gly Pro Ile Trp Ala Lys Ile Pro His Thr 610 615 620 Asp Gly His Phe His Pro Ser Pro Leu Met Gly Gly Phe Gly Leu Lys 625 630 635 640 His Pro Pro Pro Gln Ile Leu Ile Lys Asn Thr Pro Val Pro Ala Asn 645 650 655 Pro Ser Thr Thr Phe Ser Ala Ala Lys Phe Ala Ser Phe Ile Thr Gln 660 665 670 Tyr Ser Thr Gly Gln Val Ser Val Glu Ile Glu Trp Glu Leu Gln Lys 675 680 685 Glu Asn Ser Lys Arg Trp Asn Pro Glu Ile Gln Tyr Thr Ser Asn Tyr 690 695 700 Asn Lys Ser Val Asn Val Asp Phe Thr Val Asp Thr Asn Gly Val Tyr 705 710 715 720 Ser Glu Pro Arg Pro Ile Gly Thr Arg Tyr Leu Thr Arg Asn Leu 725 730 735 <210> SEQ ID NO 77 <211> LENGTH: 736 <212> TYPE: PRT <213> ORGANISM: Adeno-associated virus 9 <400> SEQUENCE: 77 Met Ala Ala Asp Gly Tyr Leu Pro Asp Trp Leu Glu Asp Asn Leu Ser 1 5 10 15 Glu Gly Ile Arg Glu Trp Trp Ala Leu Lys Pro Gly Ala Pro Gln Pro 20 25 30 Lys Ala Asn Gln Gln His Gln Asp Asn Ala Arg Gly Leu Val Leu Pro 35 40 45 Gly Tyr Lys Tyr Leu Gly Pro Gly Asn Gly Leu Asp Lys Gly Glu Pro 50 55 60 Val Asn Ala Ala Asp Ala Ala Ala Leu Glu His Asp Lys Ala Tyr Asp 65 70 75 80 Gln Gln Leu Lys Ala Gly Asp Asn Pro Tyr Leu Lys Tyr Asn His Ala 85 90 95 Asp Ala Glu Phe Gln Glu Arg Leu Lys Glu Asp Thr Ser Phe Gly Gly 100 105 110 Asn Leu Gly Arg Ala Val Phe Gln Ala Lys Lys Arg Leu Leu Glu Pro 115 120 125 Leu Gly Leu Val Glu Glu Ala Ala Lys Thr Ala Pro Gly Lys Lys Arg 130 135 140 Pro Val Glu Gln Ser Pro Gln Glu Pro Asp Ser Ser Ala Gly Ile Gly 145 150 155 160 Lys Ser Gly Ala Gln Pro Ala Lys Lys Arg Leu Asn Phe Gly Gln Thr 165 170 175 Gly Asp Thr Glu Ser Val Pro Asp Pro Gln Pro Ile Gly Glu Pro Pro 180 185 190 Ala Ala Pro Ser Gly Val Gly Ser Leu Thr Met Ala Ser Gly Gly Gly 195 200 205 Ala Pro Val Ala Asp Asn Asn Glu Gly Ala Asp Gly Val Gly Ser Ser 210 215 220 Ser Gly Asn Trp His Cys Asp Ser Gln Trp Leu Gly Asp Arg Val Ile 225 230 235 240 Thr Thr Ser Thr Arg Thr Trp Ala Leu Pro Thr Tyr Asn Asn His Leu 245 250 255 Tyr Lys Gln Ile Ser Asn Ser Thr Ser Gly Gly Ser Ser Asn Asp Asn 260 265 270 Ala Tyr Phe Gly Tyr Ser Thr Pro Trp Gly Tyr Phe Asp Phe Asn Arg 275 280 285 Phe His Cys His Phe Ser Pro Arg Asp Trp Gln Arg Leu Ile Asn Asn 290 295 300 Asn Trp Gly Phe Arg Pro Lys Arg Leu Asn Phe Lys Leu Phe Asn Ile 305 310 315 320 Gln Val Lys Glu Val Thr Asp Asn Asn Gly Val Lys Thr Ile Ala Asn 325 330 335 Asn Leu Thr Ser Thr Val Gln Val Phe Thr Asp Ser Asp Tyr Gln Leu 340 345 350 Pro Tyr Val Leu Gly Ser Ala His Glu Gly Cys Leu Pro Pro Phe Pro 355 360 365 Ala Asp Val Phe Met Ile Pro Gln Tyr Gly Tyr Leu Thr Leu Asn Asp 370 375 380 Gly Ser Gln Ala Val Gly Arg Ser Ser Phe Tyr Cys Leu Glu Tyr Phe 385 390 395 400 Pro Ser Gln Met Leu Arg Thr Gly Asn Asn Phe Gln Phe Ser Tyr Glu 405 410 415 Phe Glu Asn Val Pro Phe His Ser Ser Tyr Ala His Ser Gln Ser Leu 420 425 430 Asp Arg Leu Met Asn Pro Leu Ile Asp Gln Tyr Leu Tyr Tyr Leu Ser 435 440 445 Lys Thr Ile Asn Gly Ser Gly Gln Asn Gln Gln Thr Leu Lys Phe Ser 450 455 460 Val Ala Gly Pro Ser Asn Met Ala Val Gln Gly Arg Asn Tyr Ile Pro 465 470 475 480 Gly Pro Ser Tyr Arg Gln Gln Arg Val Ser Thr Thr Val Thr Gln Asn 485 490 495 Asn Asn Ser Glu Phe Ala Trp Pro Gly Ala Ser Ser Trp Ala Leu Asn 500 505 510 Gly Arg Asn Ser Leu Met Asn Pro Gly Pro Ala Met Ala Ser His Lys 515 520 525 Glu Gly Glu Asp Arg Phe Phe Pro Leu Ser Gly Ser Leu Ile Phe Gly 530 535 540 Lys Gln Gly Thr Gly Arg Asp Asn Val Asp Ala Asp Lys Val Met Ile 545 550 555 560 Thr Asn Glu Glu Glu Ile Lys Thr Thr Asn Pro Val Ala Thr Glu Ser 565 570 575 Tyr Gly Gln Val Ala Thr Asn His Gln Ser Ala Gln Ala Gln Ala Gln 580 585 590 Thr Gly Trp Val Gln Asn Gln Gly Ile Leu Pro Gly Met Val Trp Gln 595 600 605 Asp Arg Asp Val Tyr Leu Gln Gly Pro Ile Trp Ala Lys Ile Pro His 610 615 620 Thr Asp Gly Asn Phe His Pro Ser Pro Leu Met Gly Gly Phe Gly Met 625 630 635 640 Lys His Pro Pro Pro Gln Ile Leu Ile Lys Asn Thr Pro Val Pro Ala 645 650 655 Asp Pro Pro Thr Ala Phe Asn Lys Asp Lys Leu Asn Ser Phe Ile Thr 660 665 670 Gln Tyr Ser Thr Gly Gln Val Ser Val Glu Ile Glu Trp Glu Leu Gln 675 680 685 Lys Glu Asn Ser Lys Arg Trp Asn Pro Glu Ile Gln Tyr Thr Ser Asn 690 695 700 Tyr Tyr Lys Ser Asn Asn Val Glu Phe Ala Val Asn Thr Glu Gly Val 705 710 715 720 Tyr Ser Glu Pro Arg Pro Ile Gly Thr Arg Tyr Leu Thr Arg Asn Leu 725 730 735 <210> SEQ ID NO 78 <211> LENGTH: 736 <212> TYPE: PRT <213> ORGANISM: Adeno-associated virus 6 <400> SEQUENCE: 78 Met Ala Ala Asp Gly Tyr Leu Pro Asp Trp Leu Glu Asp Asn Leu Ser 1 5 10 15 Glu Gly Ile Arg Glu Trp Trp Asp Leu Lys Pro Gly Ala Pro Lys Pro 20 25 30 Lys Ala Asn Gln Gln Lys Gln Asp Asp Gly Arg Gly Leu Val Leu Pro 35 40 45 Gly Tyr Lys Tyr Leu Gly Pro Phe Asn Gly Leu Asp Lys Gly Glu Pro 50 55 60 Val Asn Ala Ala Asp Ala Ala Ala Leu Glu His Asp Lys Ala Tyr Asp 65 70 75 80 Gln Gln Leu Lys Ala Gly Asp Asn Pro Tyr Leu Arg Tyr Asn His Ala 85 90 95 Asp Ala Glu Phe Gln Glu Arg Leu Gln Glu Asp Thr Ser Phe Gly Gly 100 105 110 Asn Leu Gly Arg Ala Val Phe Gln Ala Lys Lys Arg Val Leu Glu Pro 115 120 125 Phe Gly Leu Val Glu Glu Gly Ala Lys Thr Ala Pro Gly Lys Lys Arg 130 135 140 Pro Val Glu Gln Ser Pro Gln Glu Pro Asp Ser Ser Ser Gly Ile Gly 145 150 155 160 Lys Thr Gly Gln Gln Pro Ala Lys Lys Arg Leu Asn Phe Gly Gln Thr 165 170 175 Gly Asp Ser Glu Ser Val Pro Asp Pro Gln Pro Leu Gly Glu Pro Pro 180 185 190 Ala Thr Pro Ala Ala Val Gly Pro Thr Thr Met Ala Ser Gly Gly Gly 195 200 205 Ala Pro Met Ala Asp Asn Asn Glu Gly Ala Asp Gly Val Gly Asn Ala 210 215 220 Ser Gly Asn Trp His Cys Asp Ser Thr Trp Leu Gly Asp Arg Val Ile 225 230 235 240 Thr Thr Ser Thr Arg Thr Trp Ala Leu Pro Thr Tyr Asn Asn His Leu 245 250 255 Tyr Lys Gln Ile Ser Ser Ala Ser Thr Gly Ala Ser Asn Asp Asn His 260 265 270 Tyr Phe Gly Tyr Ser Thr Pro Trp Gly Tyr Phe Asp Phe Asn Arg Phe 275 280 285 His Cys His Phe Ser Pro Arg Asp Trp Gln Arg Leu Ile Asn Asn Asn 290 295 300 Trp Gly Phe Arg Pro Lys Arg Leu Asn Phe Lys Leu Phe Asn Ile Gln 305 310 315 320 Val Lys Glu Val Thr Thr Asn Asp Gly Val Thr Thr Ile Ala Asn Asn 325 330 335 Leu Thr Ser Thr Val Gln Val Phe Ser Asp Ser Glu Tyr Gln Leu Pro 340 345 350 Tyr Val Leu Gly Ser Ala His Gln Gly Cys Leu Pro Pro Phe Pro Ala 355 360 365 Asp Val Phe Met Ile Pro Gln Tyr Gly Tyr Leu Thr Leu Asn Asn Gly 370 375 380 Ser Gln Ala Val Gly Arg Ser Ser Phe Tyr Cys Leu Glu Tyr Phe Pro 385 390 395 400 Ser Gln Met Leu Arg Thr Gly Asn Asn Phe Thr Phe Ser Tyr Thr Phe 405 410 415 Glu Asp Val Pro Phe His Ser Ser Tyr Ala His Ser Gln Ser Leu Asp 420 425 430 Arg Leu Met Asn Pro Leu Ile Asp Gln Tyr Leu Tyr Tyr Leu Asn Arg 435 440 445 Thr Gln Asn Gln Ser Gly Ser Ala Gln Asn Lys Asp Leu Leu Phe Ser 450 455 460 Arg Gly Ser Pro Ala Gly Met Ser Val Gln Pro Lys Asn Trp Leu Pro 465 470 475 480 Gly Pro Cys Tyr Arg Gln Gln Arg Val Ser Lys Thr Lys Thr Asp Asn 485 490 495 Asn Asn Ser Asn Phe Thr Trp Thr Gly Ala Ser Lys Tyr Asn Leu Asn 500 505 510 Gly Arg Glu Ser Ile Ile Asn Pro Gly Thr Ala Met Ala Ser His Lys 515 520 525 Asp Asp Lys Asp Lys Phe Phe Pro Met Ser Gly Val Met Ile Phe Gly 530 535 540 Lys Glu Ser Ala Gly Ala Ser Asn Thr Ala Leu Asp Asn Val Met Ile 545 550 555 560 Thr Asp Glu Glu Glu Ile Lys Ala Thr Asn Pro Val Ala Thr Glu Arg 565 570 575 Phe Gly Thr Val Ala Val Asn Leu Gln Ser Ser Ser Thr Asp Pro Ala 580 585 590 Thr Gly Asp Val His Val Met Gly Ala Leu Pro Gly Met Val Trp Gln 595 600 605 Asp Arg Asp Val Tyr Leu Gln Gly Pro Ile Trp Ala Lys Ile Pro His 610 615 620 Thr Asp Gly His Phe His Pro Ser Pro Leu Met Gly Gly Phe Gly Leu 625 630 635 640 Lys His Pro Pro Pro Gln Ile Leu Ile Lys Asn Thr Pro Val Pro Ala 645 650 655 Asn Pro Pro Ala Glu Phe Ser Ala Thr Lys Phe Ala Ser Phe Ile Thr 660 665 670 Gln Tyr Ser Thr Gly Gln Val Ser Val Glu Ile Glu Trp Glu Leu Gln 675 680 685 Lys Glu Asn Ser Lys Arg Trp Asn Pro Glu Val Gln Tyr Thr Ser Asn 690 695 700 Tyr Ala Lys Ser Ala Asn Val Asp Phe Thr Val Asp Asn Asn Gly Leu 705 710 715 720 Tyr Thr Glu Pro Arg Pro Ile Gly Thr Arg Tyr Leu Thr Arg Pro Leu 725 730 735 <210> SEQ ID NO 79 <211> LENGTH: 738 <212> TYPE: PRT <213> ORGANISM: Non-human primate Adeno-associated virus <400> SEQUENCE: 79 Met Ala Ala Asp Gly Tyr Leu Pro Asp Trp Leu Glu Asp Asn Leu Ser 1 5 10 15 Glu Gly Ile Arg Glu Trp Trp Asp Leu Lys Pro Gly Ala Pro Lys Pro 20 25 30 Lys Ala Asn Gln Gln Lys Gln Asp Asp Gly Arg Gly Leu Val Leu Pro 35 40 45 Gly Tyr Lys Tyr Leu Gly Pro Phe Asn Gly Leu Asp Lys Gly Glu Pro 50 55 60 Val Asn Ala Ala Asp Ala Ala Ala Leu Glu His Asp Lys Ala Tyr Asp 65 70 75 80 Gln Gln Leu Lys Ala Gly Asp Asn Pro Tyr Leu Arg Tyr Asn His Ala 85 90 95 Asp Ala Glu Phe Gln Glu Arg Leu Gln Glu Asp Thr Ser Phe Gly Gly 100 105 110 Asn Leu Gly Arg Ala Val Phe Gln Ala Lys Lys Arg Val Leu Glu Pro 115 120 125 Leu Gly Leu Val Glu Glu Gly Ala Lys Thr Ala Pro Gly Lys Lys Arg 130 135 140 Pro Val Glu Pro Ser Pro Gln Arg Ser Pro Asp Ser Ser Thr Gly Ile 145 150 155 160 Gly Lys Lys Gly Gln Gln Pro Ala Lys Lys Arg Leu Asn Phe Gly Gln 165 170 175 Thr Gly Asp Ser Glu Ser Val Pro Asp Pro Gln Pro Ile Gly Glu Pro 180 185 190 Pro Ala Gly Pro Ser Gly Leu Gly Ser Gly Thr Met Ala Ala Gly Gly 195 200 205 Gly Ala Pro Met Ala Asp Asn Asn Glu Gly Ala Asp Gly Val Gly Ser 210 215 220 Ser Ser Gly Asn Trp His Cys Asp Ser Thr Trp Leu Gly Asp Arg Val 225 230 235 240 Ile Thr Thr Ser Thr Arg Thr Trp Ala Leu Pro Thr Tyr Asn Asn His 245 250 255 Leu Tyr Lys Gln Ile Ser Asn Gly Thr Ser Gly Gly Ser Thr Asn Asp 260 265 270 Asn Thr Tyr Phe Gly Tyr Ser Thr Pro Trp Gly Tyr Phe Asp Phe Asn 275 280 285 Arg Phe His Cys His Phe Ser Pro Arg Asp Trp Gln Arg Leu Ile Asn 290 295 300 Asn Asn Trp Gly Phe Arg Pro Lys Arg Leu Asn Phe Lys Leu Phe Asn 305 310 315 320 Ile Gln Val Lys Glu Val Thr Gln Asn Glu Gly Thr Lys Thr Ile Ala 325 330 335 Asn Asn Leu Thr Ser Thr Ile Gln Val Phe Thr Asp Ser Glu Tyr Gln 340 345 350 Leu Pro Tyr Val Leu Gly Ser Ala His Gln Gly Cys Leu Pro Pro Phe 355 360 365 Pro Ala Asp Val Phe Met Ile Pro Gln Tyr Gly Tyr Leu Thr Leu Asn 370 375 380 Asn Gly Ser Gln Ala Val Gly Arg Ser Ser Phe Tyr Cys Leu Glu Tyr 385 390 395 400 Phe Pro Ser Gln Met Leu Arg Thr Gly Asn Asn Phe Glu Phe Ser Tyr 405 410 415 Gln Phe Glu Asp Val Pro Phe His Ser Ser Tyr Ala His Ser Gln Ser 420 425 430 Leu Asp Arg Leu Met Asn Pro Leu Ile Asp Gln Tyr Leu Tyr Tyr Leu 435 440 445 Ser Arg Thr Gln Ser Thr Gly Gly Thr Ala Gly Thr Gln Gln Leu Leu 450 455 460 Phe Ser Gln Ala Gly Pro Asn Asn Met Ser Ala Gln Ala Lys Asn Trp 465 470 475 480 Leu Pro Gly Pro Cys Tyr Arg Gln Gln Arg Val Ser Thr Thr Leu Ser 485 490 495 Gln Asn Asn Asn Ser Asn Phe Ala Trp Thr Gly Ala Thr Lys Tyr His 500 505 510 Leu Asn Gly Arg Asp Ser Leu Val Asn Pro Gly Val Ala Met Ala Thr 515 520 525 His Lys Asp Asp Glu Glu Arg Phe Phe Pro Ser Ser Gly Val Leu Met 530 535 540 Phe Gly Lys Gln Gly Ala Gly Lys Asp Asn Val Asp Tyr Ser Ser Val 545 550 555 560 Met Leu Thr Ser Glu Glu Glu Ile Lys Thr Thr Asn Pro Val Ala Thr 565 570 575 Glu Gln Tyr Gly Val Val Ala Asp Asn Leu Gln Gln Gln Asn Ala Ala 580 585 590 Pro Ile Val Gly Ala Val Asn Ser Gln Gly Ala Leu Pro Gly Met Val 595 600 605 Trp Gln Asn Arg Asp Val Tyr Leu Gln Gly Pro Ile Trp Ala Lys Ile 610 615 620 Pro His Thr Asp Gly Asn Phe His Pro Ser Pro Leu Met Gly Gly Phe 625 630 635 640 Gly Leu Lys His Pro Pro Pro Gln Ile Leu Ile Lys Asn Thr Pro Val 645 650 655 Pro Ala Asp Pro Pro Thr Thr Phe Ser Gln Ala Lys Leu Ala Ser Phe 660 665 670 Ile Thr Gln Tyr Ser Thr Gly Gln Val Ser Val Glu Ile Glu Trp Glu 675 680 685 Leu Gln Lys Glu Asn Ser Lys Arg Trp Asn Pro Glu Ile Gln Tyr Thr 690 695 700 Ser Asn Tyr Tyr Lys Ser Thr Asn Val Asp Phe Ala Val Asn Thr Asp 705 710 715 720 Gly Thr Tyr Ser Glu Pro Arg Pro Ile Gly Thr Arg Tyr Leu Thr Arg 725 730 735 Asn Leu <210> SEQ ID NO 80 <211> LENGTH: 2217 <212> TYPE: DNA <213> ORGANISM: Non-human primate adeno-associated virus <400> SEQUENCE: 80 atggctgccg atggttatct tccagattgg ctcgaggaca acctctctga gggcattcgc 60 gagtggtggg acctgaaacc tggagccccg aaacccaaag ccaaccagca aaagcaggac 120 aacggccggg gtctggtgct tcctggctac aagtacctcg gacccttcaa cggactcgac 180 aagggggagc ccgtcaacgc ggcggacgca gcggccctcg agcacgacaa ggcctacgac 240 cagcagctcc aagcgggtga caatccgtac ctgcggtata atcacgccga cgccgagttt 300 caggagcgtc tgcaagaaga tacgtctttt gggggcaacc tcgggcgcgc agtcttccag 360 gccaaaaagc gggttctcga acctctgggc ctggttgaat cgccggttaa gacggctcct 420 ggaaagaaga gaccggtaga gccatcaccc cagcgctctc cagactcctc tacgggcatc 480 ggcaagaaag gccagcagcc cgcaaaaaag agactcaatt ttgggcagac tggcgactca 540 gagtcagtcc ccgaccctca accaatcgga gaaccaccag caggcccctc tggtctggga 600 tctggtacaa tggctgcagg cggtggcgct ccaatggcag acaataacga aggcgccgac 660 ggagtgggta gttcctcagg aaattggcat tgcgattcca catggctggg cgacagagtc 720 atcaccacca gcacccgcac ctgggccctg cccacctaca acaaccacct ctacaagcaa 780 atctccaacg ggacctcggg aggaagcacc aacgacaaca cctacttcgg ctacagcacc 840 ccctgggggt attttgactt caacagattc cactgccact tttcaccacg tgactggcag 900 cgactcatca acaacaactg gggattccgg cccaagaggc tcaacttcaa gctcttcaac 960 atccaagtca aggaggtcac gcagaatgaa ggcaccaaga ccatcgccaa taaccttacc 1020 agcacgattc aggtctttac ggactcggaa taccagctcc cgtacgtgct cggctcggcg 1080 caccagggct gcctgcctcc gttcccggcg gacgtcttca tgattcctca gtacgggtac 1140 ctgactctga acaatggcag tcaggctgtg ggccggtcgt ccttctactg cctggagtac 1200 tttccttctc aaatgctgag aacgggcaac aactttgaat tcagctacaa cttcgaggac 1260 gtgcccttcc acagcagcta cgcgcacagc cagagcctgg accggctgat gaaccctctc 1320 atcgaccagt acttgtacta cctgtcccgg actcaaagca cgggcggtac tgcaggaact 1380 cagcagttgc tattttctca ggccgggcct aacaacatgt cggctcaggc caagaactgg 1440 ctacccggtc cctgctaccg gcagcaacgc gtctccacga cactgtcgca gaacaacaac 1500 agcaactttg cctggacggg tgccaccaag tatcatctga atggcagaga ctctctggtg 1560 aatcctggcg ttgccatggc tacccacaag gacgacgaag agcgattttt tccatccagc 1620 ggagtcttaa tgtttgggaa acagggagct ggaaaagaca acgtggacta tagcagcgtg 1680 atgctaacca gcgaggaaga aataaagacc accaacccag tggccacaga acagtacggc 1740 gtggtggccg ataacctgca acagcaaaac gccgctccta ttgtaggggc cgtcaatagt 1800 caaggagcct tacctggcat ggtgtggcag aaccgggacg tgtacctgca gggtcccatc 1860 tgggccaaga ttcctcatac ggacggcaac tttcatccct cgccgctgat gggaggcttt 1920 ggactgaagc atccgcctcc tcagatcctg attaaaaaca cacctgttcc cgcggatcct 1980 ccgaccacct tcaatcaggc caagctggct tctttcatca cgcagtacag taccggccag 2040 gtcagcgtgg agatcgagtg ggagctgcag aaggagaaca gcaaacgctg gaacccagag 2100 attcagtaca cttccaacta ctacaaatct acaaatgtgg actttgctgt caatactgag 2160 ggtacttatt ccgagcctcg ccccattggc acccgttacc tcacccgtaa tctgtaa 2217 <210> SEQ ID NO 81 <211> LENGTH: 535 <212> TYPE: PRT <213> ORGANISM: Non-human primate adeno-associated virus <400> SEQUENCE: 81 Met Ala Ala Gly Gly Gly Ala Pro Met Ala Asp Asn Asn Glu Gly Ala 1 5 10 15 Asp Gly Val Gly Ser Ser Ser Gly Asn Trp His Cys Asp Ser Thr Trp 20 25 30 Leu Gly Asp Arg Val Ile Thr Thr Ser Thr Arg Thr Trp Ala Leu Pro 35 40 45 Thr Tyr Asn Asn His Leu Tyr Lys Gln Ile Ser Asn Gly Thr Ser Gly 50 55 60 Gly Ser Thr Asn Asp Asn Thr Tyr Phe Gly Tyr Ser Thr Pro Trp Gly 65 70 75 80 Tyr Phe Asp Phe Asn Arg Phe His Cys His Phe Ser Pro Arg Asp Trp 85 90 95 Gln Arg Leu Ile Asn Asn Asn Trp Gly Phe Arg Pro Lys Arg Leu Asn 100 105 110 Phe Lys Leu Phe Asn Ile Gln Val Lys Glu Val Thr Gln Asn Glu Gly 115 120 125 Thr Lys Thr Ile Ala Asn Asn Leu Thr Ser Thr Ile Gln Val Phe Thr 130 135 140 Asp Ser Glu Tyr Gln Leu Pro Tyr Val Leu Gly Ser Ala His Gln Gly 145 150 155 160 Cys Leu Pro Pro Phe Pro Ala Asp Val Phe Met Ile Pro Gln Tyr Gly 165 170 175 Tyr Leu Thr Leu Asn Asn Gly Ser Gln Ala Val Gly Arg Ser Ser Phe 180 185 190 Tyr Cys Leu Glu Tyr Phe Pro Ser Gln Met Leu Arg Thr Gly Asn Asn 195 200 205 Phe Glu Phe Ser Tyr Asn Phe Glu Asp Val Pro Phe His Ser Ser Tyr 210 215 220 Ala His Ser Gln Ser Leu Asp Arg Leu Met Asn Pro Leu Ile Asp Gln 225 230 235 240 Tyr Leu Tyr Tyr Leu Ser Arg Thr Gln Ser Thr Gly Gly Thr Ala Gly 245 250 255 Thr Gln Gln Leu Leu Phe Ser Gln Ala Gly Pro Asn Asn Met Ser Ala 260 265 270 Gln Ala Lys Asn Trp Leu Pro Gly Pro Cys Tyr Arg Gln Gln Arg Val 275 280 285 Ser Thr Thr Leu Ser Gln Asn Asn Asn Ser Asn Phe Ala Trp Thr Gly 290 295 300 Ala Thr Lys Tyr His Leu Asn Gly Arg Asp Ser Leu Val Asn Pro Gly 305 310 315 320 Val Ala Met Ala Thr His Lys Asp Asp Glu Glu Arg Phe Phe Pro Ser 325 330 335 Ser Gly Val Leu Met Phe Gly Lys Gln Gly Ala Gly Lys Asp Asn Val 340 345 350 Asp Tyr Ser Ser Val Met Leu Thr Ser Glu Glu Glu Ile Lys Thr Thr 355 360 365 Asn Pro Val Ala Thr Glu Gln Tyr Gly Val Val Ala Asp Asn Leu Gln 370 375 380 Gln Gln Asn Ala Ala Pro Ile Val Gly Ala Val Asn Ser Gln Gly Ala 385 390 395 400 Leu Pro Gly Met Val Trp Gln Asn Arg Asp Val Tyr Leu Gln Gly Pro 405 410 415 Ile Trp Ala Lys Ile Pro His Thr Asp Gly Asn Phe His Pro Ser Pro 420 425 430 Leu Met Gly Gly Phe Gly Leu Lys His Pro Pro Pro Gln Ile Leu Ile 435 440 445 Lys Asn Thr Pro Val Pro Ala Asp Pro Pro Thr Thr Phe Asn Gln Ala 450 455 460 Lys Leu Ala Ser Phe Ile Thr Gln Tyr Ser Thr Gly Gln Val Ser Val 465 470 475 480 Glu Ile Glu Trp Glu Leu Gln Lys Glu Asn Ser Lys Arg Trp Asn Pro 485 490 495 Glu Ile Gln Tyr Thr Ser Asn Tyr Tyr Lys Ser Thr Asn Val Asp Phe 500 505 510 Ala Val Asn Thr Glu Gly Thr Tyr Ser Glu Pro Arg Pro Ile Gly Thr 515 520 525 Arg Tyr Leu Thr Arg Asn Leu 530 535 <210> SEQ ID NO 82 <211> LENGTH: 398 <212> TYPE: PRT <213> ORGANISM: Non-human primate adeno-associated virus <400> SEQUENCE: 82 Ser Thr Ile Gln Val Phe Thr Asp Ser Glu Tyr Gln Leu Pro Tyr Val 1 5 10 15 Leu Gly Ser Ala His Gln Gly Cys Leu Pro Pro Phe Pro Ala Asp Val 20 25 30 Phe Met Ile Pro Gln Tyr Gly Tyr Leu Thr Leu Asn Asn Gly Ser Gln 35 40 45 Ala Val Gly Arg Ser Ser Phe Tyr Cys Leu Glu Tyr Phe Pro Ser Gln 50 55 60 Met Leu Arg Thr Gly Asn Asn Phe Glu Phe Ser Tyr Asn Phe Glu Asp 65 70 75 80 Val Pro Phe His Ser Ser Tyr Ala His Ser Gln Ser Leu Asp Arg Leu 85 90 95 Met Asn Pro Leu Ile Asp Gln Tyr Leu Tyr Tyr Leu Ser Arg Thr Gln 100 105 110 Ser Thr Gly Gly Thr Ala Gly Thr Gln Gln Leu Leu Phe Ser Gln Ala 115 120 125 Gly Pro Asn Asn Met Ser Ala Gln Ala Lys Asn Trp Leu Pro Gly Pro 130 135 140 Cys Tyr Arg Gln Gln Arg Val Ser Thr Thr Leu Ser Gln Asn Asn Asn 145 150 155 160 Ser Asn Phe Ala Trp Thr Gly Ala Thr Lys Tyr His Leu Asn Gly Arg 165 170 175 Asp Ser Leu Val Asn Pro Gly Val Ala Met Ala Thr His Lys Asp Asp 180 185 190 Glu Glu Arg Phe Phe Pro Ser Ser Gly Val Leu Met Phe Gly Lys Gln 195 200 205 Gly Ala Gly Lys Asp Asn Val Asp Tyr Ser Ser Val Met Leu Thr Ser 210 215 220 Glu Glu Glu Ile Lys Thr Thr Asn Pro Val Ala Thr Glu Gln Tyr Gly 225 230 235 240 Val Val Ala Asp Asn Leu Gln Gln Gln Asn Ala Ala Pro Ile Val Gly 245 250 255 Ala Val Asn Ser Gln Gly Ala Leu Pro Gly Met Val Trp Gln Asn Arg 260 265 270 Asp Val Tyr Leu Gln Gly Pro Ile Trp Ala Lys Ile Pro His Thr Asp 275 280 285 Gly Asn Phe His Pro Ser Pro Leu Met Gly Gly Phe Gly Leu Lys His 290 295 300 Pro Pro Pro Gln Ile Leu Ile Lys Asn Thr Pro Val Pro Ala Asp Pro 305 310 315 320 Pro Thr Thr Phe Asn Gln Ala Lys Leu Ala Ser Phe Ile Thr Gln Tyr 325 330 335 Ser Thr Gly Gln Val Ser Val Glu Ile Glu Trp Glu Leu Gln Lys Glu 340 345 350 Asn Ser Lys Arg Trp Asn Pro Glu Ile Gln Tyr Thr Ser Asn Tyr Tyr 355 360 365 Lys Ser Thr Asn Val Asp Phe Ala Val Asn Thr Glu Gly Thr Tyr Ser 370 375 380 Glu Pro Arg Pro Ile Gly Thr Arg Tyr Leu Thr Arg Asn Leu 385 390 395 <210> SEQ ID NO 83 <211> LENGTH: 332 <212> TYPE: PRT <213> ORGANISM: Non-human primate adeno-associated virus <400> SEQUENCE: 83 Arg Thr Gly Asn Asn Phe Glu Phe Ser Tyr Asn Phe Glu Asp Val Pro 1 5 10 15 Phe His Ser Ser Tyr Ala His Ser Gln Ser Leu Asp Arg Leu Met Asn 20 25 30 Pro Leu Ile Asp Gln Tyr Leu Tyr Tyr Leu Ser Arg Thr Gln Ser Thr 35 40 45 Gly Gly Thr Ala Gly Thr Gln Gln Leu Leu Phe Ser Gln Ala Gly Pro 50 55 60 Asn Asn Met Ser Ala Gln Ala Lys Asn Trp Leu Pro Gly Pro Cys Tyr 65 70 75 80 Arg Gln Gln Arg Val Ser Thr Thr Leu Ser Gln Asn Asn Asn Ser Asn 85 90 95 Phe Ala Trp Thr Gly Ala Thr Lys Tyr His Leu Asn Gly Arg Asp Ser 100 105 110 Leu Val Asn Pro Gly Val Ala Met Ala Thr His Lys Asp Asp Glu Glu 115 120 125 Arg Phe Phe Pro Ser Ser Gly Val Leu Met Phe Gly Lys Gln Gly Ala 130 135 140 Gly Lys Asp Asn Val Asp Tyr Ser Ser Val Met Leu Thr Ser Glu Glu 145 150 155 160 Glu Ile Lys Thr Thr Asn Pro Val Ala Thr Glu Gln Tyr Gly Val Val 165 170 175 Ala Asp Asn Leu Gln Gln Gln Asn Ala Ala Pro Ile Val Gly Ala Val 180 185 190 Asn Ser Gln Gly Ala Leu Pro Gly Met Val Trp Gln Asn Arg Asp Val 195 200 205 Tyr Leu Gln Gly Pro Ile Trp Ala Lys Ile Pro His Thr Asp Gly Asn 210 215 220 Phe His Pro Ser Pro Leu Met Gly Gly Phe Gly Leu Lys His Pro Pro 225 230 235 240 Pro Gln Ile Leu Ile Lys Asn Thr Pro Val Pro Ala Asp Pro Pro Thr 245 250 255 Thr Phe Asn Gln Ala Lys Leu Ala Ser Phe Ile Thr Gln Tyr Ser Thr 260 265 270 Gly Gln Val Ser Val Glu Ile Glu Trp Glu Leu Gln Lys Glu Asn Ser 275 280 285 Lys Arg Trp Asn Pro Glu Ile Gln Tyr Thr Ser Asn Tyr Tyr Lys Ser 290 295 300 Thr Asn Val Asp Phe Ala Val Asn Thr Glu Gly Thr Tyr Ser Glu Pro 305 310 315 320 Arg Pro Ile Gly Thr Arg Tyr Leu Thr Arg Asn Leu 325 330 <210> SEQ ID NO 84 <211> LENGTH: 743 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic construct - AAV9 variant <400> SEQUENCE: 84 Met Ala Ala Asp Gly Tyr Leu Pro Asp Trp Leu Glu Asp Asn Leu Ser 1 5 10 15 Glu Gly Ile Arg Glu Trp Trp Ala Leu Lys Pro Gly Ala Pro Gln Pro 20 25 30 Lys Ala Asn Gln Gln His Gln Asp Asn Ala Arg Gly Leu Val Leu Pro 35 40 45 Gly Tyr Lys Tyr Leu Gly Pro Gly Asn Gly Leu Asp Lys Gly Glu Pro 50 55 60 Val Asn Ala Ala Asp Ala Ala Ala Leu Glu His Asp Lys Ala Tyr Asp 65 70 75 80 Gln Gln Leu Lys Ala Gly Asp Asn Pro Tyr Leu Lys Tyr Asn His Ala 85 90 95 Asp Ala Glu Phe Gln Glu Arg Leu Lys Glu Asp Thr Ser Phe Gly Gly 100 105 110 Asn Leu Gly Arg Ala Val Phe Gln Ala Lys Lys Arg Leu Leu Glu Pro 115 120 125 Leu Gly Leu Val Glu Glu Ala Ala Lys Thr Ala Pro Gly Lys Lys Arg 130 135 140 Pro Val Glu Gln Ser Pro Gln Glu Pro Asp Ser Ser Ala Gly Ile Gly 145 150 155 160 Lys Ser Gly Ala Gln Pro Ala Lys Lys Arg Leu Asn Phe Gly Gln Thr 165 170 175 Gly Asp Thr Glu Ser Val Pro Asp Pro Gln Pro Ile Gly Glu Pro Pro 180 185 190 Ala Ala Pro Ser Gly Val Gly Ser Leu Thr Met Ala Ser Gly Gly Gly 195 200 205 Ala Pro Val Ala Asp Asn Asn Glu Gly Ala Asp Gly Val Gly Ser Ser 210 215 220 Ser Gly Asn Trp His Cys Asp Ser Gln Trp Leu Gly Asp Arg Val Ile 225 230 235 240 Thr Thr Ser Thr Arg Thr Trp Ala Leu Pro Thr Tyr Asn Asn His Leu 245 250 255 Tyr Lys Gln Ile Ser Asn Ser Thr Ser Gly Gly Ser Ser Asn Asp Asn 260 265 270 Ala Tyr Phe Gly Tyr Ser Thr Pro Trp Gly Tyr Phe Asp Phe Asn Arg 275 280 285 Phe His Cys His Phe Ser Pro Arg Asp Trp Gln Arg Leu Ile Asn Asn 290 295 300 Asn Trp Gly Phe Arg Pro Lys Arg Leu Asn Phe Lys Leu Phe Asn Ile 305 310 315 320 Gln Val Lys Glu Val Thr Asp Asn Asn Gly Val Lys Thr Ile Ala Asn 325 330 335 Asn Leu Thr Ser Thr Val Gln Val Phe Thr Asp Ser Asp Tyr Gln Leu 340 345 350 Pro Tyr Val Leu Gly Ser Ala His Glu Gly Cys Leu Pro Pro Phe Pro 355 360 365 Ala Asp Val Phe Met Ile Pro Gln Tyr Gly Tyr Leu Thr Leu Asn Asp 370 375 380 Gly Ser Gln Ala Val Gly Arg Ser Ser Phe Tyr Cys Leu Glu Tyr Phe 385 390 395 400 Pro Ser Gln Met Leu Arg Thr Gly Asn Asn Phe Gln Phe Ser Tyr Glu 405 410 415 Phe Glu Asn Val Pro Phe His Ser Ser Tyr Ala His Ser Gln Ser Leu 420 425 430 Asp Arg Leu Met Asn Pro Leu Ile Asp Gln Tyr Leu Tyr Tyr Leu Ser 435 440 445 Arg Thr Ile Asn Gly Ser Gly Gln Asn Gln Gln Thr Leu Lys Phe Ser 450 455 460 Val Ala Gly Pro Ser Asn Met Ala Val Gln Gly Arg Asn Tyr Ile Pro 465 470 475 480 Gly Pro Ser Tyr Arg Gln Gln Arg Val Ser Thr Thr Val Thr Gln Asn 485 490 495 Asn Asn Ser Glu Phe Ala Trp Pro Gly Ala Ser Ser Trp Ala Leu Asn 500 505 510 Gly Arg Asn Ser Leu Met Asn Pro Gly Pro Ala Met Ala Ser His Lys 515 520 525 Glu Gly Glu Asp Arg Phe Phe Pro Leu Ser Gly Ser Leu Ile Phe Gly 530 535 540 Lys Gln Gly Thr Gly Arg Asp Asn Val Asp Ala Asp Lys Val Met Ile 545 550 555 560 Thr Asn Glu Glu Glu Ile Lys Thr Thr Asn Pro Val Ala Thr Glu Ser 565 570 575 Tyr Gly Gln Val Ala Thr Asn His Gln Ser Ala Gln Thr Leu Ala Val 580 585 590 Pro Phe Lys Ala Gln Ala Gln Thr Gly Trp Val Gln Asn Gln Gly Ile 595 600 605 Leu Pro Gly Met Val Trp Gln Asp Arg Asp Val Tyr Leu Gln Gly Pro 610 615 620 Ile Trp Ala Lys Ile Pro His Thr Asp Gly Asn Phe His Pro Ser Pro 625 630 635 640 Leu Met Gly Gly Phe Gly Met Lys His Pro Pro Pro Gln Ile Leu Ile 645 650 655 Lys Asn Thr Pro Val Pro Ala Asp Pro Pro Thr Ala Phe Asn Lys Asp 660 665 670 Lys Leu Asn Ser Phe Ile Thr Gln Tyr Ser Thr Gly Gln Val Ser Val 675 680 685 Glu Ile Glu Trp Glu Leu Gln Lys Glu Asn Ser Lys Arg Trp Asn Pro 690 695 700 Glu Ile Gln Tyr Thr Ser Asn Tyr Tyr Lys Ser Asn Asn Val Glu Phe 705 710 715 720 Ala Val Asn Thr Glu Gly Val Tyr Ser Glu Pro Arg Pro Ile Gly Thr 725 730 735 Arg Tyr Leu Thr Arg Asn Leu 740 <210> SEQ ID NO 85 <211> LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Peptide insert <400> SEQUENCE: 85 Thr Leu Ala Val Pro Phe Lys 1 5 <210> SEQ ID NO 86 <211> LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Peptide insert <400> SEQUENCE: 86 Lys Phe Pro Val Ala Leu Thr 1 5 <210> SEQ ID NO 87 <211> LENGTH: 2514 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Made in Lab - codon optimized PKP2a polynucleotide <400> SEQUENCE: 87 atggctgcac ctggtgcgcc tgccgaatat ggttatataa ggacagtttt gggtcaacag 60 atacttggac aacttgattc ctcttctttg gcgctccctt cagaagcaaa gttgaaattg 120 gcaggttcat caggtagagg aggacaaact gtgaaatctc tgcggattca ggaacaagta 180 caacagactt tggctagaaa gggaagatct tccgttggca atggaaattt gcatagaacg 240 agcagcgtac ctgaatacgt atacaatctc catcttgttg aaaacgattt tgtaggaggt 300 cggtctccag ttccgaaaac atatgatatg cttaaagcag gtactacagc tacatacgaa 360 ggtagatggg gaagaggaac tgcacaatat tcatctcaaa aatctgttga agaaaggtca 420 ttgcgacatc ctctcagaag gctcgaaatt tccccggatt catcacctga aagggctcat 480 tatacacaca gtgattatca atatagccaa cgatctcaag caggtcatac acttcatcat 540 caggaaagta ggcgggcggc attgcttgta ccccctcgat atgccaggtc agaaattgta 600 ggagtttcca gagcaggtac tactagtcga caaagacact ttgacacata tcataggcaa 660 tatcaacacg gtagtgtctc agacactgtt tttgattcaa taccagcaaa tccggcattg 720 ctgacgtatc ctcgacctgg tacgtcaagg agcatgggaa atcttctgga gaaagaaaat 780 tatttgactg ctgggcttac agttggacag gtacggccat tggttcctct tcaaccagtt 840 actcagaatc gagcttccag aagctcttgg catcaatcaa gctttcattc cacaaggaca 900 ctgagagaag caggaccttc tgttgccgtt gattccagtg ggcggagagc ccaccttaca 960 gtaggtcaag cagctgccgg aggatcaggt aatttgctta cagaaaggag tacttttaca 1020 gatagccaac tcgggaatgc ggatatggaa atgacattgg agagagctgt atcaatgctg 1080 gaagcggatc atatgcttcc ttctagaatt tccgctgcgg caacttttat acagcacgaa 1140 tgttttcaaa aatccgaagc gcgaaagcgg gttaatcagc tgagaggtat tctgaaactg 1200 ttgcaacttt tgaaagtgca aaatgaagat gttcaaagag ctgtttgtgg agctcttaga 1260 aatcttgttt ttgaagataa tgataataaa ttggaagttg ctgaacttaa tggtgtacct 1320 agattgcttc aagttttgaa acaaacaaga gatttggaaa caaaaaaaca aataacagga 1380 cttttgtgga atctttcttc taatgataaa cttaaaaatt tgatgataac agaagctttg 1440 ttgacactta cagaaaatat tattatacct ttttctggat ggcctgaagg ggattatcca 1500 aaagctaatg ggttgctgga ttttgatatt ttttataatg tgacaggatg tttgaggaat 1560 atgtcctcag ctggtgctga cggtcggaaa gcaatgaggc gatgtgacgg tttgatcgat 1620 tcccttgttc attacgttag gggaacaata gctgattatc aaccagatga taaagcaaca 1680 gaaaattgtg tttgtattct tcataatctg tcttatcaat tggaagccga acttcctgaa 1740 aaatactctc aaaatatcta tattcagaat cggaacatac aaactgataa taacaaatct 1800 ataggatgtt ttggatcaag aagcagaaaa gttaaggaac aatatcaaga cgttcctatg 1860 cccgaagaaa aatcaaatcc aaagggtgta gaatggctgt ggcattctat tgttattaga 1920 atgtatttgt cactcatagc aaaatctgta cgaaattata cacaagaagc ttctttggga 1980 gcccttcaga atcttacagc aggaagtggt cctatgccta caagtgtagc gcaaacagtt 2040 gtacagaaag aatctggatt gcaacatact agaaagatgc tgcatgtagg agatccttct 2100 gttaaaaaga cagctataag cctcctgagg aacttgagtc gcaacttgtc tctccagaat 2160 gagattgcta aggaaacgct tcctgacctt gtatctatta tacctgacac ggtgccttcc 2220 acagatcttt tgattgaaac aactgcatct gcttgttata cattgaataa tatcattcaa 2280 aatagttatc agaacgcaag agatcttctg aatacaggag gtattcaaaa aataatggct 2340 atttcagcag gtgatgcata tgcttctaat aaagcgtcta aagctgcatc tgttcttttg 2400 tattctcttt gggcacatac agaacttcac catgcctaca agaaagctca attcaagaaa 2460 acagattttg ttaatagtcg cactgcaaaa gcgtatcatt cccttaagga ttaa 2514 <210> SEQ ID NO 88 <211> LENGTH: 2646 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Made in Lab - codon optimized PKP2b polynucleotide <400> SEQUENCE: 88 atggccgcac ctggagctcc agctgaatat ggatatatca ggactgtctt gggtcagcag 60 attctgggcc aactggattc ttcaagtctg gccctcccga gtgaggcaaa actgaaactc 120 gcaggatcta gtggaagggg cggacagaca gtgaagtcac tcaggattca ggagcaggtc 180 caacagacac tggcaagaaa agggaggtcc agcgtcggca atggtaactt gcatagaacc 240 tcttcagtgc ctgagtacgt gtacaacctg cacctggtgg aaaacgattt tgtgggcggc 300 agatccccgg tccctaaaac ttatgacatg ctgaaagctg gcacgacagc tacatatgaa 360 ggtagatggg gccggggcac cgcacaatat agttctcaga agtccgtgga agaaagatct 420 cttaggcacc cacttcggcg actggagata agtccagaca gcagccccga aagggcgcat 480 tatacacatt ctgactacca atacagccaa agatctcagg ctggccacac tctgcatcat 540 caggaaagta gaagggccgc ccttctcgtc cccccaagat acgcacggtc agaaatcgtg 600 ggagtgagca gagcaggtac cacctctcga cagaggcatt tcgacacata ccaccgacaa 660 taccaacatg gatcagtgtc agatactgtt tttgactcca taccagcaaa tccagcactc 720 ctgacatatc ctagaccggg gactagtcgc tccatgggga atctgctcga aaaagaaaac 780 tatctcaccg caggtctgac tgtggggcag gtaaggccgt tggtgcccct tcagcctgta 840 acgcagaata gggcttccag gtcatcctgg caccagagta gcttccactc cacaaggact 900 ctgagagagg caggccctag tgttgcagtt gatagttccg gtcgcagggc ccatcttaca 960 gttggtcaag ccgctgcagg gggtagcggt aatctgctga ccgaaagaag cacattcacg 1020 gattcccagc tcggaaatgc agacatggag atgacacttg aacgagccgt gagcatgctg 1080 gaagctgacc atatgctccc ttctagaatc tccgctgcgg ccactttcat ccagcacgag 1140 tgctttcaga aatccgaagc taggaaacgc gtgaaccagc tgaggggcat cctgaagctg 1200 ctgcagctgc ttaaggtgca gaatgaggat gtccaacgcg cagtgtgcgg tgctctgagg 1260 aacctcgtgt ttgaagataa cgataataag ttggaagtcg cagaacttaa cggggtacct 1320 cgactgctcc aggtgttgaa acagacacgg gacctggaaa cgaaaaaaca aattaccgac 1380 cacactgtga atctcagaag tcggaatggg tggcctgggg cagtagctca tgcctgtaac 1440 ccttctacat tgggtggcca aggcgggagg attaccagat caggggtacg ggatcaacct 1500 gatcagcacg ggctcctgtg gaacttgtcc tctaatgaca aactgaaaaa cctgatgata 1560 accgaggctc tgctgaccct gacagaaaac attatcatcc ccttctccgg atggccagaa 1620 ggagactatc ctaaagctaa cggcttgctg gacttcgata tcttttataa tgtcacaggg 1680 tgccttagaa atatgagtag cgccggtgcc gatggaagga aggcaatgcg ccggtgtgat 1740 ggtcttatcg attccctggt acattacgtg aggggcacca ttgccgacta ccaaccagac 1800 gataaagcaa ccgagaattg cgtgtgcatc ctgcacaatt tgagctacca actcgaagct 1860 gaactgcctg agaaatattc ccaaaatatt tatatccaga atcggaatat ccagaccgat 1920 aataacaaga gcataggatg ctttggttct agaagccgca aggtcaagga acagtaccag 1980 gatgtaccta tgccagagga aaaatcaaac cccaaaggag tggaatggct gtggcattcc 2040 atcgtgatca ggatgtacct gagtctgatt gctaagagcg tgaggaacta tacacaggag 2100 gcttcccttg gcgcactgca aaatctgacc gccggatctg ggccaatgcc aacaagcgtt 2160 gctcaaacag tagtgcaaaa ggaatctggc cttcagcaca ctaggaaaat gcttcatgtg 2220 ggagatcctt ctgtgaagaa gacggctatt agcctgctcc gcaacttgag cagaaacctt 2280 tctttgcaga atgagattgc gaaagagacg ctccctgacc tggtgtccat tataccagac 2340 acggtccctt ccacagatct tctgattgaa acgaccgctt ccgcatgtta caccctgaat 2400 aatattattc aaaactcata ccaaaatgct agagacctgc tgaacactgg ggggatccag 2460 aagattatgg caatttcagc cggcgatgcc tatgctagta ataaagcctc caaggccgcc 2520 agtgtattgc tgtatagtct gtgggcacat acagaactgc accacgcata taagaaggcc 2580 cagtttaaaa aaaccgattt cgtaaactct cggactgcaa aagcctacca ttcactgaaa 2640 gattga 2646 <210> SEQ ID NO 89 <211> LENGTH: 4650 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Made in Lab - polynucleotide sequence of vector genome <400> SEQUENCE: 89 gcgcgctcgc tcgctcactg aggccgcccg ggcaaagccc gggcgtcggg cgacctttgg 60 tcgcccggcc tcagtgagcg agcgagcgcg cagagaggga gtggccaact ccatcactag 120 gggttccttg tagttaatga ttaacccgcc atgctactta tctacgtact ctggagacgc 180 gtacccttca gattaaaaat aactgaggta agggcctggg taggggaggt ggtgtgagac 240 gctcctgtct ctcctctatc tgcccatcgg ccctttgggg aggaggaatg tgcccaagga 300 ctaaaaaaag gccatggagc cagaggggcg agggcaacag acctttcatg ggcaaacctt 360 ggggccctgc tgtctagcat gccccactac gggtctaggc tgcccatgta aggaggcaag 420 gcctggggac acccgagatg cctggttata attaacccag acatgtggct gccccccccc 480 ccccaacacc tgctgcctct aaaaataacc ctgtccctgg tggatcccct gcatgcgaag 540 atcttcgaac aaggctgtgg gggactgagg gcaggctgta acaggcttgg gggccagggc 600 ttatacgtgc ctgggactcc caaagtatta ctgttccatg ttcccggcga agggccagct 660 gtcccccgcc agctagactc agcacttagt ttaggaacca gtgagcaagt cagcccttgg 720 ggcagcccat acaaggccat ggggctgggc aagctgcacg cctgggtccg gggtgggcac 780 ggtgcccggg caacgagctg aaagctcatc tgctctcagg ggcccctccc tggggacagc 840 ccctcctggc tagtcacacc ctgtaggctc ctctatataa cccaggggca caggggctgc 900 cctcattcta ccaccacctc cacagcacag acagacactc aggagccagc cagggtaagt 960 ttagtctttt tgtcttttat ttcaggtccc ggatccggtg gtggtgcaaa tcaaagaact 1020 gctcctcagt ggatgttgcc tttacttcta ggcctgtacg gaagtgttac ttctgctcta 1080 aaagctgcgg aattgtaccc gcgccaccat ggcagccccc ggcgccccag ctgagtacgg 1140 ctacatccgg accgtcctgg gccagcagat cctgggacaa ctggacagct ccagcctggc 1200 gctgccctcc gaggccaagc tgaagctggc ggggagcagc ggccgcggcg gccagacagt 1260 caagagcctg cggatccagg agcaggtgca gcagaccctc gcccggaagg gccgcagctc 1320 cgtgggcaac ggaaatcttc accgaaccag cagtgttcct gagtatgtct acaacctaca 1380 cttggttgaa aatgattttg ttggaggccg ttcccctgtt cctaaaacct atgacatgct 1440 aaaggctggc acaactgcca cttatgaagg tcgctgggga agaggaacag cacagtacag 1500 ctcccagaag tccgtggaag aaaggtcctt gaggcatcct ctgaggagac tggagatttc 1560 tcctgacagc agcccggaga gggctcacta cacgcacagc gattaccagt acagccagag 1620 aagccaggct gggcacaccc tgcaccacca agaaagcagg cgggccgccc tcctagtgcc 1680 accgagatat gctcgttccg agatcgtggg ggtcagccgt gctggcacca caagcaggca 1740 gcgccacttt gacacatacc acagacagta ccagcatggc tctgttagcg acaccgtttt 1800 tgacagcatc cctgccaacc cggccctgct cacgtacccc aggccaggga ccagccgcag 1860 catgggcaac ctcttggaga aggagaacta cctgacggca gggctcactg tcgggcaggt 1920 caggccgctg gtgcccctgc agcccgtcac tcagaacagg gcttccaggt cctcctggca 1980 tcagagctcc ttccacagca cccgcacgct gagggaagct gggcccagtg tcgccgtgga 2040 ttccagcggg aggagagcgc acttgactgt cggccaggcg gccgcagggg gaagtgggaa 2100 tctgctcact gagagaagca ctttcactga ctcccagctg gggaatgcag acatggagat 2160 gactctggag cgagcagtga gtatgctcga ggcagaccac atgctgccat ccaggatttc 2220 tgctgcagct actttcatac agcacgagtg cttccagaaa tctgaagctc ggaagagggt 2280 taaccagctt cgtggcatcc tcaagcttct gcagctccta aaagttcaga atgaagacgt 2340 tcagcgagct gtgtgtgggg ccttgagaaa cttagtattt gaagacaatg acaacaaatt 2400 ggaggtggct gaactaaatg gggtacctcg gctgctccag gtgctgaagc aaaccagaga 2460 cttggagact aaaaaacaaa taacaggttt gctgtggaat ttgtcatcta atgacaaact 2520 caagaatctc atgataacag aagcattgct tacgctgacg gagaatatca tcatcccctt 2580 ttctgggtgg cctgaaggag actacccaaa agcaaatggt ttgctcgatt ttgacatatt 2640 ctacaacgtc actggatgcc taagaaacat gagttctgct ggcgctgatg ggagaaaagc 2700 gatgagaaga tgtgacggac tcattgactc actggtccat tatgtcagag gaaccattgc 2760 agattaccag ccagatgaca aggccacgga gaattgtgtg tgcattcttc ataacctctc 2820 ctaccagctg gaggcagagc tcccagagaa atattcccag aatatctata ttcaaaaccg 2880 gaatatccag actgacaaca acaaaagtat tggatgtttt ggcagtcgaa gcaggaaagt 2940 aaaagagcaa taccaggacg tgccgatgcc ggaggaaaag agcaacccca agggcgtgga 3000 gtggctgtgg cattccattg ttataaggat gtatctgtcc ttgatcgcca aaagtgtccg 3060 caactacaca caagaagcat ccttaggagc tctgcagaac ctcacggccg gaagtggacc 3120 aatgccgaca tcagtggctc agacagttgt ccagaaggaa agtggcctgc agcacacccg 3180 aaagatgctg catgttggtg acccaagtgt gaaaaagaca gccatctcgc tgctgaggaa 3240 tctgtcccgg aatctttctc tgcagaatga aattgccaaa gaaactctcc ctgatttggt 3300 ttccatcatt cctgacacag tcccgagtac tgaccttctc attgaaacta cagcctctgc 3360 ctgttacaca ttgaacaaca taatccaaaa cagttaccag aatgcacgcg accttctaaa 3420 caccgggggc atccagaaaa ttatggccat tagtgcaggc gatgcctatg cctccaacaa 3480 agcaagtaaa gctgcttccg tccttctgta ttctctgtgg gcacacacgg aactgcatca 3540 tgcctacaag aaggctcagt ttaagaagac agattttgtc aacagccgga ctgccaaagc 3600 ctaccactcc cttaaagact gatcaacctc tggattacaa aatttgtgaa agattgactg 3660 gtattcttaa ctatgttgct ccttttacgc tatgtggata cgctgcttta atgcctttgt 3720 atcatgctat tgcttcccgt atggctttca ttttctcctc cttgtataaa tcctggttgc 3780 tgtctcttta tgaggagttg tggcccgttg tcaggcaacg tggcgtggtg tgcactgtgt 3840 ttgctgacgc aacccccact ggttggggca ttgccaccac ctgtcagctc ctttccggga 3900 ctttcgcttt ccccctccct attgccacgg cggaactcat cgccgcctgc cttgcccgct 3960 gctggacagg ggctcggctg ttgggcactg acaattccgt ggtgttgtcg gggaaatcat 4020 cgtcctttcc ttggctgctc gcctgtgttg ccacctggat tctgcgcggg acgtccttct 4080 gctacgtccc ttcggccctc aatccagcgg accttccttc ccgcggcctg ctgccggctc 4140 tgcggcctct tccgcgtctt cgccttcgcc ctcagacgag tcggatctcc ctttgggccg 4200 cctccccgca tcattgcctg cccgggtggc atccctgtga cccctcccca gtgcctctcc 4260 tggccctgga agttgccact ccagtgccca ccagccttgt cctaataaaa ttaagttgca 4320 tcattttgtc tgactaggtg tccttctata atattatggg gtggaggggg gtggtatgga 4380 gcaaggggcc caagttggga agaaacctgt agggcctgcg ttacccaggc tggagtgcag 4440 tggcacattt ctgctcactg caacctcctc ctccctgggt tctacgtaga taagtagcat 4500 ggcgggttaa tcattaacta caaggaaccc ctagtgatgg agttggccac tccctctctg 4560 cgcgctcgct cgctcactga ggccgggcga ccaaaggtcg cccgacgccc gggctttgcc 4620 cgggcggcct cagtgagcga gcgagcgcgc 4650 <210> SEQ ID NO 90 <211> LENGTH: 4274 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Made in Lab - polynucleotide sequence of vector genome <400> SEQUENCE: 90 gcgcgctcgc tcgctcactg aggccgcccg ggcaaagccc gggcgtcggg cgacctttgg 60 tcgcccggcc tcagtgagcg agcgagcgcg cagagaggga gtggccaact ccatcactag 120 gggttccttg tagttaatga ttaacccgcc atgctactta tctacgtact ctggagacgc 180 gtctcagtcc attaggagcc agtagcctgg aagatgtctt tacccccagc atcagttcaa 240 gtggagcagc acataactct tgccctctgc cttccaagat tctggtgctg agacttatgg 300 agtgtcttgg aggttgcctt ctgcccccca accctgctcc cagctggccc tcccaggcct 360 gggttgctgg cctctgcttt atcaggattc tcaagaggga cagctggttt atgttgcatg 420 actgttccct gcatatctgc tctggtttta aatagcttat ctgagcagct ggaggaccac 480 atgggcttat atggcgtggg gtacatgttc ctgtagcctt gtccctggca cctgccaaaa 540 tagcagccaa caccccccac ccccaccgcc atccccctgc cccacccgtc ccctgtcgca 600 cattcctccc tccgcagggc tggctcacca ggccccagcc cacatgcctg cttaaagccc 660 tctccatcct ctgcctcacc cagtccccgc tgagactgag cagacgcctc caggatctgt 720 cggcaggcca ccatggcagc ccccggcgcc ccagctgagt acggctacat ccggaccgtc 780 ctgggccagc agatcctggg acaactggac agctccagcc tggcgctgcc ctccgaggcc 840 aagctgaagc tggcggggag cagcggccgc ggcggccaga cagtcaagag cctgcggatc 900 caggagcagg tgcagcagac cctcgcccgg aagggccgca gctccgtggg caacggaaat 960 cttcaccgaa ccagcagtgt tcctgagtat gtctacaacc tacacttggt tgaaaatgat 1020 tttgttggag gccgttcccc tgttcctaaa acctatgaca tgctaaaggc tggcacaact 1080 gccacttatg aaggtcgctg gggaagagga acagcacagt acagctccca gaagtccgtg 1140 gaagaaaggt ccttgaggca tcctctgagg agactggaga tttctcctga cagcagcccg 1200 gagagggctc actacacgca cagcgattac cagtacagcc agagaagcca ggctgggcac 1260 accctgcacc accaagaaag caggcgggcc gccctcctag tgccaccgag atatgctcgt 1320 tccgagatcg tgggggtcag ccgtgctggc accacaagca ggcagcgcca ctttgacaca 1380 taccacagac agtaccagca tggctctgtt agcgacaccg tttttgacag catccctgcc 1440 aacccggccc tgctcacgta ccccaggcca gggaccagcc gcagcatggg caacctcttg 1500 gagaaggaga actacctgac ggcagggctc actgtcgggc aggtcaggcc gctggtgccc 1560 ctgcagcccg tcactcagaa cagggcttcc aggtcctcct ggcatcagag ctccttccac 1620 agcacccgca cgctgaggga agctgggccc agtgtcgccg tggattccag cgggaggaga 1680 gcgcacttga ctgtcggcca ggcggccgca gggggaagtg ggaatctgct cactgagaga 1740 agcactttca ctgactccca gctggggaat gcagacatgg agatgactct ggagcgagca 1800 gtgagtatgc tcgaggcaga ccacatgctg ccatccagga tttctgctgc agctactttc 1860 atacagcacg agtgcttcca gaaatctgaa gctcggaaga gggttaacca gcttcgtggc 1920 atcctcaagc ttctgcagct cctaaaagtt cagaatgaag acgttcagcg agctgtgtgt 1980 ggggccttga gaaacttagt atttgaagac aatgacaaca aattggaggt ggctgaacta 2040 aatggggtac ctcggctgct ccaggtgctg aagcaaacca gagacttgga gactaaaaaa 2100 caaataacag gtttgctgtg gaatttgtca tctaatgaca aactcaagaa tctcatgata 2160 acagaagcat tgcttacgct gacggagaat atcatcatcc ccttttctgg gtggcctgaa 2220 ggagactacc caaaagcaaa tggtttgctc gattttgaca tattctacaa cgtcactgga 2280 tgcctaagaa acatgagttc tgctggcgct gatgggagaa aagcgatgag aagatgtgac 2340 ggactcattg actcactggt ccattatgtc agaggaacca ttgcagatta ccagccagat 2400 gacaaggcca cggagaattg tgtgtgcatt cttcataacc tctcctacca gctggaggca 2460 gagctcccag agaaatattc ccagaatatc tatattcaaa accggaatat ccagactgac 2520 aacaacaaaa gtattggatg ttttggcagt cgaagcagga aagtaaaaga gcaataccag 2580 gacgtgccga tgccggagga aaagagcaac cccaagggcg tggagtggct gtggcattcc 2640 attgttataa ggatgtatct gtccttgatc gccaaaagtg tccgcaacta cacacaagaa 2700 gcatccttag gagctctgca gaacctcacg gccggaagtg gaccaatgcc gacatcagtg 2760 gctcagacag ttgtccagaa ggaaagtggc ctgcagcaca cccgaaagat gctgcatgtt 2820 ggtgacccaa gtgtgaaaaa gacagccatc tcgctgctga ggaatctgtc ccggaatctt 2880 tctctgcaga atgaaattgc caaagaaact ctccctgatt tggtttccat cattcctgac 2940 acagtcccga gtactgacct tctcattgaa actacagcct ctgcctgtta cacattgaac 3000 aacataatcc aaaacagtta ccagaatgca cgcgaccttc taaacaccgg gggcatccag 3060 aaaattatgg ccattagtgc aggcgatgcc tatgcctcca acaaagcaag taaagctgct 3120 tccgtccttc tgtattctct gtgggcacac acggaactgc atcatgccta caagaaggct 3180 cagtttaaga agacagattt tgtcaacagc cggactgcca aagcctacca ctcccttaaa 3240 gactgatcaa cctctggatt acaaaatttg tgaaagattg actggtattc ttaactatgt 3300 tgctcctttt acgctatgtg gatacgctgc tttaatgcct ttgtatcatg ctattgcttc 3360 ccgtatggct ttcattttct cctccttgta taaatcctgg ttgctgtctc tttatgagga 3420 gttgtggccc gttgtcaggc aacgtggcgt ggtgtgcact gtgtttgctg acgcaacccc 3480 cactggttgg ggcattgcca ccacctgtca gctcctttcc gggactttcg ctttccccct 3540 ccctattgcc acggcggaac tcatcgccgc ctgccttgcc cgctgctgga caggggctcg 3600 gctgttgggc actgacaatt ccgtggtgtt gtcggggaaa tcatcgtcct ttccttggct 3660 gctcgcctgt gttgccacct ggattctgcg cgggacgtcc ttctgctacg tcccttcggc 3720 cctcaatcca gcggaccttc cttcccgcgg cctgctgccg gctctgcggc ctcttccgcg 3780 tcttcgcctt cgccctcaga cgagtcggat ctccctttgg gccgcctccc cgcatcattg 3840 cctgcccggg tggcatccct gtgacccctc cccagtgcct ctcctggccc tggaagttgc 3900 cactccagtg cccaccagcc ttgtcctaat aaaattaagt tgcatcattt tgtctgacta 3960 ggtgtccttc tataatatta tggggtggag gggggtggta tggagcaagg ggcccaagtt 4020 gggaagaaac ctgtagggcc tgcgttaccc aggctggagt gcagtggcac atttctgctc 4080 actgcaacct cctcctccct gggttctacg tagataagta gcatggcggg ttaatcatta 4140 actacaagga acccctagtg atggagttgg ccactccctc tctgcgcgct cgctcgctca 4200 ctgaggccgg gcgaccaaag gtcgcccgac gcccgggctt tgcccgggcg gcctcagtga 4260 gcgagcgagc gcgc 4274 <210> SEQ ID NO 91 <211> LENGTH: 4782 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Made in Lab - polynucleotide sequence of vector genome <400> SEQUENCE: 91 gcgcgctcgc tcgctcactg aggccgcccg ggcaaagccc gggcgtcggg cgacctttgg 60 tcgcccggcc tcagtgagcg agcgagcgcg cagagaggga gtggccaact ccatcactag 120 gggttccttg tagttaatga ttaacccgcc atgctactta tctacgtact ctggagacgc 180 gtacccttca gattaaaaat aactgaggta agggcctggg taggggaggt ggtgtgagac 240 gctcctgtct ctcctctatc tgcccatcgg ccctttgggg aggaggaatg tgcccaagga 300 ctaaaaaaag gccatggagc cagaggggcg agggcaacag acctttcatg ggcaaacctt 360 ggggccctgc tgtctagcat gccccactac gggtctaggc tgcccatgta aggaggcaag 420 gcctggggac acccgagatg cctggttata attaacccag acatgtggct gccccccccc 480 ccccaacacc tgctgcctct aaaaataacc ctgtccctgg tggatcccct gcatgcgaag 540 atcttcgaac aaggctgtgg gggactgagg gcaggctgta acaggcttgg gggccagggc 600 ttatacgtgc ctgggactcc caaagtatta ctgttccatg ttcccggcga agggccagct 660 gtcccccgcc agctagactc agcacttagt ttaggaacca gtgagcaagt cagcccttgg 720 ggcagcccat acaaggccat ggggctgggc aagctgcacg cctgggtccg gggtgggcac 780 ggtgcccggg caacgagctg aaagctcatc tgctctcagg ggcccctccc tggggacagc 840 ccctcctggc tagtcacacc ctgtaggctc ctctatataa cccaggggca caggggctgc 900 cctcattcta ccaccacctc cacagcacag acagacactc aggagccagc cagggtaagt 960 ttagtctttt tgtcttttat ttcaggtccc ggatccggtg gtggtgcaaa tcaaagaact 1020 gctcctcagt ggatgttgcc tttacttcta ggcctgtacg gaagtgttac ttctgctcta 1080 aaagctgcgg aattgtaccc gcgccaccat ggcagccccc ggcgccccag ctgagtacgg 1140 ctacatccgg accgtcctgg gccagcagat cctgggacaa ctggacagct ccagcctggc 1200 gctgccctcc gaggccaagc tgaagctggc ggggagcagc ggccgcggcg gccagacagt 1260 caagagcctg cggatccagg agcaggtgca gcagaccctc gcccggaagg gccgcagctc 1320 cgtgggcaac ggaaatcttc accgaaccag cagtgttcct gagtatgtct acaacctaca 1380 cttggttgaa aatgattttg ttggaggccg ttcccctgtt cctaaaacct atgacatgct 1440 aaaggctggc acaactgcca cttatgaagg tcgctgggga agaggaacag cacagtacag 1500 ctcccagaag tccgtggaag aaaggtcctt gaggcatcct ctgaggagac tggagatttc 1560 tcctgacagc agcccggaga gggctcacta cacgcacagc gattaccagt acagccagag 1620 aagccaggct gggcacaccc tgcaccacca agaaagcagg cgggccgccc tcctagtgcc 1680 accgagatat gctcgttccg agatcgtggg ggtcagccgt gctggcacca caagcaggca 1740 gcgccacttt gacacatacc acagacagta ccagcatggc tctgttagcg acaccgtttt 1800 tgacagcatc cctgccaacc cggccctgct cacgtacccc aggccaggga ccagccgcag 1860 catgggcaac ctcttggaga aggagaacta cctgacggca gggctcactg tcgggcaggt 1920 caggccgctg gtgcccctgc agcccgtcac tcagaacagg gcttccaggt cctcctggca 1980 tcagagctcc ttccacagca cccgcacgct gagggaagct gggcccagtg tcgccgtgga 2040 ttccagcggg aggagagcgc acttgactgt cggccaggcg gccgcagggg gaagtgggaa 2100 tctgctcact gagagaagca ctttcactga ctcccagctg gggaatgcag acatggagat 2160 gactctggag cgagcagtga gtatgctcga ggcagaccac atgctgccat ccaggatttc 2220 tgctgcagct actttcatac agcacgagtg cttccagaaa tctgaagctc ggaagagggt 2280 taaccagctt cgtggcatcc tcaagcttct gcagctccta aaagttcaga atgaagacgt 2340 tcagcgagct gtgtgtgggg ccttgagaaa cttagtattt gaagacaatg acaacaaatt 2400 ggaggtggct gaactaaatg gggtacctcg gctgctccag gtgctgaagc aaaccagaga 2460 cttggagact aaaaaacaaa taacagacca tacagtcaat ttaagaagta ggaatggctg 2520 gccgggcgcg gtggctcacg cctgtaatcc cagcactttg ggaggccaag gcgggcggat 2580 cacgaggtca ggagttcgag accagcctga ccaacatggt ttgctgtgga atttgtcatc 2640 taatgacaaa ctcaagaatc tcatgataac agaagcattg cttacgctga cggagaatat 2700 catcatcccc ttttctgggt ggcctgaagg agactaccca aaagcaaatg gtttgctcga 2760 ttttgacata ttctacaacg tcactggatg cctaagaaac atgagttctg ctggcgctga 2820 tgggagaaaa gcgatgagaa gatgtgacgg actcattgac tcactggtcc attatgtcag 2880 aggaaccatt gcagattacc agccagatga caaggccacg gagaattgtg tgtgcattct 2940 tcataacctc tcctaccagc tggaggcaga gctcccagag aaatattccc agaatatcta 3000 tattcaaaac cggaatatcc agactgacaa caacaaaagt attggatgtt ttggcagtcg 3060 aagcaggaaa gtaaaagagc aataccagga cgtgccgatg ccggaggaaa agagcaaccc 3120 caagggcgtg gagtggctgt ggcattccat tgttataagg atgtatctgt ccttgatcgc 3180 caaaagtgtc cgcaactaca cacaagaagc atccttagga gctctgcaga acctcacggc 3240 cggaagtgga ccaatgccga catcagtggc tcagacagtt gtccagaagg aaagtggcct 3300 gcagcacacc cgaaagatgc tgcatgttgg tgacccaagt gtgaaaaaga cagccatctc 3360 gctgctgagg aatctgtccc ggaatctttc tctgcagaat gaaattgcca aagaaactct 3420 ccctgatttg gtttccatca ttcctgacac agtcccgagt actgaccttc tcattgaaac 3480 tacagcctct gcctgttaca cattgaacaa cataatccaa aacagttacc agaatgcacg 3540 cgaccttcta aacaccgggg gcatccagaa aattatggcc attagtgcag gcgatgccta 3600 tgcctccaac aaagcaagta aagctgcttc cgtccttctg tattctctgt gggcacacac 3660 ggaactgcat catgcctaca agaaggctca gtttaagaag acagattttg tcaacagccg 3720 gactgccaaa gcctaccact cccttaaaga ctgatcaacc tctggattac aaaatttgtg 3780 aaagattgac tggtattctt aactatgttg ctccttttac gctatgtgga tacgctgctt 3840 taatgccttt gtatcatgct attgcttccc gtatggcttt cattttctcc tccttgtata 3900 aatcctggtt gctgtctctt tatgaggagt tgtggcccgt tgtcaggcaa cgtggcgtgg 3960 tgtgcactgt gtttgctgac gcaaccccca ctggttgggg cattgccacc acctgtcagc 4020 tcctttccgg gactttcgct ttccccctcc ctattgccac ggcggaactc atcgccgcct 4080 gccttgcccg ctgctggaca ggggctcggc tgttgggcac tgacaattcc gtggtgttgt 4140 cggggaaatc atcgtccttt ccttggctgc tcgcctgtgt tgccacctgg attctgcgcg 4200 ggacgtcctt ctgctacgtc ccttcggccc tcaatccagc ggaccttcct tcccgcggcc 4260 tgctgccggc tctgcggcct cttccgcgtc ttcgccttcg ccctcagacg agtcggatct 4320 ccctttgggc cgcctccccg catcattgcc tgcccgggtg gcatccctgt gacccctccc 4380 cagtgcctct cctggccctg gaagttgcca ctccagtgcc caccagcctt gtcctaataa 4440 aattaagttg catcattttg tctgactagg tgtccttcta taatattatg gggtggaggg 4500 gggtggtatg gagcaagggg cccaagttgg gaagaaacct gtagggcctg cgttacccag 4560 gctggagtgc agtggcacat ttctgctcac tgcaacctcc tcctccctgg gttctacgta 4620 gataagtagc atggcgggtt aatcattaac tacaaggaac ccctagtgat ggagttggcc 4680 actccctctc tgcgcgctcg ctcgctcact gaggccgggc gaccaaaggt cgcccgacgc 4740 ccgggctttg cccgggcggc ctcagtgagc gagcgagcgc gc 4782 <210> SEQ ID NO 92 <211> LENGTH: 4406 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Made in Lab - polynucleotide sequence of vector genome <400> SEQUENCE: 92 gcgcgctcgc tcgctcactg aggccgcccg ggcaaagccc gggcgtcggg cgacctttgg 60 tcgcccggcc tcagtgagcg agcgagcgcg cagagaggga gtggccaact ccatcactag 120 gggttccttg tagttaatga ttaacccgcc atgctactta tctacgtact ctggagacgc 180 gtctcagtcc attaggagcc agtagcctgg aagatgtctt tacccccagc atcagttcaa 240 gtggagcagc acataactct tgccctctgc cttccaagat tctggtgctg agacttatgg 300 agtgtcttgg aggttgcctt ctgcccccca accctgctcc cagctggccc tcccaggcct 360 gggttgctgg cctctgcttt atcaggattc tcaagaggga cagctggttt atgttgcatg 420 actgttccct gcatatctgc tctggtttta aatagcttat ctgagcagct ggaggaccac 480 atgggcttat atggcgtggg gtacatgttc ctgtagcctt gtccctggca cctgccaaaa 540 tagcagccaa caccccccac ccccaccgcc atccccctgc cccacccgtc ccctgtcgca 600 cattcctccc tccgcagggc tggctcacca ggccccagcc cacatgcctg cttaaagccc 660 tctccatcct ctgcctcacc cagtccccgc tgagactgag cagacgcctc caggatctgt 720 cggcaggcca ccatggcagc ccccggcgcc ccagctgagt acggctacat ccggaccgtc 780 ctgggccagc agatcctggg acaactggac agctccagcc tggcgctgcc ctccgaggcc 840 aagctgaagc tggcggggag cagcggccgc ggcggccaga cagtcaagag cctgcggatc 900 caggagcagg tgcagcagac cctcgcccgg aagggccgca gctccgtggg caacggaaat 960 cttcaccgaa ccagcagtgt tcctgagtat gtctacaacc tacacttggt tgaaaatgat 1020 tttgttggag gccgttcccc tgttcctaaa acctatgaca tgctaaaggc tggcacaact 1080 gccacttatg aaggtcgctg gggaagagga acagcacagt acagctccca gaagtccgtg 1140 gaagaaaggt ccttgaggca tcctctgagg agactggaga tttctcctga cagcagcccg 1200 gagagggctc actacacgca cagcgattac cagtacagcc agagaagcca ggctgggcac 1260 accctgcacc accaagaaag caggcgggcc gccctcctag tgccaccgag atatgctcgt 1320 tccgagatcg tgggggtcag ccgtgctggc accacaagca ggcagcgcca ctttgacaca 1380 taccacagac agtaccagca tggctctgtt agcgacaccg tttttgacag catccctgcc 1440 aacccggccc tgctcacgta ccccaggcca gggaccagcc gcagcatggg caacctcttg 1500 gagaaggaga actacctgac ggcagggctc actgtcgggc aggtcaggcc gctggtgccc 1560 ctgcagcccg tcactcagaa cagggcttcc aggtcctcct ggcatcagag ctccttccac 1620 agcacccgca cgctgaggga agctgggccc agtgtcgccg tggattccag cgggaggaga 1680 gcgcacttga ctgtcggcca ggcggccgca gggggaagtg ggaatctgct cactgagaga 1740 agcactttca ctgactccca gctggggaat gcagacatgg agatgactct ggagcgagca 1800 gtgagtatgc tcgaggcaga ccacatgctg ccatccagga tttctgctgc agctactttc 1860 atacagcacg agtgcttcca gaaatctgaa gctcggaaga gggttaacca gcttcgtggc 1920 atcctcaagc ttctgcagct cctaaaagtt cagaatgaag acgttcagcg agctgtgtgt 1980 ggggccttga gaaacttagt atttgaagac aatgacaaca aattggaggt ggctgaacta 2040 aatggggtac ctcggctgct ccaggtgctg aagcaaacca gagacttgga gactaaaaaa 2100 caaataacag accatacagt caatttaaga agtaggaatg gctggccggg cgcggtggct 2160 cacgcctgta atcccagcac tttgggaggc caaggcgggc ggatcacgag gtcaggagtt 2220 cgagaccagc ctgaccaaca tggtttgctg tggaatttgt catctaatga caaactcaag 2280 aatctcatga taacagaagc attgcttacg ctgacggaga atatcatcat ccccttttct 2340 gggtggcctg aaggagacta cccaaaagca aatggtttgc tcgattttga catattctac 2400 aacgtcactg gatgcctaag aaacatgagt tctgctggcg ctgatgggag aaaagcgatg 2460 agaagatgtg acggactcat tgactcactg gtccattatg tcagaggaac cattgcagat 2520 taccagccag atgacaaggc cacggagaat tgtgtgtgca ttcttcataa cctctcctac 2580 cagctggagg cagagctccc agagaaatat tcccagaata tctatattca aaaccggaat 2640 atccagactg acaacaacaa aagtattgga tgttttggca gtcgaagcag gaaagtaaaa 2700 gagcaatacc aggacgtgcc gatgccggag gaaaagagca accccaaggg cgtggagtgg 2760 ctgtggcatt ccattgttat aaggatgtat ctgtccttga tcgccaaaag tgtccgcaac 2820 tacacacaag aagcatcctt aggagctctg cagaacctca cggccggaag tggaccaatg 2880 ccgacatcag tggctcagac agttgtccag aaggaaagtg gcctgcagca cacccgaaag 2940 atgctgcatg ttggtgaccc aagtgtgaaa aagacagcca tctcgctgct gaggaatctg 3000 tcccggaatc tttctctgca gaatgaaatt gccaaagaaa ctctccctga tttggtttcc 3060 atcattcctg acacagtccc gagtactgac cttctcattg aaactacagc ctctgcctgt 3120 tacacattga acaacataat ccaaaacagt taccagaatg cacgcgacct tctaaacacc 3180 gggggcatcc agaaaattat ggccattagt gcaggcgatg cctatgcctc caacaaagca 3240 agtaaagctg cttccgtcct tctgtattct ctgtgggcac acacggaact gcatcatgcc 3300 tacaagaagg ctcagtttaa gaagacagat tttgtcaaca gccggactgc caaagcctac 3360 cactccctta aagactgatc aacctctgga ttacaaaatt tgtgaaagat tgactggtat 3420 tcttaactat gttgctcctt ttacgctatg tggatacgct gctttaatgc ctttgtatca 3480 tgctattgct tcccgtatgg ctttcatttt ctcctccttg tataaatcct ggttgctgtc 3540 tctttatgag gagttgtggc ccgttgtcag gcaacgtggc gtggtgtgca ctgtgtttgc 3600 tgacgcaacc cccactggtt ggggcattgc caccacctgt cagctccttt ccgggacttt 3660 cgctttcccc ctccctattg ccacggcgga actcatcgcc gcctgccttg cccgctgctg 3720 gacaggggct cggctgttgg gcactgacaa ttccgtggtg ttgtcgggga aatcatcgtc 3780 ctttccttgg ctgctcgcct gtgttgccac ctggattctg cgcgggacgt ccttctgcta 3840 cgtcccttcg gccctcaatc cagcggacct tccttcccgc ggcctgctgc cggctctgcg 3900 gcctcttccg cgtcttcgcc ttcgccctca gacgagtcgg atctcccttt gggccgcctc 3960 cccgcatcat tgcctgcccg ggtggcatcc ctgtgacccc tccccagtgc ctctcctggc 4020 cctggaagtt gccactccag tgcccaccag ccttgtccta ataaaattaa gttgcatcat 4080 tttgtctgac taggtgtcct tctataatat tatggggtgg aggggggtgg tatggagcaa 4140 ggggcccaag ttgggaagaa acctgtaggg cctgcgttac ccaggctgga gtgcagtggc 4200 acatttctgc tcactgcaac ctcctcctcc ctgggttcta cgtagataag tagcatggcg 4260 ggttaatcat taactacaag gaacccctag tgatggagtt ggccactccc tctctgcgcg 4320 ctcgctcgct cactgaggcc gggcgaccaa aggtcgcccg acgcccgggc tttgcccggg 4380 cggcctcagt gagcgagcga gcgcgc 4406 <210> SEQ ID NO 93 <211> LENGTH: 4237 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Made in Lab - expression cassette polynucleotide <400> SEQUENCE: 93 acccttcaga ttaaaaataa ctgaggtaag ggcctgggta ggggaggtgg tgtgagacgc 60 tcctgtctct cctctatctg cccatcggcc ctttggggag gaggaatgtg cccaaggact 120 aaaaaaaggc catggagcca gaggggcgag ggcaacagac ctttcatggg caaaccttgg 180 ggccctgctg tctagcatgc cccactacgg gtctaggctg cccatgtaag gaggcaaggc 240 ctggggacac ccgagatgcc tggttataat taacccagac atgtggctgc cccccccccc 300 ccaacacctg ctgcctctaa aaataaccct gtccctggtg gatcccctgc atgcgaagat 360 cttcgaacaa ggctgtgggg gactgagggc aggctgtaac aggcttgggg gccagggctt 420 atacgtgcct gggactccca aagtattact gttccatgtt cccggcgaag ggccagctgt 480 cccccgccag ctagactcag cacttagttt aggaaccagt gagcaagtca gcccttgggg 540 cagcccatac aaggccatgg ggctgggcaa gctgcacgcc tgggtccggg gtgggcacgg 600 tgcccgggca acgagctgaa agctcatctg ctctcagggg cccctccctg gggacagccc 660 ctcctggcta gtcacaccct gtaggctcct ctatataacc caggggcaca ggggctgccc 720 tcattctacc accacctcca cagcacagac agacactcag gagccagcca gggtaagttt 780 agtctttttg tcttttattt caggtcccgg atccggtggt ggtgcaaatc aaagaactgc 840 tcctcagtgg atgttgcctt tacttctagg cctgtacgga agtgttactt ctgctctaaa 900 agctgcggaa ttgtacccgc gccaccatgg cagcccccgg cgccccagct gagtacggct 960 acatccggac cgtcctgggc cagcagatcc tgggacaact ggacagctcc agcctggcgc 1020 tgccctccga ggccaagctg aagctggcgg ggagcagcgg ccgcggcggc cagacagtca 1080 agagcctgcg gatccaggag caggtgcagc agaccctcgc ccggaagggc cgcagctccg 1140 tgggcaacgg aaatcttcac cgaaccagca gtgttcctga gtatgtctac aacctacact 1200 tggttgaaaa tgattttgtt ggaggccgtt cccctgttcc taaaacctat gacatgctaa 1260 aggctggcac aactgccact tatgaaggtc gctggggaag aggaacagca cagtacagct 1320 cccagaagtc cgtggaagaa aggtccttga ggcatcctct gaggagactg gagatttctc 1380 ctgacagcag cccggagagg gctcactaca cgcacagcga ttaccagtac agccagagaa 1440 gccaggctgg gcacaccctg caccaccaag aaagcaggcg ggccgccctc ctagtgccac 1500 cgagatatgc tcgttccgag atcgtggggg tcagccgtgc tggcaccaca agcaggcagc 1560 gccactttga cacataccac agacagtacc agcatggctc tgttagcgac accgtttttg 1620 acagcatccc tgccaacccg gccctgctca cgtaccccag gccagggacc agccgcagca 1680 tgggcaacct cttggagaag gagaactacc tgacggcagg gctcactgtc gggcaggtca 1740 ggccgctggt gcccctgcag cccgtcactc agaacagggc ttccaggtcc tcctggcatc 1800 agagctcctt ccacagcacc cgcacgctga gggaagctgg gcccagtgtc gccgtggatt 1860 ccagcgggag gagagcgcac ttgactgtcg gccaggcggc cgcaggggga agtgggaatc 1920 tgctcactga gagaagcact ttcactgact cccagctggg gaatgcagac atggagatga 1980 ctctggagcg agcagtgagt atgctcgagg cagaccacat gctgccatcc aggatttctg 2040 ctgcagctac tttcatacag cacgagtgct tccagaaatc tgaagctcgg aagagggtta 2100 accagcttcg tggcatcctc aagcttctgc agctcctaaa agttcagaat gaagacgttc 2160 agcgagctgt gtgtggggcc ttgagaaact tagtatttga agacaatgac aacaaattgg 2220 aggtggctga actaaatggg gtacctcggc tgctccaggt gctgaagcaa accagagact 2280 tggagactaa aaaacaaata acaggtttgc tgtggaattt gtcatctaat gacaaactca 2340 agaatctcat gataacagaa gcattgctta cgctgacgga gaatatcatc atcccctttt 2400 ctgggtggcc tgaaggagac tacccaaaag caaatggttt gctcgatttt gacatattct 2460 acaacgtcac tggatgccta agaaacatga gttctgctgg cgctgatggg agaaaagcga 2520 tgagaagatg tgacggactc attgactcac tggtccatta tgtcagagga accattgcag 2580 attaccagcc agatgacaag gccacggaga attgtgtgtg cattcttcat aacctctcct 2640 accagctgga ggcagagctc ccagagaaat attcccagaa tatctatatt caaaaccgga 2700 atatccagac tgacaacaac aaaagtattg gatgttttgg cagtcgaagc aggaaagtaa 2760 aagagcaata ccaggacgtg ccgatgccgg aggaaaagag caaccccaag ggcgtggagt 2820 ggctgtggca ttccattgtt ataaggatgt atctgtcctt gatcgccaaa agtgtccgca 2880 actacacaca agaagcatcc ttaggagctc tgcagaacct cacggccgga agtggaccaa 2940 tgccgacatc agtggctcag acagttgtcc agaaggaaag tggcctgcag cacacccgaa 3000 agatgctgca tgttggtgac ccaagtgtga aaaagacagc catctcgctg ctgaggaatc 3060 tgtcccggaa tctttctctg cagaatgaaa ttgccaaaga aactctccct gatttggttt 3120 ccatcattcc tgacacagtc ccgagtactg accttctcat tgaaactaca gcctctgcct 3180 gttacacatt gaacaacata atccaaaaca gttaccagaa tgcacgcgac cttctaaaca 3240 ccgggggcat ccagaaaatt atggccatta gtgcaggcga tgcctatgcc tccaacaaag 3300 caagtaaagc tgcttccgtc cttctgtatt ctctgtgggc acacacggaa ctgcatcatg 3360 cctacaagaa ggctcagttt aagaagacag attttgtcaa cagccggact gccaaagcct 3420 accactccct taaagactga tcaacctctg gattacaaaa tttgtgaaag attgactggt 3480 attcttaact atgttgctcc ttttacgcta tgtggatacg ctgctttaat gcctttgtat 3540 catgctattg cttcccgtat ggctttcatt ttctcctcct tgtataaatc ctggttgctg 3600 tctctttatg aggagttgtg gcccgttgtc aggcaacgtg gcgtggtgtg cactgtgttt 3660 gctgacgcaa cccccactgg ttggggcatt gccaccacct gtcagctcct ttccgggact 3720 ttcgctttcc ccctccctat tgccacggcg gaactcatcg ccgcctgcct tgcccgctgc 3780 tggacagggg ctcggctgtt gggcactgac aattccgtgg tgttgtcggg gaaatcatcg 3840 tcctttcctt ggctgctcgc ctgtgttgcc acctggattc tgcgcgggac gtccttctgc 3900 tacgtccctt cggccctcaa tccagcggac cttccttccc gcggcctgct gccggctctg 3960 cggcctcttc cgcgtcttcg ccttcgccct cagacgagtc ggatctccct ttgggccgcc 4020 tccccgcatc attgcctgcc cgggtggcat ccctgtgacc cctccccagt gcctctcctg 4080 gccctggaag ttgccactcc agtgcccacc agccttgtcc taataaaatt aagttgcatc 4140 attttgtctg actaggtgtc cttctataat attatggggt ggaggggggt ggtatggagc 4200 aaggggccca agttgggaag aaacctgtag ggcctgc 4237 <210> SEQ ID NO 94 <211> LENGTH: 3861 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Made in Lab - expression cassette polynucleotide <400> SEQUENCE: 94 ctcagtccat taggagccag tagcctggaa gatgtcttta cccccagcat cagttcaagt 60 ggagcagcac ataactcttg ccctctgcct tccaagattc tggtgctgag acttatggag 120 tgtcttggag gttgccttct gccccccaac cctgctccca gctggccctc ccaggcctgg 180 gttgctggcc tctgctttat caggattctc aagagggaca gctggtttat gttgcatgac 240 tgttccctgc atatctgctc tggttttaaa tagcttatct gagcagctgg aggaccacat 300 gggcttatat ggcgtggggt acatgttcct gtagccttgt ccctggcacc tgccaaaata 360 gcagccaaca ccccccaccc ccaccgccat ccccctgccc cacccgtccc ctgtcgcaca 420 ttcctccctc cgcagggctg gctcaccagg ccccagccca catgcctgct taaagccctc 480 tccatcctct gcctcaccca gtccccgctg agactgagca gacgcctcca ggatctgtcg 540 gcaggccacc atggcagccc ccggcgcccc agctgagtac ggctacatcc ggaccgtcct 600 gggccagcag atcctgggac aactggacag ctccagcctg gcgctgccct ccgaggccaa 660 gctgaagctg gcggggagca gcggccgcgg cggccagaca gtcaagagcc tgcggatcca 720 ggagcaggtg cagcagaccc tcgcccggaa gggccgcagc tccgtgggca acggaaatct 780 tcaccgaacc agcagtgttc ctgagtatgt ctacaaccta cacttggttg aaaatgattt 840 tgttggaggc cgttcccctg ttcctaaaac ctatgacatg ctaaaggctg gcacaactgc 900 cacttatgaa ggtcgctggg gaagaggaac agcacagtac agctcccaga agtccgtgga 960 agaaaggtcc ttgaggcatc ctctgaggag actggagatt tctcctgaca gcagcccgga 1020 gagggctcac tacacgcaca gcgattacca gtacagccag agaagccagg ctgggcacac 1080 cctgcaccac caagaaagca ggcgggccgc cctcctagtg ccaccgagat atgctcgttc 1140 cgagatcgtg ggggtcagcc gtgctggcac cacaagcagg cagcgccact ttgacacata 1200 ccacagacag taccagcatg gctctgttag cgacaccgtt tttgacagca tccctgccaa 1260 cccggccctg ctcacgtacc ccaggccagg gaccagccgc agcatgggca acctcttgga 1320 gaaggagaac tacctgacgg cagggctcac tgtcgggcag gtcaggccgc tggtgcccct 1380 gcagcccgtc actcagaaca gggcttccag gtcctcctgg catcagagct ccttccacag 1440 cacccgcacg ctgagggaag ctgggcccag tgtcgccgtg gattccagcg ggaggagagc 1500 gcacttgact gtcggccagg cggccgcagg gggaagtggg aatctgctca ctgagagaag 1560 cactttcact gactcccagc tggggaatgc agacatggag atgactctgg agcgagcagt 1620 gagtatgctc gaggcagacc acatgctgcc atccaggatt tctgctgcag ctactttcat 1680 acagcacgag tgcttccaga aatctgaagc tcggaagagg gttaaccagc ttcgtggcat 1740 cctcaagctt ctgcagctcc taaaagttca gaatgaagac gttcagcgag ctgtgtgtgg 1800 ggccttgaga aacttagtat ttgaagacaa tgacaacaaa ttggaggtgg ctgaactaaa 1860 tggggtacct cggctgctcc aggtgctgaa gcaaaccaga gacttggaga ctaaaaaaca 1920 aataacaggt ttgctgtgga atttgtcatc taatgacaaa ctcaagaatc tcatgataac 1980 agaagcattg cttacgctga cggagaatat catcatcccc ttttctgggt ggcctgaagg 2040 agactaccca aaagcaaatg gtttgctcga ttttgacata ttctacaacg tcactggatg 2100 cctaagaaac atgagttctg ctggcgctga tgggagaaaa gcgatgagaa gatgtgacgg 2160 actcattgac tcactggtcc attatgtcag aggaaccatt gcagattacc agccagatga 2220 caaggccacg gagaattgtg tgtgcattct tcataacctc tcctaccagc tggaggcaga 2280 gctcccagag aaatattccc agaatatcta tattcaaaac cggaatatcc agactgacaa 2340 caacaaaagt attggatgtt ttggcagtcg aagcaggaaa gtaaaagagc aataccagga 2400 cgtgccgatg ccggaggaaa agagcaaccc caagggcgtg gagtggctgt ggcattccat 2460 tgttataagg atgtatctgt ccttgatcgc caaaagtgtc cgcaactaca cacaagaagc 2520 atccttagga gctctgcaga acctcacggc cggaagtgga ccaatgccga catcagtggc 2580 tcagacagtt gtccagaagg aaagtggcct gcagcacacc cgaaagatgc tgcatgttgg 2640 tgacccaagt gtgaaaaaga cagccatctc gctgctgagg aatctgtccc ggaatctttc 2700 tctgcagaat gaaattgcca aagaaactct ccctgatttg gtttccatca ttcctgacac 2760 agtcccgagt actgaccttc tcattgaaac tacagcctct gcctgttaca cattgaacaa 2820 cataatccaa aacagttacc agaatgcacg cgaccttcta aacaccgggg gcatccagaa 2880 aattatggcc attagtgcag gcgatgccta tgcctccaac aaagcaagta aagctgcttc 2940 cgtccttctg tattctctgt gggcacacac ggaactgcat catgcctaca agaaggctca 3000 gtttaagaag acagattttg tcaacagccg gactgccaaa gcctaccact cccttaaaga 3060 ctgatcaacc tctggattac aaaatttgtg aaagattgac tggtattctt aactatgttg 3120 ctccttttac gctatgtgga tacgctgctt taatgccttt gtatcatgct attgcttccc 3180 gtatggcttt cattttctcc tccttgtata aatcctggtt gctgtctctt tatgaggagt 3240 tgtggcccgt tgtcaggcaa cgtggcgtgg tgtgcactgt gtttgctgac gcaaccccca 3300 ctggttgggg cattgccacc acctgtcagc tcctttccgg gactttcgct ttccccctcc 3360 ctattgccac ggcggaactc atcgccgcct gccttgcccg ctgctggaca ggggctcggc 3420 tgttgggcac tgacaattcc gtggtgttgt cggggaaatc atcgtccttt ccttggctgc 3480 tcgcctgtgt tgccacctgg attctgcgcg ggacgtcctt ctgctacgtc ccttcggccc 3540 tcaatccagc ggaccttcct tcccgcggcc tgctgccggc tctgcggcct cttccgcgtc 3600 ttcgccttcg ccctcagacg agtcggatct ccctttgggc cgcctccccg catcattgcc 3660 tgcccgggtg gcatccctgt gacccctccc cagtgcctct cctggccctg gaagttgcca 3720 ctccagtgcc caccagcctt gtcctaataa aattaagttg catcattttg tctgactagg 3780 tgtccttcta taatattatg gggtggaggg gggtggtatg gagcaagggg cccaagttgg 3840 gaagaaacct gtagggcctg c 3861 <210> SEQ ID NO 95 <211> LENGTH: 4369 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Made in Lab - expression cassette polynucleotide <400> SEQUENCE: 95 acccttcaga ttaaaaataa ctgaggtaag ggcctgggta ggggaggtgg tgtgagacgc 60 tcctgtctct cctctatctg cccatcggcc ctttggggag gaggaatgtg cccaaggact 120 aaaaaaaggc catggagcca gaggggcgag ggcaacagac ctttcatggg caaaccttgg 180 ggccctgctg tctagcatgc cccactacgg gtctaggctg cccatgtaag gaggcaaggc 240 ctggggacac ccgagatgcc tggttataat taacccagac atgtggctgc cccccccccc 300 ccaacacctg ctgcctctaa aaataaccct gtccctggtg gatcccctgc atgcgaagat 360 cttcgaacaa ggctgtgggg gactgagggc aggctgtaac aggcttgggg gccagggctt 420 atacgtgcct gggactccca aagtattact gttccatgtt cccggcgaag ggccagctgt 480 cccccgccag ctagactcag cacttagttt aggaaccagt gagcaagtca gcccttgggg 540 cagcccatac aaggccatgg ggctgggcaa gctgcacgcc tgggtccggg gtgggcacgg 600 tgcccgggca acgagctgaa agctcatctg ctctcagggg cccctccctg gggacagccc 660 ctcctggcta gtcacaccct gtaggctcct ctatataacc caggggcaca ggggctgccc 720 tcattctacc accacctcca cagcacagac agacactcag gagccagcca gggtaagttt 780 agtctttttg tcttttattt caggtcccgg atccggtggt ggtgcaaatc aaagaactgc 840 tcctcagtgg atgttgcctt tacttctagg cctgtacgga agtgttactt ctgctctaaa 900 agctgcggaa ttgtacccgc gccaccatgg cagcccccgg cgccccagct gagtacggct 960 acatccggac cgtcctgggc cagcagatcc tgggacaact ggacagctcc agcctggcgc 1020 tgccctccga ggccaagctg aagctggcgg ggagcagcgg ccgcggcggc cagacagtca 1080 agagcctgcg gatccaggag caggtgcagc agaccctcgc ccggaagggc cgcagctccg 1140 tgggcaacgg aaatcttcac cgaaccagca gtgttcctga gtatgtctac aacctacact 1200 tggttgaaaa tgattttgtt ggaggccgtt cccctgttcc taaaacctat gacatgctaa 1260 aggctggcac aactgccact tatgaaggtc gctggggaag aggaacagca cagtacagct 1320 cccagaagtc cgtggaagaa aggtccttga ggcatcctct gaggagactg gagatttctc 1380 ctgacagcag cccggagagg gctcactaca cgcacagcga ttaccagtac agccagagaa 1440 gccaggctgg gcacaccctg caccaccaag aaagcaggcg ggccgccctc ctagtgccac 1500 cgagatatgc tcgttccgag atcgtggggg tcagccgtgc tggcaccaca agcaggcagc 1560 gccactttga cacataccac agacagtacc agcatggctc tgttagcgac accgtttttg 1620 acagcatccc tgccaacccg gccctgctca cgtaccccag gccagggacc agccgcagca 1680 tgggcaacct cttggagaag gagaactacc tgacggcagg gctcactgtc gggcaggtca 1740 ggccgctggt gcccctgcag cccgtcactc agaacagggc ttccaggtcc tcctggcatc 1800 agagctcctt ccacagcacc cgcacgctga gggaagctgg gcccagtgtc gccgtggatt 1860 ccagcgggag gagagcgcac ttgactgtcg gccaggcggc cgcaggggga agtgggaatc 1920 tgctcactga gagaagcact ttcactgact cccagctggg gaatgcagac atggagatga 1980 ctctggagcg agcagtgagt atgctcgagg cagaccacat gctgccatcc aggatttctg 2040 ctgcagctac tttcatacag cacgagtgct tccagaaatc tgaagctcgg aagagggtta 2100 accagcttcg tggcatcctc aagcttctgc agctcctaaa agttcagaat gaagacgttc 2160 agcgagctgt gtgtggggcc ttgagaaact tagtatttga agacaatgac aacaaattgg 2220 aggtggctga actaaatggg gtacctcggc tgctccaggt gctgaagcaa accagagact 2280 tggagactaa aaaacaaata acagaccata cagtcaattt aagaagtagg aatggctggc 2340 cgggcgcggt ggctcacgcc tgtaatccca gcactttggg aggccaaggc gggcggatca 2400 cgaggtcagg agttcgagac cagcctgacc aacatggttt gctgtggaat ttgtcatcta 2460 atgacaaact caagaatctc atgataacag aagcattgct tacgctgacg gagaatatca 2520 tcatcccctt ttctgggtgg cctgaaggag actacccaaa agcaaatggt ttgctcgatt 2580 ttgacatatt ctacaacgtc actggatgcc taagaaacat gagttctgct ggcgctgatg 2640 ggagaaaagc gatgagaaga tgtgacggac tcattgactc actggtccat tatgtcagag 2700 gaaccattgc agattaccag ccagatgaca aggccacgga gaattgtgtg tgcattcttc 2760 ataacctctc ctaccagctg gaggcagagc tcccagagaa atattcccag aatatctata 2820 ttcaaaaccg gaatatccag actgacaaca acaaaagtat tggatgtttt ggcagtcgaa 2880 gcaggaaagt aaaagagcaa taccaggacg tgccgatgcc ggaggaaaag agcaacccca 2940 agggcgtgga gtggctgtgg cattccattg ttataaggat gtatctgtcc ttgatcgcca 3000 aaagtgtccg caactacaca caagaagcat ccttaggagc tctgcagaac ctcacggccg 3060 gaagtggacc aatgccgaca tcagtggctc agacagttgt ccagaaggaa agtggcctgc 3120 agcacacccg aaagatgctg catgttggtg acccaagtgt gaaaaagaca gccatctcgc 3180 tgctgaggaa tctgtcccgg aatctttctc tgcagaatga aattgccaaa gaaactctcc 3240 ctgatttggt ttccatcatt cctgacacag tcccgagtac tgaccttctc attgaaacta 3300 cagcctctgc ctgttacaca ttgaacaaca taatccaaaa cagttaccag aatgcacgcg 3360 accttctaaa caccgggggc atccagaaaa ttatggccat tagtgcaggc gatgcctatg 3420 cctccaacaa agcaagtaaa gctgcttccg tccttctgta ttctctgtgg gcacacacgg 3480 aactgcatca tgcctacaag aaggctcagt ttaagaagac agattttgtc aacagccgga 3540 ctgccaaagc ctaccactcc cttaaagact gatcaacctc tggattacaa aatttgtgaa 3600 agattgactg gtattcttaa ctatgttgct ccttttacgc tatgtggata cgctgcttta 3660 atgcctttgt atcatgctat tgcttcccgt atggctttca ttttctcctc cttgtataaa 3720 tcctggttgc tgtctcttta tgaggagttg tggcccgttg tcaggcaacg tggcgtggtg 3780 tgcactgtgt ttgctgacgc aacccccact ggttggggca ttgccaccac ctgtcagctc 3840 ctttccggga ctttcgcttt ccccctccct attgccacgg cggaactcat cgccgcctgc 3900 cttgcccgct gctggacagg ggctcggctg ttgggcactg acaattccgt ggtgttgtcg 3960 gggaaatcat cgtcctttcc ttggctgctc gcctgtgttg ccacctggat tctgcgcggg 4020 acgtccttct gctacgtccc ttcggccctc aatccagcgg accttccttc ccgcggcctg 4080 ctgccggctc tgcggcctct tccgcgtctt cgccttcgcc ctcagacgag tcggatctcc 4140 ctttgggccg cctccccgca tcattgcctg cccgggtggc atccctgtga cccctcccca 4200 gtgcctctcc tggccctgga agttgccact ccagtgccca ccagccttgt cctaataaaa 4260 ttaagttgca tcattttgtc tgactaggtg tccttctata atattatggg gtggaggggg 4320 gtggtatgga gcaaggggcc caagttggga agaaacctgt agggcctgc 4369 <210> SEQ ID NO 96 <211> LENGTH: 3993 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Made in Lab - expression cassette polynucleotide <400> SEQUENCE: 96 ctcagtccat taggagccag tagcctggaa gatgtcttta cccccagcat cagttcaagt 60 ggagcagcac ataactcttg ccctctgcct tccaagattc tggtgctgag acttatggag 120 tgtcttggag gttgccttct gccccccaac cctgctccca gctggccctc ccaggcctgg 180 gttgctggcc tctgctttat caggattctc aagagggaca gctggtttat gttgcatgac 240 tgttccctgc atatctgctc tggttttaaa tagcttatct gagcagctgg aggaccacat 300 gggcttatat ggcgtggggt acatgttcct gtagccttgt ccctggcacc tgccaaaata 360 gcagccaaca ccccccaccc ccaccgccat ccccctgccc cacccgtccc ctgtcgcaca 420 ttcctccctc cgcagggctg gctcaccagg ccccagccca catgcctgct taaagccctc 480 tccatcctct gcctcaccca gtccccgctg agactgagca gacgcctcca ggatctgtcg 540 gcaggccacc atggcagccc ccggcgcccc agctgagtac ggctacatcc ggaccgtcct 600 gggccagcag atcctgggac aactggacag ctccagcctg gcgctgccct ccgaggccaa 660 gctgaagctg gcggggagca gcggccgcgg cggccagaca gtcaagagcc tgcggatcca 720 ggagcaggtg cagcagaccc tcgcccggaa gggccgcagc tccgtgggca acggaaatct 780 tcaccgaacc agcagtgttc ctgagtatgt ctacaaccta cacttggttg aaaatgattt 840 tgttggaggc cgttcccctg ttcctaaaac ctatgacatg ctaaaggctg gcacaactgc 900 cacttatgaa ggtcgctggg gaagaggaac agcacagtac agctcccaga agtccgtgga 960 agaaaggtcc ttgaggcatc ctctgaggag actggagatt tctcctgaca gcagcccgga 1020 gagggctcac tacacgcaca gcgattacca gtacagccag agaagccagg ctgggcacac 1080 cctgcaccac caagaaagca ggcgggccgc cctcctagtg ccaccgagat atgctcgttc 1140 cgagatcgtg ggggtcagcc gtgctggcac cacaagcagg cagcgccact ttgacacata 1200 ccacagacag taccagcatg gctctgttag cgacaccgtt tttgacagca tccctgccaa 1260 cccggccctg ctcacgtacc ccaggccagg gaccagccgc agcatgggca acctcttgga 1320 gaaggagaac tacctgacgg cagggctcac tgtcgggcag gtcaggccgc tggtgcccct 1380 gcagcccgtc actcagaaca gggcttccag gtcctcctgg catcagagct ccttccacag 1440 cacccgcacg ctgagggaag ctgggcccag tgtcgccgtg gattccagcg ggaggagagc 1500 gcacttgact gtcggccagg cggccgcagg gggaagtggg aatctgctca ctgagagaag 1560 cactttcact gactcccagc tggggaatgc agacatggag atgactctgg agcgagcagt 1620 gagtatgctc gaggcagacc acatgctgcc atccaggatt tctgctgcag ctactttcat 1680 acagcacgag tgcttccaga aatctgaagc tcggaagagg gttaaccagc ttcgtggcat 1740 cctcaagctt ctgcagctcc taaaagttca gaatgaagac gttcagcgag ctgtgtgtgg 1800 ggccttgaga aacttagtat ttgaagacaa tgacaacaaa ttggaggtgg ctgaactaaa 1860 tggggtacct cggctgctcc aggtgctgaa gcaaaccaga gacttggaga ctaaaaaaca 1920 aataacagac catacagtca atttaagaag taggaatggc tggccgggcg cggtggctca 1980 cgcctgtaat cccagcactt tgggaggcca aggcgggcgg atcacgaggt caggagttcg 2040 agaccagcct gaccaacatg gtttgctgtg gaatttgtca tctaatgaca aactcaagaa 2100 tctcatgata acagaagcat tgcttacgct gacggagaat atcatcatcc ccttttctgg 2160 gtggcctgaa ggagactacc caaaagcaaa tggtttgctc gattttgaca tattctacaa 2220 cgtcactgga tgcctaagaa acatgagttc tgctggcgct gatgggagaa aagcgatgag 2280 aagatgtgac ggactcattg actcactggt ccattatgtc agaggaacca ttgcagatta 2340 ccagccagat gacaaggcca cggagaattg tgtgtgcatt cttcataacc tctcctacca 2400 gctggaggca gagctcccag agaaatattc ccagaatatc tatattcaaa accggaatat 2460 ccagactgac aacaacaaaa gtattggatg ttttggcagt cgaagcagga aagtaaaaga 2520 gcaataccag gacgtgccga tgccggagga aaagagcaac cccaagggcg tggagtggct 2580 gtggcattcc attgttataa ggatgtatct gtccttgatc gccaaaagtg tccgcaacta 2640 cacacaagaa gcatccttag gagctctgca gaacctcacg gccggaagtg gaccaatgcc 2700 gacatcagtg gctcagacag ttgtccagaa ggaaagtggc ctgcagcaca cccgaaagat 2760 gctgcatgtt ggtgacccaa gtgtgaaaaa gacagccatc tcgctgctga ggaatctgtc 2820 ccggaatctt tctctgcaga atgaaattgc caaagaaact ctccctgatt tggtttccat 2880 cattcctgac acagtcccga gtactgacct tctcattgaa actacagcct ctgcctgtta 2940 cacattgaac aacataatcc aaaacagtta ccagaatgca cgcgaccttc taaacaccgg 3000 gggcatccag aaaattatgg ccattagtgc aggcgatgcc tatgcctcca acaaagcaag 3060 taaagctgct tccgtccttc tgtattctct gtgggcacac acggaactgc atcatgccta 3120 caagaaggct cagtttaaga agacagattt tgtcaacagc cggactgcca aagcctacca 3180 ctcccttaaa gactgatcaa cctctggatt acaaaatttg tgaaagattg actggtattc 3240 ttaactatgt tgctcctttt acgctatgtg gatacgctgc tttaatgcct ttgtatcatg 3300 ctattgcttc ccgtatggct ttcattttct cctccttgta taaatcctgg ttgctgtctc 3360 tttatgagga gttgtggccc gttgtcaggc aacgtggcgt ggtgtgcact gtgtttgctg 3420 acgcaacccc cactggttgg ggcattgcca ccacctgtca gctcctttcc gggactttcg 3480 ctttccccct ccctattgcc acggcggaac tcatcgccgc ctgccttgcc cgctgctgga 3540 caggggctcg gctgttgggc actgacaatt ccgtggtgtt gtcggggaaa tcatcgtcct 3600 ttccttggct gctcgcctgt gttgccacct ggattctgcg cgggacgtcc ttctgctacg 3660 tcccttcggc cctcaatcca gcggaccttc cttcccgcgg cctgctgccg gctctgcggc 3720 ctcttccgcg tcttcgcctt cgccctcaga cgagtcggat ctccctttgg gccgcctccc 3780 cgcatcattg cctgcccggg tggcatccct gtgacccctc cccagtgcct ctcctggccc 3840 tggaagttgc cactccagtg cccaccagcc ttgtcctaat aaaattaagt tgcatcattt 3900 tgtctgacta ggtgtccttc tataatatta tggggtggag gggggtggta tggagcaagg 3960 ggcccaagtt gggaagaaac ctgtagggcc tgc 3993

1 SEQUENCE LISTING <160> NUMBER OF SEQ ID NOS: 96 <210> SEQ ID NO 1 <211> LENGTH: 837 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 1 Met Ala Ala Pro Gly Ala Pro Ala Glu Tyr Gly Tyr Ile Arg Thr Val 1 5 10 15 Leu Gly Gln Gln Ile Leu Gly Gln Leu Asp Ser Ser Ser Leu Ala Leu 20 25 30 Pro Ser Glu Ala Lys Leu Lys Leu Ala Gly Ser Ser Gly Arg Gly Gly 35 40 45 Gln Thr Val Lys Ser Leu Arg Ile Gln Glu Gln Val Gln Gln Thr Leu 50 55 60 Ala Arg Lys Gly Arg Ser Ser Val Gly Asn Gly Asn Leu His Arg Thr 65 70 75 80 Ser Ser Val Pro Glu Tyr Val Tyr Asn Leu His Leu Val Glu Asn Asp 85 90 95 Phe Val Gly Gly Arg Ser Pro Val Pro Lys Thr Tyr Asp Met Leu Lys 100 105 110 Ala Gly Thr Thr Ala Thr Tyr Glu Gly Arg Trp Gly Arg Gly Thr Ala 115 120 125 Gln Tyr Ser Ser Gln Lys Ser Val Glu Glu Arg Ser Leu Arg His Pro 130 135 140 Leu Arg Arg Leu Glu Ile Ser Pro Asp Ser Ser Pro Glu Arg Ala His 145 150 155 160 Tyr Thr His Ser Asp Tyr Gln Tyr Ser Gln Arg Ser Gln Ala Gly His 165 170 175 Thr Leu His His Gln Glu Ser Arg Arg Ala Ala Leu Leu Val Pro Pro 180 185 190 Arg Tyr Ala Arg Ser Glu Ile Val Gly Val Ser Arg Ala Gly Thr Thr 195 200 205 Ser Arg Gln Arg His Phe Asp Thr Tyr His Arg Gln Tyr Gln His Gly 210 215 220 Ser Val Ser Asp Thr Val Phe Asp Ser Ile Pro Ala Asn Pro Ala Leu 225 230 235 240 Leu Thr Tyr Pro Arg Pro Gly Thr Ser Arg Ser Met Gly Asn Leu Leu 245 250 255 Glu Lys Glu Asn Tyr Leu Thr Ala Gly Leu Thr Val Gly Gln Val Arg 260 265 270 Pro Leu Val Pro Leu Gln Pro Val Thr Gln Asn Arg Ala Ser Arg Ser 275 280 285 Ser Trp His Gln Ser Ser Phe His Ser Thr Arg Thr Leu Arg Glu Ala 290 295 300 Gly Pro Ser Val Ala Val Asp Ser Ser Gly Arg Arg Ala His Leu Thr 305 310 315 320 Val Gly Gln Ala Ala Ala Gly Gly Ser Gly Asn Leu Leu Thr Glu Arg 325 330 335 Ser Thr Phe Thr Asp Ser Gln Leu Gly Asn Ala Asp Met Glu Met Thr 340 345 350 Leu Glu Arg Ala Val Ser Met Leu Glu Ala Asp His Met Leu Pro Ser 355 360 365 Arg Ile Ser Ala Ala Ala Thr Phe Ile Gln His Glu Cys Phe Gln Lys 370 375 380 Ser Glu Ala Arg Lys Arg Val Asn Gln Leu Arg Gly Ile Leu Lys Leu 385 390 395 400 Leu Gln Leu Leu Lys Val Gln Asn Glu Asp Val Gln Arg Ala Val Cys 405 410 415 Gly Ala Leu Arg Asn Leu Val Phe Glu Asp Asn Asp Asn Lys Leu Glu 420 425 430 Val Ala Glu Leu Asn Gly Val Pro Arg Leu Leu Gln Val Leu Lys Gln 435 440 445 Thr Arg Asp Leu Glu Thr Lys Lys Gln Ile Thr Gly Leu Leu Trp Asn 450 455 460 Leu Ser Ser Asn Asp Lys Leu Lys Asn Leu Met Ile Thr Glu Ala Leu 465 470 475 480 Leu Thr Leu Thr Glu Asn Ile Ile Ile Pro Phe Ser Gly Trp Pro Glu 485 490 495 Gly Asp Tyr Pro Lys Ala Asn Gly Leu Leu Asp Phe Asp Ile Phe Tyr 500 505 510 Asn Val Thr Gly Cys Leu Arg Asn Met Ser Ser Ala Gly Ala Asp Gly 515 520 525 Arg Lys Ala Met Arg Arg Cys Asp Gly Leu Ile Asp Ser Leu Val His 530 535 540 Tyr Val Arg Gly Thr Ile Ala Asp Tyr Gln Pro Asp Asp Lys Ala Thr 545 550 555 560 Glu Asn Cys Val Cys Ile Leu His Asn Leu Ser Tyr Gln Leu Glu Ala 565 570 575 Glu Leu Pro Glu Lys Tyr Ser Gln Asn Ile Tyr Ile Gln Asn Arg Asn 580 585 590 Ile Gln Thr Asp Asn Asn Lys Ser Ile Gly Cys Phe Gly Ser Arg Ser 595 600 605 Arg Lys Val Lys Glu Gln Tyr Gln Asp Val Pro Met Pro Glu Glu Lys 610 615 620 Ser Asn Pro Lys Gly Val Glu Trp Leu Trp His Ser Ile Val Ile Arg 625 630 635 640 Met Tyr Leu Ser Leu Ile Ala Lys Ser Val Arg Asn Tyr Thr Gln Glu 645 650 655 Ala Ser Leu Gly Ala Leu Gln Asn Leu Thr Ala Gly Ser Gly Pro Met 660 665 670 Pro Thr Ser Val Ala Gln Thr Val Val Gln Lys Glu Ser Gly Leu Gln 675 680 685 His Thr Arg Lys Met Leu His Val Gly Asp Pro Ser Val Lys Lys Thr 690 695 700 Ala Ile Ser Leu Leu Arg Asn Leu Ser Arg Asn Leu Ser Leu Gln Asn 705 710 715 720 Glu Ile Ala Lys Glu Thr Leu Pro Asp Leu Val Ser Ile Ile Pro Asp 725 730 735 Thr Val Pro Ser Thr Asp Leu Leu Ile Glu Thr Thr Ala Ser Ala Cys 740 745 750 Tyr Thr Leu Asn Asn Ile Ile Gln Asn Ser Tyr Gln Asn Ala Arg Asp 755 760 765 Leu Leu Asn Thr Gly Gly Ile Gln Lys Ile Met Ala Ile Ser Ala Gly 770 775 780 Asp Ala Tyr Ala Ser Asn Lys Ala Ser Lys Ala Ala Ser Val Leu Leu 785 790 795 800 Tyr Ser Leu Trp Ala His Thr Glu Leu His His Ala Tyr Lys Lys Ala 805 810 815 Gln Phe Lys Lys Thr Asp Phe Val Asn Ser Arg Thr Ala Lys Ala Tyr 820 825 830 His Ser Leu Lys Asp 835 <210> SEQ ID NO 2 <211> LENGTH: 881 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <400> SEQUENCE: 2 Met Ala Ala Pro Gly Ala Pro Ala Glu Tyr Gly Tyr Ile Arg Thr Val 1 5 10 15 Leu Gly Gln Gln Ile Leu Gly Gln Leu Asp Ser Ser Ser Leu Ala Leu 20 25 30 Pro Ser Glu Ala Lys Leu Lys Leu Ala Gly Ser Ser Gly Arg Gly Gly 35 40 45 Gln Thr Val Lys Ser Leu Arg Ile Gln Glu Gln Val Gln Gln Thr Leu 50 55 60 Ala Arg Lys Gly Arg Ser Ser Val Gly Asn Gly Asn Leu His Arg Thr 65 70 75 80 Ser Ser Val Pro Glu Tyr Val Tyr Asn Leu His Leu Val Glu Asn Asp 85 90 95 Phe Val Gly Gly Arg Ser Pro Val Pro Lys Thr Tyr Asp Met Leu Lys 100 105 110 Ala Gly Thr Thr Ala Thr Tyr Glu Gly Arg Trp Gly Arg Gly Thr Ala 115 120 125 Gln Tyr Ser Ser Gln Lys Ser Val Glu Glu Arg Ser Leu Arg His Pro 130 135 140 Leu Arg Arg Leu Glu Ile Ser Pro Asp Ser Ser Pro Glu Arg Ala His 145 150 155 160 Tyr Thr His Ser Asp Tyr Gln Tyr Ser Gln Arg Ser Gln Ala Gly His 165 170 175 Thr Leu His His Gln Glu Ser Arg Arg Ala Ala Leu Leu Val Pro Pro 180 185 190 Arg Tyr Ala Arg Ser Glu Ile Val Gly Val Ser Arg Ala Gly Thr Thr 195 200 205 Ser Arg Gln Arg His Phe Asp Thr Tyr His Arg Gln Tyr Gln His Gly 210 215 220 Ser Val Ser Asp Thr Val Phe Asp Ser Ile Pro Ala Asn Pro Ala Leu 225 230 235 240 Leu Thr Tyr Pro Arg Pro Gly Thr Ser Arg Ser Met Gly Asn Leu Leu 245 250 255 Glu Lys Glu Asn Tyr Leu Thr Ala Gly Leu Thr Val Gly Gln Val Arg 260 265 270 Pro Leu Val Pro Leu Gln Pro Val Thr Gln Asn Arg Ala Ser Arg Ser 275 280 285 Ser Trp His Gln Ser Ser Phe His Ser Thr Arg Thr Leu Arg Glu Ala 290 295 300 Gly Pro Ser Val Ala Val Asp Ser Ser Gly Arg Arg Ala His Leu Thr 305 310 315 320 Val Gly Gln Ala Ala Ala Gly Gly Ser Gly Asn Leu Leu Thr Glu Arg 325 330 335 Ser Thr Phe Thr Asp Ser Gln Leu Gly Asn Ala Asp Met Glu Met Thr 340 345 350 Leu Glu Arg Ala Val Ser Met Leu Glu Ala Asp His Met Leu Pro Ser 355 360 365 Arg Ile Ser Ala Ala Ala Thr Phe Ile Gln His Glu Cys Phe Gln Lys

370 375 380 Ser Glu Ala Arg Lys Arg Val Asn Gln Leu Arg Gly Ile Leu Lys Leu 385 390 395 400 Leu Gln Leu Leu Lys Val Gln Asn Glu Asp Val Gln Arg Ala Val Cys 405 410 415 Gly Ala Leu Arg Asn Leu Val Phe Glu Asp Asn Asp Asn Lys Leu Glu 420 425 430 Val Ala Glu Leu Asn Gly Val Pro Arg Leu Leu Gln Val Leu Lys Gln 435 440 445 Thr Arg Asp Leu Glu Thr Lys Lys Gln Ile Thr Asp His Thr Val Asn 450 455 460 Leu Arg Ser Arg Asn Gly Trp Pro Gly Ala Val Ala His Ala Cys Asn 465 470 475 480 Pro Ser Thr Leu Gly Gly Gln Gly Gly Arg Ile Thr Arg Ser Gly Val 485 490 495 Arg Asp Gln Pro Asp Gln His Gly Leu Leu Trp Asn Leu Ser Ser Asn 500 505 510 Asp Lys Leu Lys Asn Leu Met Ile Thr Glu Ala Leu Leu Thr Leu Thr 515 520 525 Glu Asn Ile Ile Ile Pro Phe Ser Gly Trp Pro Glu Gly Asp Tyr Pro 530 535 540 Lys Ala Asn Gly Leu Leu Asp Phe Asp Ile Phe Tyr Asn Val Thr Gly 545 550 555 560 Cys Leu Arg Asn Met Ser Ser Ala Gly Ala Asp Gly Arg Lys Ala Met 565 570 575 Arg Arg Cys Asp Gly Leu Ile Asp Ser Leu Val His Tyr Val Arg Gly 580 585 590 Thr Ile Ala Asp Tyr Gln Pro Asp Asp Lys Ala Thr Glu Asn Cys Val 595 600 605 Cys Ile Leu His Asn Leu Ser Tyr Gln Leu Glu Ala Glu Leu Pro Glu 610 615 620 Lys Tyr Ser Gln Asn Ile Tyr Ile Gln Asn Arg Asn Ile Gln Thr Asp 625 630 635 640 Asn Asn Lys Ser Ile Gly Cys Phe Gly Ser Arg Ser Arg Lys Val Lys 645 650 655 Glu Gln Tyr Gln Asp Val Pro Met Pro Glu Glu Lys Ser Asn Pro Lys 660 665 670 Gly Val Glu Trp Leu Trp His Ser Ile Val Ile Arg Met Tyr Leu Ser 675 680 685 Leu Ile Ala Lys Ser Val Arg Asn Tyr Thr Gln Glu Ala Ser Leu Gly 690 695 700 Ala Leu Gln Asn Leu Thr Ala Gly Ser Gly Pro Met Pro Thr Ser Val 705 710 715 720 Ala Gln Thr Val Val Gln Lys Glu Ser Gly Leu Gln His Thr Arg Lys 725 730 735 Met Leu His Val Gly Asp Pro Ser Val Lys Lys Thr Ala Ile Ser Leu 740 745 750 Leu Arg Asn Leu Ser Arg Asn Leu Ser Leu Gln Asn Glu Ile Ala Lys 755 760 765 Glu Thr Leu Pro Asp Leu Val Ser Ile Ile Pro Asp Thr Val Pro Ser 770 775 780 Thr Asp Leu Leu Ile Glu Thr Thr Ala Ser Ala Cys Tyr Thr Leu Asn 785 790 795 800 Asn Ile Ile Gln Asn Ser Tyr Gln Asn Ala Arg Asp Leu Leu Asn Thr 805 810 815 Gly Gly Ile Gln Lys Ile Met Ala Ile Ser Ala Gly Asp Ala Tyr Ala 820 825 830 Ser Asn Lys Ala Ser Lys Ala Ala Ser Val Leu Leu Tyr Ser Leu Trp 835 840 845 Ala His Thr Glu Leu His His Ala Tyr Lys Lys Ala Gln Phe Lys Lys 850 855 860 Thr Asp Phe Val Asn Ser Arg Thr Ala Lys Ala Tyr His Ser Leu Lys 865 870 875 880 Asp <210> SEQ ID NO 3 <211> LENGTH: 2511 <212> TYPE: DNA <213> ORGANISM: Homo sapiens <400> SEQUENCE: 3 atggcagccc ccggcgcccc agctgagtac ggctacatcc ggaccgtcct gggccagcag 60 atcctgggac aactggacag ctccagcctg gcgctgccct ccgaggccaa gctgaagctg 120 gcggggagca gcggccgcgg cggccagaca gtcaagagcc tgcggatcca ggagcaggtg 180 cagcagaccc tcgcccggaa gggccgcagc tccgtgggca acggaaatct tcaccgaacc 240 agcagtgttc ctgagtatgt ctacaaccta cacttggttg aaaatgattt tgttggaggc 300 cgttcccctg ttcctaaaac ctatgacatg ctaaaggctg gcacaactgc cacttatgaa 360 ggtcgctggg gaagaggaac agcacagtac agctcccaga agtccgtgga agaaaggtcc 420 ttgaggcatc ctctgaggag actggagatt tctcctgaca gcagcccgga gagggctcac 480 tacacgcaca gcgattacca gtacagccag agaagccagg ctgggcacac cctgcaccac 540 caagaaagca ggcgggccgc cctcctagtg ccaccgagat atgctcgttc cgagatcgtg 600 ggggtcagcc gtgctggcac cacaagcagg cagcgccact ttgacacata ccacagacag 660 taccagcatg gctctgttag cgacaccgtt tttgacagca tccctgccaa cccggccctg 720 ctcacgtacc ccaggccagg gaccagccgc agcatgggca acctcttgga gaaggagaac 780 tacctgacgg cagggctcac tgtcgggcag gtcaggccgc tggtgcccct gcagcccgtc 840 actcagaaca gggcttccag gtcctcctgg catcagagct ccttccacag cacccgcacg 900 ctgagggaag ctgggcccag tgtcgccgtg gattccagcg ggaggagagc gcacttgact 960 gtcggccagg cggccgcagg gggaagtggg aatctgctca ctgagagaag cactttcact 1020 gactcccagc tggggaatgc agacatggag atgactctgg agcgagcagt gagtatgctc 1080 gaggcagacc acatgctgcc atccaggatt tctgctgcag ctactttcat acagcacgag 1140 tgcttccaga aatctgaagc tcggaagagg gttaaccagc ttcgtggcat cctcaagctt 1200 ctgcagctcc taaaagttca gaatgaagac gttcagcgag ctgtgtgtgg ggccttgaga 1260 aacttagtat ttgaagacaa tgacaacaaa ttggaggtgg ctgaactaaa tggggtacct 1320 cggctgctcc aggtgctgaa gcaaaccaga gacttggaga ctaaaaaaca aataacaggt 1380 ttgctgtgga atttgtcatc taatgacaaa ctcaagaatc tcatgataac agaagcattg 1440 cttacgctga cggagaatat catcatcccc ttttctgggt ggcctgaagg agactaccca 1500 aaagcaaatg gtttgctcga ttttgacata ttctacaacg tcactggatg cctaagaaac 1560 atgagttctg ctggcgctga tgggagaaaa gcgatgagaa gatgtgacgg actcattgac 1620 tcactggtcc attatgtcag aggaaccatt gcagattacc agccagatga caaggccacg 1680 gagaattgtg tgtgcattct tcataacctc tcctaccagc tggaggcaga gctcccagag 1740 aaatattccc agaatatcta tattcaaaac cggaatatcc agactgacaa caacaaaagt 1800 attggatgtt ttggcagtcg aagcaggaaa gtaaaagagc aataccagga cgtgccgatg 1860 ccggaggaaa agagcaaccc caagggcgtg gagtggctgt ggcattccat tgttataagg 1920 atgtatctgt ccttgatcgc caaaagtgtc cgcaactaca cacaagaagc atccttagga 1980 gctctgcaga acctcacggc cggaagtgga ccaatgccga catcagtggc tcagacagtt 2040 gtccagaagg aaagtggcct gcagcacacc cgaaagatgc tgcatgttgg tgacccaagt 2100 gtgaaaaaga cagccatctc gctgctgagg aatctgtccc ggaatctttc tctgcagaat 2160 gaaattgcca aagaaactct ccctgatttg gtttccatca ttcctgacac agtcccgagt 2220 actgaccttc tcattgaaac tacagcctct gcctgttaca cattgaacaa cataatccaa 2280 aacagttacc agaatgcacg cgaccttcta aacaccgggg gcatccagaa aattatggcc 2340 attagtgcag gcgatgccta tgcctccaac aaagcaagta aagctgcttc cgtccttctg 2400 tattctctgt gggcacacac ggaactgcat catgcctaca agaaggctca gtttaagaag 2460 acagattttg tcaacagccg gactgccaaa gcctaccact cccttaaaga c 2511 <210> SEQ ID NO 4 <211> LENGTH: 2643 <212> TYPE: DNA <213> ORGANISM: Homo sapiens <400> SEQUENCE: 4 atggcagccc ccggcgcccc agctgagtac ggctacatcc ggaccgtcct gggccagcag 60 atcctgggac aactggacag ctccagcctg gcgctgccct ccgaggccaa gctgaagctg 120 gcggggagca gcggccgcgg cggccagaca gtcaagagcc tgcggatcca ggagcaggtg 180 cagcagaccc tcgcccggaa gggccgcagc tccgtgggca acggaaatct tcaccgaacc 240 agcagtgttc ctgagtatgt ctacaaccta cacttggttg aaaatgattt tgttggaggc 300 cgttcccctg ttcctaaaac ctatgacatg ctaaaggctg gcacaactgc cacttatgaa 360 ggtcgctggg gaagaggaac agcacagtac agctcccaga agtccgtgga agaaaggtcc 420 ttgaggcatc ctctgaggag actggagatt tctcctgaca gcagcccgga gagggctcac 480 tacacgcaca gcgattacca gtacagccag agaagccagg ctgggcacac cctgcaccac 540 caagaaagca ggcgggccgc cctcctagtg ccaccgagat atgctcgttc cgagatcgtg 600 ggggtcagcc gtgctggcac cacaagcagg cagcgccact ttgacacata ccacagacag 660 taccagcatg gctctgttag cgacaccgtt tttgacagca tccctgccaa cccggccctg 720 ctcacgtacc ccaggccagg gaccagccgc agcatgggca acctcttgga gaaggagaac 780 tacctgacgg cagggctcac tgtcgggcag gtcaggccgc tggtgcccct gcagcccgtc 840 actcagaaca gggcttccag gtcctcctgg catcagagct ccttccacag cacccgcacg 900 ctgagggaag ctgggcccag tgtcgccgtg gattccagcg ggaggagagc gcacttgact 960 gtcggccagg cggccgcagg gggaagtggg aatctgctca ctgagagaag cactttcact 1020 gactcccagc tggggaatgc agacatggag atgactctgg agcgagcagt gagtatgctc 1080 gaggcagacc acatgctgcc atccaggatt tctgctgcag ctactttcat acagcacgag 1140 tgcttccaga aatctgaagc tcggaagagg gttaaccagc ttcgtggcat cctcaagctt 1200 ctgcagctcc taaaagttca gaatgaagac gttcagcgag ctgtgtgtgg ggccttgaga 1260 aacttagtat ttgaagacaa tgacaacaaa ttggaggtgg ctgaactaaa tggggtacct 1320 cggctgctcc aggtgctgaa gcaaaccaga gacttggaga ctaaaaaaca aataacagac 1380 catacagtca atttaagaag taggaatggc tggccgggcg cggtggctca cgcctgtaat 1440 cccagcactt tgggaggcca aggcgggcgg atcacgaggt caggagttcg agaccagcct 1500 gaccaacatg gtttgctgtg gaatttgtca tctaatgaca aactcaagaa tctcatgata 1560 acagaagcat tgcttacgct gacggagaat atcatcatcc ccttttctgg gtggcctgaa 1620

ggagactacc caaaagcaaa tggtttgctc gattttgaca tattctacaa cgtcactgga 1680 tgcctaagaa acatgagttc tgctggcgct gatgggagaa aagcgatgag aagatgtgac 1740 ggactcattg actcactggt ccattatgtc agaggaacca ttgcagatta ccagccagat 1800 gacaaggcca cggagaattg tgtgtgcatt cttcataacc tctcctacca gctggaggca 1860 gagctcccag agaaatattc ccagaatatc tatattcaaa accggaatat ccagactgac 1920 aacaacaaaa gtattggatg ttttggcagt cgaagcagga aagtaaaaga gcaataccag 1980 gacgtgccga tgccggagga aaagagcaac cccaagggcg tggagtggct gtggcattcc 2040 attgttataa ggatgtatct gtccttgatc gccaaaagtg tccgcaacta cacacaagaa 2100 gcatccttag gagctctgca gaacctcacg gccggaagtg gaccaatgcc gacatcagtg 2160 gctcagacag ttgtccagaa ggaaagtggc ctgcagcaca cccgaaagat gctgcatgtt 2220 ggtgacccaa gtgtgaaaaa gacagccatc tcgctgctga ggaatctgtc ccggaatctt 2280 tctctgcaga atgaaattgc caaagaaact ctccctgatt tggtttccat cattcctgac 2340 acagtcccga gtactgacct tctcattgaa actacagcct ctgcctgtta cacattgaac 2400 aacataatcc aaaacagtta ccagaatgca cgcgaccttc taaacaccgg gggcatccag 2460 aaaattatgg ccattagtgc aggcgatgcc tatgcctcca acaaagcaag taaagctgct 2520 tccgtccttc tgtattctct gtgggcacac acggaactgc atcatgccta caagaaggct 2580 cagtttaaga agacagattt tgtcaacagc cggactgcca aagcctacca ctcccttaaa 2640 gac 2643 <210> SEQ ID NO 5 <211> LENGTH: 10 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Kozak sequence motif <400> SEQUENCE: 5 gccaccatgg 10 <210> SEQ ID NO 6 <211> LENGTH: 2517 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Polynucleotide encoding an PKP2a with Kozak sequence <400> SEQUENCE: 6 gccaccatgg cagcccccgg cgccccagct gagtacggct acatccggac cgtcctgggc 60 cagcagatcc tgggacaact ggacagctcc agcctggcgc tgccctccga ggccaagctg 120 aagctggcgg ggagcagcgg ccgcggcggc cagacagtca agagcctgcg gatccaggag 180 caggtgcagc agaccctcgc ccggaagggc cgcagctccg tgggcaacgg aaatcttcac 240 cgaaccagca gtgttcctga gtatgtctac aacctacact tggttgaaaa tgattttgtt 300 ggaggccgtt cccctgttcc taaaacctat gacatgctaa aggctggcac aactgccact 360 tatgaaggtc gctggggaag aggaacagca cagtacagct cccagaagtc cgtggaagaa 420 aggtccttga ggcatcctct gaggagactg gagatttctc ctgacagcag cccggagagg 480 gctcactaca cgcacagcga ttaccagtac agccagagaa gccaggctgg gcacaccctg 540 caccaccaag aaagcaggcg ggccgccctc ctagtgccac cgagatatgc tcgttccgag 600 atcgtggggg tcagccgtgc tggcaccaca agcaggcagc gccactttga cacataccac 660 agacagtacc agcatggctc tgttagcgac accgtttttg acagcatccc tgccaacccg 720 gccctgctca cgtaccccag gccagggacc agccgcagca tgggcaacct cttggagaag 780 gagaactacc tgacggcagg gctcactgtc gggcaggtca ggccgctggt gcccctgcag 840 cccgtcactc agaacagggc ttccaggtcc tcctggcatc agagctcctt ccacagcacc 900 cgcacgctga gggaagctgg gcccagtgtc gccgtggatt ccagcgggag gagagcgcac 960 ttgactgtcg gccaggcggc cgcaggggga agtgggaatc tgctcactga gagaagcact 1020 ttcactgact cccagctggg gaatgcagac atggagatga ctctggagcg agcagtgagt 1080 atgctcgagg cagaccacat gctgccatcc aggatttctg ctgcagctac tttcatacag 1140 cacgagtgct tccagaaatc tgaagctcgg aagagggtta accagcttcg tggcatcctc 1200 aagcttctgc agctcctaaa agttcagaat gaagacgttc agcgagctgt gtgtggggcc 1260 ttgagaaact tagtatttga agacaatgac aacaaattgg aggtggctga actaaatggg 1320 gtacctcggc tgctccaggt gctgaagcaa accagagact tggagactaa aaaacaaata 1380 acaggtttgc tgtggaattt gtcatctaat gacaaactca agaatctcat gataacagaa 1440 gcattgctta cgctgacgga gaatatcatc atcccctttt ctgggtggcc tgaaggagac 1500 tacccaaaag caaatggttt gctcgatttt gacatattct acaacgtcac tggatgccta 1560 agaaacatga gttctgctgg cgctgatggg agaaaagcga tgagaagatg tgacggactc 1620 attgactcac tggtccatta tgtcagagga accattgcag attaccagcc agatgacaag 1680 gccacggaga attgtgtgtg cattcttcat aacctctcct accagctgga ggcagagctc 1740 ccagagaaat attcccagaa tatctatatt caaaaccgga atatccagac tgacaacaac 1800 aaaagtattg gatgttttgg cagtcgaagc aggaaagtaa aagagcaata ccaggacgtg 1860 ccgatgccgg aggaaaagag caaccccaag ggcgtggagt ggctgtggca ttccattgtt 1920 ataaggatgt atctgtcctt gatcgccaaa agtgtccgca actacacaca agaagcatcc 1980 ttaggagctc tgcagaacct cacggccgga agtggaccaa tgccgacatc agtggctcag 2040 acagttgtcc agaaggaaag tggcctgcag cacacccgaa agatgctgca tgttggtgac 2100 ccaagtgtga aaaagacagc catctcgctg ctgaggaatc tgtcccggaa tctttctctg 2160 cagaatgaaa ttgccaaaga aactctccct gatttggttt ccatcattcc tgacacagtc 2220 ccgagtactg accttctcat tgaaactaca gcctctgcct gttacacatt gaacaacata 2280 atccaaaaca gttaccagaa tgcacgcgac cttctaaaca ccgggggcat ccagaaaatt 2340 atggccatta gtgcaggcga tgcctatgcc tccaacaaag caagtaaagc tgcttccgtc 2400 cttctgtatt ctctgtgggc acacacggaa ctgcatcatg cctacaagaa ggctcagttt 2460 aagaagacag attttgtcaa cagccggact gccaaagcct accactccct taaagac 2517 <210> SEQ ID NO 7 <211> LENGTH: 2649 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Polynucleotide encoding an PKP2b with Kozak sequence <400> SEQUENCE: 7 gccaccatgg cagcccccgg cgccccagct gagtacggct acatccggac cgtcctgggc 60 cagcagatcc tgggacaact ggacagctcc agcctggcgc tgccctccga ggccaagctg 120 aagctggcgg ggagcagcgg ccgcggcggc cagacagtca agagcctgcg gatccaggag 180 caggtgcagc agaccctcgc ccggaagggc cgcagctccg tgggcaacgg aaatcttcac 240 cgaaccagca gtgttcctga gtatgtctac aacctacact tggttgaaaa tgattttgtt 300 ggaggccgtt cccctgttcc taaaacctat gacatgctaa aggctggcac aactgccact 360 tatgaaggtc gctggggaag aggaacagca cagtacagct cccagaagtc cgtggaagaa 420 aggtccttga ggcatcctct gaggagactg gagatttctc ctgacagcag cccggagagg 480 gctcactaca cgcacagcga ttaccagtac agccagagaa gccaggctgg gcacaccctg 540 caccaccaag aaagcaggcg ggccgccctc ctagtgccac cgagatatgc tcgttccgag 600 atcgtggggg tcagccgtgc tggcaccaca agcaggcagc gccactttga cacataccac 660 agacagtacc agcatggctc tgttagcgac accgtttttg acagcatccc tgccaacccg 720 gccctgctca cgtaccccag gccagggacc agccgcagca tgggcaacct cttggagaag 780 gagaactacc tgacggcagg gctcactgtc gggcaggtca ggccgctggt gcccctgcag 840 cccgtcactc agaacagggc ttccaggtcc tcctggcatc agagctcctt ccacagcacc 900 cgcacgctga gggaagctgg gcccagtgtc gccgtggatt ccagcgggag gagagcgcac 960 ttgactgtcg gccaggcggc cgcaggggga agtgggaatc tgctcactga gagaagcact 1020 ttcactgact cccagctggg gaatgcagac atggagatga ctctggagcg agcagtgagt 1080 atgctcgagg cagaccacat gctgccatcc aggatttctg ctgcagctac tttcatacag 1140 cacgagtgct tccagaaatc tgaagctcgg aagagggtta accagcttcg tggcatcctc 1200 aagcttctgc agctcctaaa agttcagaat gaagacgttc agcgagctgt gtgtggggcc 1260 ttgagaaact tagtatttga agacaatgac aacaaattgg aggtggctga actaaatggg 1320 gtacctcggc tgctccaggt gctgaagcaa accagagact tggagactaa aaaacaaata 1380 acagaccata cagtcaattt aagaagtagg aatggctggc cgggcgcggt ggctcacgcc 1440 tgtaatccca gcactttggg aggccaaggc gggcggatca cgaggtcagg agttcgagac 1500 cagcctgacc aacatggttt gctgtggaat ttgtcatcta atgacaaact caagaatctc 1560 atgataacag aagcattgct tacgctgacg gagaatatca tcatcccctt ttctgggtgg 1620 cctgaaggag actacccaaa agcaaatggt ttgctcgatt ttgacatatt ctacaacgtc 1680 actggatgcc taagaaacat gagttctgct ggcgctgatg ggagaaaagc gatgagaaga 1740 tgtgacggac tcattgactc actggtccat tatgtcagag gaaccattgc agattaccag 1800 ccagatgaca aggccacgga gaattgtgtg tgcattcttc ataacctctc ctaccagctg 1860 gaggcagagc tcccagagaa atattcccag aatatctata ttcaaaaccg gaatatccag 1920 actgacaaca acaaaagtat tggatgtttt ggcagtcgaa gcaggaaagt aaaagagcaa 1980 taccaggacg tgccgatgcc ggaggaaaag agcaacccca agggcgtgga gtggctgtgg 2040 cattccattg ttataaggat gtatctgtcc ttgatcgcca aaagtgtccg caactacaca 2100 caagaagcat ccttaggagc tctgcagaac ctcacggccg gaagtggacc aatgccgaca 2160 tcagtggctc agacagttgt ccagaaggaa agtggcctgc agcacacccg aaagatgctg 2220 catgttggtg acccaagtgt gaaaaagaca gccatctcgc tgctgaggaa tctgtcccgg 2280 aatctttctc tgcagaatga aattgccaaa gaaactctcc ctgatttggt ttccatcatt 2340 cctgacacag tcccgagtac tgaccttctc attgaaacta cagcctctgc ctgttacaca 2400 ttgaacaaca taatccaaaa cagttaccag aatgcacgcg accttctaaa caccgggggc 2460 atccagaaaa ttatggccat tagtgcaggc gatgcctatg cctccaacaa agcaagtaaa 2520 gctgcttccg tccttctgta ttctctgtgg gcacacacgg aactgcatca tgcctacaag 2580 aaggctcagt ttaagaagac agattttgtc aacagccgga ctgccaaagc ctaccactcc 2640 cttaaagac 2649 <210> SEQ ID NO 8 <211> LENGTH: 4081 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence

<220> FEATURE: <223> OTHER INFORMATION: Made in Lab - MHCK7-PKP2a expression cassette <400> SEQUENCE: 8 acccttcaga ttaaaaataa ctgaggtaag ggcctgggta ggggaggtgg tgtgagacgc 60 tcctgtctct cctctatctg cccatcggcc ctttggggag gaggaatgtg cccaaggact 120 aaaaaaaggc catggagcca gaggggcgag ggcaacagac ctttcatggg caaaccttgg 180 ggccctgctg tctagcatgc cccactacgg gtctaggctg cccatgtaag gaggcaaggc 240 ctggggacac ccgagatgcc tggttataat taacccagac atgtggctgc cccccccccc 300 ccaacacctg ctgcctctaa aaataaccct gtccctggtg gatcccctgc atgcgaagat 360 cttcgaacaa ggctgtgggg gactgagggc aggctgtaac aggcttgggg gccagggctt 420 atacgtgcct gggactccca aagtattact gttccatgtt cccggcgaag ggccagctgt 480 cccccgccag ctagactcag cacttagttt aggaaccagt gagcaagtca gcccttgggg 540 cagcccatac aaggccatgg ggctgggcaa gctgcacgcc tgggtccggg gtgggcacgg 600 tgcccgggca acgagctgaa agctcatctg ctctcagggg cccctccctg gggacagccc 660 ctcctggcta gtcacaccct gtaggctcct ctatataacc caggggcaca ggggctgccc 720 tcattctacc accacctcca cagcacagac agacactcag gagccagcca ggccaccatg 780 gcagcccccg gcgccccagc tgagtacggc tacatccgga ccgtcctggg ccagcagatc 840 ctgggacaac tggacagctc cagcctggcg ctgccctccg aggccaagct gaagctggcg 900 gggagcagcg gccgcggcgg ccagacagtc aagagcctgc ggatccagga gcaggtgcag 960 cagaccctcg cccggaaggg ccgcagctcc gtgggcaacg gaaatcttca ccgaaccagc 1020 agtgttcctg agtatgtcta caacctacac ttggttgaaa atgattttgt tggaggccgt 1080 tcccctgttc ctaaaaccta tgacatgcta aaggctggca caactgccac ttatgaaggt 1140 cgctggggaa gaggaacagc acagtacagc tcccagaagt ccgtggaaga aaggtccttg 1200 aggcatcctc tgaggagact ggagatttct cctgacagca gcccggagag ggctcactac 1260 acgcacagcg attaccagta cagccagaga agccaggctg ggcacaccct gcaccaccaa 1320 gaaagcaggc gggccgccct cctagtgcca ccgagatatg ctcgttccga gatcgtgggg 1380 gtcagccgtg ctggcaccac aagcaggcag cgccactttg acacatacca cagacagtac 1440 cagcatggct ctgttagcga caccgttttt gacagcatcc ctgccaaccc ggccctgctc 1500 acgtacccca ggccagggac cagccgcagc atgggcaacc tcttggagaa ggagaactac 1560 ctgacggcag ggctcactgt cgggcaggtc aggccgctgg tgcccctgca gcccgtcact 1620 cagaacaggg cttccaggtc ctcctggcat cagagctcct tccacagcac ccgcacgctg 1680 agggaagctg ggcccagtgt cgccgtggat tccagcggga ggagagcgca cttgactgtc 1740 ggccaggcgg ccgcaggggg aagtgggaat ctgctcactg agagaagcac tttcactgac 1800 tcccagctgg ggaatgcaga catggagatg actctggagc gagcagtgag tatgctcgag 1860 gcagaccaca tgctgccatc caggatttct gctgcagcta ctttcataca gcacgagtgc 1920 ttccagaaat ctgaagctcg gaagagggtt aaccagcttc gtggcatcct caagcttctg 1980 cagctcctaa aagttcagaa tgaagacgtt cagcgagctg tgtgtggggc cttgagaaac 2040 ttagtatttg aagacaatga caacaaattg gaggtggctg aactaaatgg ggtacctcgg 2100 ctgctccagg tgctgaagca aaccagagac ttggagacta aaaaacaaat aacaggtttg 2160 ctgtggaatt tgtcatctaa tgacaaactc aagaatctca tgataacaga agcattgctt 2220 acgctgacgg agaatatcat catccccttt tctgggtggc ctgaaggaga ctacccaaaa 2280 gcaaatggtt tgctcgattt tgacatattc tacaacgtca ctggatgcct aagaaacatg 2340 agttctgctg gcgctgatgg gagaaaagcg atgagaagat gtgacggact cattgactca 2400 ctggtccatt atgtcagagg aaccattgca gattaccagc cagatgacaa ggccacggag 2460 aattgtgtgt gcattcttca taacctctcc taccagctgg aggcagagct cccagagaaa 2520 tattcccaga atatctatat tcaaaaccgg aatatccaga ctgacaacaa caaaagtatt 2580 ggatgttttg gcagtcgaag caggaaagta aaagagcaat accaggacgt gccgatgccg 2640 gaggaaaaga gcaaccccaa gggcgtggag tggctgtggc attccattgt tataaggatg 2700 tatctgtcct tgatcgccaa aagtgtccgc aactacacac aagaagcatc cttaggagct 2760 ctgcagaacc tcacggccgg aagtggacca atgccgacat cagtggctca gacagttgtc 2820 cagaaggaaa gtggcctgca gcacacccga aagatgctgc atgttggtga cccaagtgtg 2880 aaaaagacag ccatctcgct gctgaggaat ctgtcccgga atctttctct gcagaatgaa 2940 attgccaaag aaactctccc tgatttggtt tccatcattc ctgacacagt cccgagtact 3000 gaccttctca ttgaaactac agcctctgcc tgttacacat tgaacaacat aatccaaaac 3060 agttaccaga atgcacgcga ccttctaaac accgggggca tccagaaaat tatggccatt 3120 agtgcaggcg atgcctatgc ctccaacaaa gcaagtaaag ctgcttccgt ccttctgtat 3180 tctctgtggg cacacacgga actgcatcat gcctacaaga aggctcagtt taagaagaca 3240 gattttgtca acagccggac tgccaaagcc taccactccc ttaaagactg atcaacctct 3300 ggattacaaa atttgtgaaa gattgactgg tattcttaac tatgttgctc cttttacgct 3360 atgtggatac gctgctttaa tgcctttgta tcatgctatt gcttcccgta tggctttcat 3420 tttctcctcc ttgtataaat cctggttgct gtctctttat gaggagttgt ggcccgttgt 3480 caggcaacgt ggcgtggtgt gcactgtgtt tgctgacgca acccccactg gttggggcat 3540 tgccaccacc tgtcagctcc tttccgggac tttcgctttc cccctcccta ttgccacggc 3600 ggaactcatc gccgcctgcc ttgcccgctg ctggacaggg gctcggctgt tgggcactga 3660 caattccgtg gtgttgtcgg ggaaatcatc gtcctttcct tggctgctcg cctgtgttgc 3720 cacctggatt ctgcgcggga cgtccttctg ctacgtccct tcggccctca atccagcgga 3780 ccttccttcc cgcggcctgc tgccggctct gcggcctctt ccgcgtcttc gccttcgccc 3840 tcagacgagt cggatctccc tttgggccgc ctccccgcac tgcccgggtg gcatccctgt 3900 gacccctccc cagtgcctct cctggccctg gaagttgcca ctccagtgcc caccagcctt 3960 gtcctaataa aattaagttg catcattttg tctgactagg tgtccttcta taatattatg 4020 gggtggaggg gggtggtatg gagcaagggg cccaagttgg gaagaaacct gtagggcctg 4080 c 4081 <210> SEQ ID NO 9 <211> LENGTH: 3854 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Made in lab - hTnT-PKP2a expression cassette <400> SEQUENCE: 9 ctcagtccat taggagccag tagcctggaa gatgtcttta cccccagcat cagttcaagt 60 ggagcagcac ataactcttg ccctctgcct tccaagattc tggtgctgag acttatggag 120 tgtcttggag gttgccttct gccccccaac cctgctccca gctggccctc ccaggcctgg 180 gttgctggcc tctgctttat caggattctc aagagggaca gctggtttat gttgcatgac 240 tgttccctgc atatctgctc tggttttaaa tagcttatct gagcagctgg aggaccacat 300 gggcttatat ggcgtggggt acatgttcct gtagccttgt ccctggcacc tgccaaaata 360 gcagccaaca ccccccaccc ccaccgccat ccccctgccc cacccgtccc ctgtcgcaca 420 ttcctccctc cgcagggctg gctcaccagg ccccagccca catgcctgct taaagccctc 480 tccatcctct gcctcaccca gtccccgctg agactgagca gacgcctcca ggatctgtcg 540 gcaggccacc atggcagccc ccggcgcccc agctgagtac ggctacatcc ggaccgtcct 600 gggccagcag atcctgggac aactggacag ctccagcctg gcgctgccct ccgaggccaa 660 gctgaagctg gcggggagca gcggccgcgg cggccagaca gtcaagagcc tgcggatcca 720 ggagcaggtg cagcagaccc tcgcccggaa gggccgcagc tccgtgggca acggaaatct 780 tcaccgaacc agcagtgttc ctgagtatgt ctacaaccta cacttggttg aaaatgattt 840 tgttggaggc cgttcccctg ttcctaaaac ctatgacatg ctaaaggctg gcacaactgc 900 cacttatgaa ggtcgctggg gaagaggaac agcacagtac agctcccaga agtccgtgga 960 agaaaggtcc ttgaggcatc ctctgaggag actggagatt tctcctgaca gcagcccgga 1020 gagggctcac tacacgcaca gcgattacca gtacagccag agaagccagg ctgggcacac 1080 cctgcaccac caagaaagca ggcgggccgc cctcctagtg ccaccgagat atgctcgttc 1140 cgagatcgtg ggggtcagcc gtgctggcac cacaagcagg cagcgccact ttgacacata 1200 ccacagacag taccagcatg gctctgttag cgacaccgtt tttgacagca tccctgccaa 1260 cccggccctg ctcacgtacc ccaggccagg gaccagccgc agcatgggca acctcttgga 1320 gaaggagaac tacctgacgg cagggctcac tgtcgggcag gtcaggccgc tggtgcccct 1380 gcagcccgtc actcagaaca gggcttccag gtcctcctgg catcagagct ccttccacag 1440 cacccgcacg ctgagggaag ctgggcccag tgtcgccgtg gattccagcg ggaggagagc 1500 gcacttgact gtcggccagg cggccgcagg gggaagtggg aatctgctca ctgagagaag 1560 cactttcact gactcccagc tggggaatgc agacatggag atgactctgg agcgagcagt 1620 gagtatgctc gaggcagacc acatgctgcc atccaggatt tctgctgcag ctactttcat 1680 acagcacgag tgcttccaga aatctgaagc tcggaagagg gttaaccagc ttcgtggcat 1740 cctcaagctt ctgcagctcc taaaagttca gaatgaagac gttcagcgag ctgtgtgtgg 1800 ggccttgaga aacttagtat ttgaagacaa tgacaacaaa ttggaggtgg ctgaactaaa 1860 tggggtacct cggctgctcc aggtgctgaa gcaaaccaga gacttggaga ctaaaaaaca 1920 aataacaggt ttgctgtgga atttgtcatc taatgacaaa ctcaagaatc tcatgataac 1980 agaagcattg cttacgctga cggagaatat catcatcccc ttttctgggt ggcctgaagg 2040 agactaccca aaagcaaatg gtttgctcga ttttgacata ttctacaacg tcactggatg 2100 cctaagaaac atgagttctg ctggcgctga tgggagaaaa gcgatgagaa gatgtgacgg 2160 actcattgac tcactggtcc attatgtcag aggaaccatt gcagattacc agccagatga 2220 caaggccacg gagaattgtg tgtgcattct tcataacctc tcctaccagc tggaggcaga 2280 gctcccagag aaatattccc agaatatcta tattcaaaac cggaatatcc agactgacaa 2340 caacaaaagt attggatgtt ttggcagtcg aagcaggaaa gtaaaagagc aataccagga 2400 cgtgccgatg ccggaggaaa agagcaaccc caagggcgtg gagtggctgt ggcattccat 2460 tgttataagg atgtatctgt ccttgatcgc caaaagtgtc cgcaactaca cacaagaagc 2520 atccttagga gctctgcaga acctcacggc cggaagtgga ccaatgccga catcagtggc 2580 tcagacagtt gtccagaagg aaagtggcct gcagcacacc cgaaagatgc tgcatgttgg 2640 tgacccaagt gtgaaaaaga cagccatctc gctgctgagg aatctgtccc ggaatctttc 2700 tctgcagaat gaaattgcca aagaaactct ccctgatttg gtttccatca ttcctgacac 2760 agtcccgagt actgaccttc tcattgaaac tacagcctct gcctgttaca cattgaacaa 2820 cataatccaa aacagttacc agaatgcacg cgaccttcta aacaccgggg gcatccagaa 2880

aattatggcc attagtgcag gcgatgccta tgcctccaac aaagcaagta aagctgcttc 2940 cgtccttctg tattctctgt gggcacacac ggaactgcat catgcctaca agaaggctca 3000 gtttaagaag acagattttg tcaacagccg gactgccaaa gcctaccact cccttaaaga 3060 ctgatcaacc tctggattac aaaatttgtg aaagattgac tggtattctt aactatgttg 3120 ctccttttac gctatgtgga tacgctgctt taatgccttt gtatcatgct attgcttccc 3180 gtatggcttt cattttctcc tccttgtata aatcctggtt gctgtctctt tatgaggagt 3240 tgtggcccgt tgtcaggcaa cgtggcgtgg tgtgcactgt gtttgctgac gcaaccccca 3300 ctggttgggg cattgccacc acctgtcagc tcctttccgg gactttcgct ttccccctcc 3360 ctattgccac ggcggaactc atcgccgcct gccttgcccg ctgctggaca ggggctcggc 3420 tgttgggcac tgacaattcc gtggtgttgt cggggaaatc atcgtccttt ccttggctgc 3480 tcgcctgtgt tgccacctgg attctgcgcg ggacgtcctt ctgctacgtc ccttcggccc 3540 tcaatccagc ggaccttcct tcccgcggcc tgctgccggc tctgcggcct cttccgcgtc 3600 ttcgccttcg ccctcagacg agtcggatct ccctttgggc cgcctccccg cactgcccgg 3660 gtggcatccc tgtgacccct ccccagtgcc tctcctggcc ctggaagttg ccactccagt 3720 gcccaccagc cttgtcctaa taaaattaag ttgcatcatt ttgtctgact aggtgtcctt 3780 ctataatatt atggggtgga ggggggtggt atggagcaag gggcccaagt tgggaagaaa 3840 cctgtagggc ctgc 3854 <210> SEQ ID NO 10 <211> LENGTH: 4213 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Made in Lab - MHCK7-PKP2b expression cassette <400> SEQUENCE: 10 acccttcaga ttaaaaataa ctgaggtaag ggcctgggta ggggaggtgg tgtgagacgc 60 tcctgtctct cctctatctg cccatcggcc ctttggggag gaggaatgtg cccaaggact 120 aaaaaaaggc catggagcca gaggggcgag ggcaacagac ctttcatggg caaaccttgg 180 ggccctgctg tctagcatgc cccactacgg gtctaggctg cccatgtaag gaggcaaggc 240 ctggggacac ccgagatgcc tggttataat taacccagac atgtggctgc cccccccccc 300 ccaacacctg ctgcctctaa aaataaccct gtccctggtg gatcccctgc atgcgaagat 360 cttcgaacaa ggctgtgggg gactgagggc aggctgtaac aggcttgggg gccagggctt 420 atacgtgcct gggactccca aagtattact gttccatgtt cccggcgaag ggccagctgt 480 cccccgccag ctagactcag cacttagttt aggaaccagt gagcaagtca gcccttgggg 540 cagcccatac aaggccatgg ggctgggcaa gctgcacgcc tgggtccggg gtgggcacgg 600 tgcccgggca acgagctgaa agctcatctg ctctcagggg cccctccctg gggacagccc 660 ctcctggcta gtcacaccct gtaggctcct ctatataacc caggggcaca ggggctgccc 720 tcattctacc accacctcca cagcacagac agacactcag gagccagcca ggccaccatg 780 gcagcccccg gcgccccagc tgagtacggc tacatccgga ccgtcctggg ccagcagatc 840 ctgggacaac tggacagctc cagcctggcg ctgccctccg aggccaagct gaagctggcg 900 gggagcagcg gccgcggcgg ccagacagtc aagagcctgc ggatccagga gcaggtgcag 960 cagaccctcg cccggaaggg ccgcagctcc gtgggcaacg gaaatcttca ccgaaccagc 1020 agtgttcctg agtatgtcta caacctacac ttggttgaaa atgattttgt tggaggccgt 1080 tcccctgttc ctaaaaccta tgacatgcta aaggctggca caactgccac ttatgaaggt 1140 cgctggggaa gaggaacagc acagtacagc tcccagaagt ccgtggaaga aaggtccttg 1200 aggcatcctc tgaggagact ggagatttct cctgacagca gcccggagag ggctcactac 1260 acgcacagcg attaccagta cagccagaga agccaggctg ggcacaccct gcaccaccaa 1320 gaaagcaggc gggccgccct cctagtgcca ccgagatatg ctcgttccga gatcgtgggg 1380 gtcagccgtg ctggcaccac aagcaggcag cgccactttg acacatacca cagacagtac 1440 cagcatggct ctgttagcga caccgttttt gacagcatcc ctgccaaccc ggccctgctc 1500 acgtacccca ggccagggac cagccgcagc atgggcaacc tcttggagaa ggagaactac 1560 ctgacggcag ggctcactgt cgggcaggtc aggccgctgg tgcccctgca gcccgtcact 1620 cagaacaggg cttccaggtc ctcctggcat cagagctcct tccacagcac ccgcacgctg 1680 agggaagctg ggcccagtgt cgccgtggat tccagcggga ggagagcgca cttgactgtc 1740 ggccaggcgg ccgcaggggg aagtgggaat ctgctcactg agagaagcac tttcactgac 1800 tcccagctgg ggaatgcaga catggagatg actctggagc gagcagtgag tatgctcgag 1860 gcagaccaca tgctgccatc caggatttct gctgcagcta ctttcataca gcacgagtgc 1920 ttccagaaat ctgaagctcg gaagagggtt aaccagcttc gtggcatcct caagcttctg 1980 cagctcctaa aagttcagaa tgaagacgtt cagcgagctg tgtgtggggc cttgagaaac 2040 ttagtatttg aagacaatga caacaaattg gaggtggctg aactaaatgg ggtacctcgg 2100 ctgctccagg tgctgaagca aaccagagac ttggagacta aaaaacaaat aacagaccat 2160 acagtcaatt taagaagtag gaatggctgg ccgggcgcgg tggctcacgc ctgtaatccc 2220 agcactttgg gaggccaagg cgggcggatc acgaggtcag gagttcgaga ccagcctgac 2280 caacatggtt tgctgtggaa tttgtcatct aatgacaaac tcaagaatct catgataaca 2340 gaagcattgc ttacgctgac ggagaatatc atcatcccct tttctgggtg gcctgaagga 2400 gactacccaa aagcaaatgg tttgctcgat tttgacatat tctacaacgt cactggatgc 2460 ctaagaaaca tgagttctgc tggcgctgat gggagaaaag cgatgagaag atgtgacgga 2520 ctcattgact cactggtcca ttatgtcaga ggaaccattg cagattacca gccagatgac 2580 aaggccacgg agaattgtgt gtgcattctt cataacctct cctaccagct ggaggcagag 2640 ctcccagaga aatattccca gaatatctat attcaaaacc ggaatatcca gactgacaac 2700 aacaaaagta ttggatgttt tggcagtcga agcaggaaag taaaagagca ataccaggac 2760 gtgccgatgc cggaggaaaa gagcaacccc aagggcgtgg agtggctgtg gcattccatt 2820 gttataagga tgtatctgtc cttgatcgcc aaaagtgtcc gcaactacac acaagaagca 2880 tccttaggag ctctgcagaa cctcacggcc ggaagtggac caatgccgac atcagtggct 2940 cagacagttg tccagaagga aagtggcctg cagcacaccc gaaagatgct gcatgttggt 3000 gacccaagtg tgaaaaagac agccatctcg ctgctgagga atctgtcccg gaatctttct 3060 ctgcagaatg aaattgccaa agaaactctc cctgatttgg tttccatcat tcctgacaca 3120 gtcccgagta ctgaccttct cattgaaact acagcctctg cctgttacac attgaacaac 3180 ataatccaaa acagttacca gaatgcacgc gaccttctaa acaccggggg catccagaaa 3240 attatggcca ttagtgcagg cgatgcctat gcctccaaca aagcaagtaa agctgcttcc 3300 gtccttctgt attctctgtg ggcacacacg gaactgcatc atgcctacaa gaaggctcag 3360 tttaagaaga cagattttgt caacagccgg actgccaaag cctaccactc ccttaaagac 3420 tgatcaacct ctggattaca aaatttgtga aagattgact ggtattctta actatgttgc 3480 tccttttacg ctatgtggat acgctgcttt aatgcctttg tatcatgcta ttgcttcccg 3540 tatggctttc attttctcct ccttgtataa atcctggttg ctgtctcttt atgaggagtt 3600 gtggcccgtt gtcaggcaac gtggcgtggt gtgcactgtg tttgctgacg caacccccac 3660 tggttggggc attgccacca cctgtcagct cctttccggg actttcgctt tccccctccc 3720 tattgccacg gcggaactca tcgccgcctg ccttgcccgc tgctggacag gggctcggct 3780 gttgggcact gacaattccg tggtgttgtc ggggaaatca tcgtcctttc cttggctgct 3840 cgcctgtgtt gccacctgga ttctgcgcgg gacgtccttc tgctacgtcc cttcggccct 3900 caatccagcg gaccttcctt cccgcggcct gctgccggct ctgcggcctc ttccgcgtct 3960 tcgccttcgc cctcagacga gtcggatctc cctttgggcc gcctccccgc actgcccggg 4020 tggcatccct gtgacccctc cccagtgcct ctcctggccc tggaagttgc cactccagtg 4080 cccaccagcc ttgtcctaat aaaattaagt tgcatcattt tgtctgacta ggtgtccttc 4140 tataatatta tggggtggag gggggtggta tggagcaagg ggcccaagtt gggaagaaac 4200 ctgtagggcc tgc 4213 <210> SEQ ID NO 11 <211> LENGTH: 3986 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Made in Lab - hTnT-PKP2b express cassette <400> SEQUENCE: 11 ctcagtccat taggagccag tagcctggaa gatgtcttta cccccagcat cagttcaagt 60 ggagcagcac ataactcttg ccctctgcct tccaagattc tggtgctgag acttatggag 120 tgtcttggag gttgccttct gccccccaac cctgctccca gctggccctc ccaggcctgg 180 gttgctggcc tctgctttat caggattctc aagagggaca gctggtttat gttgcatgac 240 tgttccctgc atatctgctc tggttttaaa tagcttatct gagcagctgg aggaccacat 300 gggcttatat ggcgtggggt acatgttcct gtagccttgt ccctggcacc tgccaaaata 360 gcagccaaca ccccccaccc ccaccgccat ccccctgccc cacccgtccc ctgtcgcaca 420 ttcctccctc cgcagggctg gctcaccagg ccccagccca catgcctgct taaagccctc 480 tccatcctct gcctcaccca gtccccgctg agactgagca gacgcctcca ggatctgtcg 540 gcaggccacc atggcagccc ccggcgcccc agctgagtac ggctacatcc ggaccgtcct 600 gggccagcag atcctgggac aactggacag ctccagcctg gcgctgccct ccgaggccaa 660 gctgaagctg gcggggagca gcggccgcgg cggccagaca gtcaagagcc tgcggatcca 720 ggagcaggtg cagcagaccc tcgcccggaa gggccgcagc tccgtgggca acggaaatct 780 tcaccgaacc agcagtgttc ctgagtatgt ctacaaccta cacttggttg aaaatgattt 840 tgttggaggc cgttcccctg ttcctaaaac ctatgacatg ctaaaggctg gcacaactgc 900 cacttatgaa ggtcgctggg gaagaggaac agcacagtac agctcccaga agtccgtgga 960 agaaaggtcc ttgaggcatc ctctgaggag actggagatt tctcctgaca gcagcccgga 1020 gagggctcac tacacgcaca gcgattacca gtacagccag agaagccagg ctgggcacac 1080 cctgcaccac caagaaagca ggcgggccgc cctcctagtg ccaccgagat atgctcgttc 1140 cgagatcgtg ggggtcagcc gtgctggcac cacaagcagg cagcgccact ttgacacata 1200 ccacagacag taccagcatg gctctgttag cgacaccgtt tttgacagca tccctgccaa 1260 cccggccctg ctcacgtacc ccaggccagg gaccagccgc agcatgggca acctcttgga 1320 gaaggagaac tacctgacgg cagggctcac tgtcgggcag gtcaggccgc tggtgcccct 1380 gcagcccgtc actcagaaca gggcttccag gtcctcctgg catcagagct ccttccacag 1440 cacccgcacg ctgagggaag ctgggcccag tgtcgccgtg gattccagcg ggaggagagc 1500 gcacttgact gtcggccagg cggccgcagg gggaagtggg aatctgctca ctgagagaag 1560 cactttcact gactcccagc tggggaatgc agacatggag atgactctgg agcgagcagt 1620

gagtatgctc gaggcagacc acatgctgcc atccaggatt tctgctgcag ctactttcat 1680 acagcacgag tgcttccaga aatctgaagc tcggaagagg gttaaccagc ttcgtggcat 1740 cctcaagctt ctgcagctcc taaaagttca gaatgaagac gttcagcgag ctgtgtgtgg 1800 ggccttgaga aacttagtat ttgaagacaa tgacaacaaa ttggaggtgg ctgaactaaa 1860 tggggtacct cggctgctcc aggtgctgaa gcaaaccaga gacttggaga ctaaaaaaca 1920 aataacagac catacagtca atttaagaag taggaatggc tggccgggcg cggtggctca 1980 cgcctgtaat cccagcactt tgggaggcca aggcgggcgg atcacgaggt caggagttcg 2040 agaccagcct gaccaacatg gtttgctgtg gaatttgtca tctaatgaca aactcaagaa 2100 tctcatgata acagaagcat tgcttacgct gacggagaat atcatcatcc ccttttctgg 2160 gtggcctgaa ggagactacc caaaagcaaa tggtttgctc gattttgaca tattctacaa 2220 cgtcactgga tgcctaagaa acatgagttc tgctggcgct gatgggagaa aagcgatgag 2280 aagatgtgac ggactcattg actcactggt ccattatgtc agaggaacca ttgcagatta 2340 ccagccagat gacaaggcca cggagaattg tgtgtgcatt cttcataacc tctcctacca 2400 gctggaggca gagctcccag agaaatattc ccagaatatc tatattcaaa accggaatat 2460 ccagactgac aacaacaaaa gtattggatg ttttggcagt cgaagcagga aagtaaaaga 2520 gcaataccag gacgtgccga tgccggagga aaagagcaac cccaagggcg tggagtggct 2580 gtggcattcc attgttataa ggatgtatct gtccttgatc gccaaaagtg tccgcaacta 2640 cacacaagaa gcatccttag gagctctgca gaacctcacg gccggaagtg gaccaatgcc 2700 gacatcagtg gctcagacag ttgtccagaa ggaaagtggc ctgcagcaca cccgaaagat 2760 gctgcatgtt ggtgacccaa gtgtgaaaaa gacagccatc tcgctgctga ggaatctgtc 2820 ccggaatctt tctctgcaga atgaaattgc caaagaaact ctccctgatt tggtttccat 2880 cattcctgac acagtcccga gtactgacct tctcattgaa actacagcct ctgcctgtta 2940 cacattgaac aacataatcc aaaacagtta ccagaatgca cgcgaccttc taaacaccgg 3000 gggcatccag aaaattatgg ccattagtgc aggcgatgcc tatgcctcca acaaagcaag 3060 taaagctgct tccgtccttc tgtattctct gtgggcacac acggaactgc atcatgccta 3120 caagaaggct cagtttaaga agacagattt tgtcaacagc cggactgcca aagcctacca 3180 ctcccttaaa gactgatcaa cctctggatt acaaaatttg tgaaagattg actggtattc 3240 ttaactatgt tgctcctttt acgctatgtg gatacgctgc tttaatgcct ttgtatcatg 3300 ctattgcttc ccgtatggct ttcattttct cctccttgta taaatcctgg ttgctgtctc 3360 tttatgagga gttgtggccc gttgtcaggc aacgtggcgt ggtgtgcact gtgtttgctg 3420 acgcaacccc cactggttgg ggcattgcca ccacctgtca gctcctttcc gggactttcg 3480 ctttccccct ccctattgcc acggcggaac tcatcgccgc ctgccttgcc cgctgctgga 3540 caggggctcg gctgttgggc actgacaatt ccgtggtgtt gtcggggaaa tcatcgtcct 3600 ttccttggct gctcgcctgt gttgccacct ggattctgcg cgggacgtcc ttctgctacg 3660 tcccttcggc cctcaatcca gcggaccttc cttcccgcgg cctgctgccg gctctgcggc 3720 ctcttccgcg tcttcgcctt cgccctcaga cgagtcggat ctccctttgg gccgcctccc 3780 cgcactgccc gggtggcatc cctgtgaccc ctccccagtg cctctcctgg ccctggaagt 3840 tgccactcca gtgcccacca gccttgtcct aataaaatta agttgcatca ttttgtctga 3900 ctaggtgtcc ttctataata ttatggggtg gaggggggtg gtatggagca aggggcccaa 3960 gttgggaaga aacctgtagg gcctgc 3986 <210> SEQ ID NO 12 <211> LENGTH: 4417 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Made in Labe - full polynucleotide sequence of vector genome <400> SEQUENCE: 12 gcgcgctcgc tcgctcactg aggccgcccg ggcaaagccc gggcgtcggg cgacctttgg 60 tcgcccggcc tcagtgagcg agcgagcgcg cagagaggga gtggccaact ccatcactag 120 gggttccttg tagttaatga ttaacccgcc atgctactta tctacgtaac ccttcagatt 180 aaaaataact gaggtaaggg cctgggtagg ggaggtggtg tgagacgctc ctgtctctcc 240 tctatctgcc catcggccct ttggggagga ggaatgtgcc caaggactaa aaaaaggcca 300 tggagccaga ggggcgaggg caacagacct ttcatgggca aaccttgggg ccctgctgtc 360 tagcatgccc cactacgggt ctaggctgcc catgtaagga ggcaaggcct ggggacaccc 420 gagatgcctg gttataatta acccagacat gtggctgccc cccccccccc aacacctgct 480 gcctctaaaa ataaccctgt ccctggtgga tcccctgcat gcgaagatct tcgaacaagg 540 ctgtggggga ctgagggcag gctgtaacag gcttgggggc cagggcttat acgtgcctgg 600 gactcccaaa gtattactgt tccatgttcc cggcgaaggg ccagctgtcc cccgccagct 660 agactcagca cttagtttag gaaccagtga gcaagtcagc ccttggggca gcccatacaa 720 ggccatgggg ctgggcaagc tgcacgcctg ggtccggggt gggcacggtg cccgggcaac 780 gagctgaaag ctcatctgct ctcaggggcc cctccctggg gacagcccct cctggctagt 840 cacaccctgt aggctcctct atataaccca ggggcacagg ggctgccctc attctaccac 900 cacctccaca gcacagacag acactcagga gccagccagg ccaccatggc agcccccggc 960 gccccagctg agtacggcta catccggacc gtcctgggcc agcagatcct gggacaactg 1020 gacagctcca gcctggcgct gccctccgag gccaagctga agctggcggg gagcagcggc 1080 cgcggcggcc agacagtcaa gagcctgcgg atccaggagc aggtgcagca gaccctcgcc 1140 cggaagggcc gcagctccgt gggcaacgga aatcttcacc gaaccagcag tgttcctgag 1200 tatgtctaca acctacactt ggttgaaaat gattttgttg gaggccgttc ccctgttcct 1260 aaaacctatg acatgctaaa ggctggcaca actgccactt atgaaggtcg ctggggaaga 1320 ggaacagcac agtacagctc ccagaagtcc gtggaagaaa ggtccttgag gcatcctctg 1380 aggagactgg agatttctcc tgacagcagc ccggagaggg ctcactacac gcacagcgat 1440 taccagtaca gccagagaag ccaggctggg cacaccctgc accaccaaga aagcaggcgg 1500 gccgccctcc tagtgccacc gagatatgct cgttccgaga tcgtgggggt cagccgtgct 1560 ggcaccacaa gcaggcagcg ccactttgac acataccaca gacagtacca gcatggctct 1620 gttagcgaca ccgtttttga cagcatccct gccaacccgg ccctgctcac gtaccccagg 1680 ccagggacca gccgcagcat gggcaacctc ttggagaagg agaactacct gacggcaggg 1740 ctcactgtcg ggcaggtcag gccgctggtg cccctgcagc ccgtcactca gaacagggct 1800 tccaggtcct cctggcatca gagctccttc cacagcaccc gcacgctgag ggaagctggg 1860 cccagtgtcg ccgtggattc cagcgggagg agagcgcact tgactgtcgg ccaggcggcc 1920 gcagggggaa gtgggaatct gctcactgag agaagcactt tcactgactc ccagctgggg 1980 aatgcagaca tggagatgac tctggagcga gcagtgagta tgctcgaggc agaccacatg 2040 ctgccatcca ggatttctgc tgcagctact ttcatacagc acgagtgctt ccagaaatct 2100 gaagctcgga agagggttaa ccagcttcgt ggcatcctca agcttctgca gctcctaaaa 2160 gttcagaatg aagacgttca gcgagctgtg tgtggggcct tgagaaactt agtatttgaa 2220 gacaatgaca acaaattgga ggtggctgaa ctaaatgggg tacctcggct gctccaggtg 2280 ctgaagcaaa ccagagactt ggagactaaa aaacaaataa caggtttgct gtggaatttg 2340 tcatctaatg acaaactcaa gaatctcatg ataacagaag cattgcttac gctgacggag 2400 aatatcatca tccccttttc tgggtggcct gaaggagact acccaaaagc aaatggtttg 2460 ctcgattttg acatattcta caacgtcact ggatgcctaa gaaacatgag ttctgctggc 2520 gctgatggga gaaaagcgat gagaagatgt gacggactca ttgactcact ggtccattat 2580 gtcagaggaa ccattgcaga ttaccagcca gatgacaagg ccacggagaa ttgtgtgtgc 2640 attcttcata acctctccta ccagctggag gcagagctcc cagagaaata ttcccagaat 2700 atctatattc aaaaccggaa tatccagact gacaacaaca aaagtattgg atgttttggc 2760 agtcgaagca ggaaagtaaa agagcaatac caggacgtgc cgatgccgga ggaaaagagc 2820 aaccccaagg gcgtggagtg gctgtggcat tccattgtta taaggatgta tctgtccttg 2880 atcgccaaaa gtgtccgcaa ctacacacaa gaagcatcct taggagctct gcagaacctc 2940 acggccggaa gtggaccaat gccgacatca gtggctcaga cagttgtcca gaaggaaagt 3000 ggcctgcagc acacccgaaa gatgctgcat gttggtgacc caagtgtgaa aaagacagcc 3060 atctcgctgc tgaggaatct gtcccggaat ctttctctgc agaatgaaat tgccaaagaa 3120 actctccctg atttggtttc catcattcct gacacagtcc cgagtactga ccttctcatt 3180 gaaactacag cctctgcctg ttacacattg aacaacataa tccaaaacag ttaccagaat 3240 gcacgcgacc ttctaaacac cgggggcatc cagaaaatta tggccattag tgcaggcgat 3300 gcctatgcct ccaacaaagc aagtaaagct gcttccgtcc ttctgtattc tctgtgggca 3360 cacacggaac tgcatcatgc ctacaagaag gctcagttta agaagacaga ttttgtcaac 3420 agccggactg ccaaagccta ccactccctt aaagactgat caacctctgg attacaaaat 3480 ttgtgaaaga ttgactggta ttcttaacta tgttgctcct tttacgctat gtggatacgc 3540 tgctttaatg cctttgtatc atgctattgc ttcccgtatg gctttcattt tctcctcctt 3600 gtataaatcc tggttgctgt ctctttatga ggagttgtgg cccgttgtca ggcaacgtgg 3660 cgtggtgtgc actgtgtttg ctgacgcaac ccccactggt tggggcattg ccaccacctg 3720 tcagctcctt tccgggactt tcgctttccc cctccctatt gccacggcgg aactcatcgc 3780 cgcctgcctt gcccgctgct ggacaggggc tcggctgttg ggcactgaca attccgtggt 3840 gttgtcgggg aaatcatcgt cctttccttg gctgctcgcc tgtgttgcca cctggattct 3900 gcgcgggacg tccttctgct acgtcccttc ggccctcaat ccagcggacc ttccttcccg 3960 cggcctgctg ccggctctgc ggcctcttcc gcgtcttcgc cttcgccctc agacgagtcg 4020 gatctccctt tgggccgcct ccccgcactg cccgggtggc atccctgtga cccctcccca 4080 gtgcctctcc tggccctgga agttgccact ccagtgccca ccagccttgt cctaataaaa 4140 ttaagttgca tcattttgtc tgactaggtg tccttctata atattatggg gtggaggggg 4200 gtggtatgga gcaaggggcc caagttggga agaaacctgt agggcctgct acgtagataa 4260 gtagcatggc gggttaatca ttaactacaa ggaaccccta gtgatggagt tggccactcc 4320 ctctctgcgc gctcgctcgc tcactgaggc cgggcgacca aaggtcgccc gacgcccggg 4380 ctttgcccgg gcggcctcag tgagcgagcg agcgcgc 4417 <210> SEQ ID NO 13 <211> LENGTH: 4190 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Made in Labe - full polynucleotide sequence of vector genome <400> SEQUENCE: 13

gcgcgctcgc tcgctcactg aggccgcccg ggcaaagccc gggcgtcggg cgacctttgg 60 tcgcccggcc tcagtgagcg agcgagcgcg cagagaggga gtggccaact ccatcactag 120 gggttccttg tagttaatga ttaacccgcc atgctactta tctacgtact cagtccatta 180 ggagccagta gcctggaaga tgtctttacc cccagcatca gttcaagtgg agcagcacat 240 aactcttgcc ctctgccttc caagattctg gtgctgagac ttatggagtg tcttggaggt 300 tgccttctgc cccccaaccc tgctcccagc tggccctccc aggcctgggt tgctggcctc 360 tgctttatca ggattctcaa gagggacagc tggtttatgt tgcatgactg ttccctgcat 420 atctgctctg gttttaaata gcttatctga gcagctggag gaccacatgg gcttatatgg 480 cgtggggtac atgttcctgt agccttgtcc ctggcacctg ccaaaatagc agccaacacc 540 ccccaccccc accgccatcc ccctgcccca cccgtcccct gtcgcacatt cctccctccg 600 cagggctggc tcaccaggcc ccagcccaca tgcctgctta aagccctctc catcctctgc 660 ctcacccagt ccccgctgag actgagcaga cgcctccagg atctgtcggc aggccaccat 720 ggcagccccc ggcgccccag ctgagtacgg ctacatccgg accgtcctgg gccagcagat 780 cctgggacaa ctggacagct ccagcctggc gctgccctcc gaggccaagc tgaagctggc 840 ggggagcagc ggccgcggcg gccagacagt caagagcctg cggatccagg agcaggtgca 900 gcagaccctc gcccggaagg gccgcagctc cgtgggcaac ggaaatcttc accgaaccag 960 cagtgttcct gagtatgtct acaacctaca cttggttgaa aatgattttg ttggaggccg 1020 ttcccctgtt cctaaaacct atgacatgct aaaggctggc acaactgcca cttatgaagg 1080 tcgctgggga agaggaacag cacagtacag ctcccagaag tccgtggaag aaaggtcctt 1140 gaggcatcct ctgaggagac tggagatttc tcctgacagc agcccggaga gggctcacta 1200 cacgcacagc gattaccagt acagccagag aagccaggct gggcacaccc tgcaccacca 1260 agaaagcagg cgggccgccc tcctagtgcc accgagatat gctcgttccg agatcgtggg 1320 ggtcagccgt gctggcacca caagcaggca gcgccacttt gacacatacc acagacagta 1380 ccagcatggc tctgttagcg acaccgtttt tgacagcatc cctgccaacc cggccctgct 1440 cacgtacccc aggccaggga ccagccgcag catgggcaac ctcttggaga aggagaacta 1500 cctgacggca gggctcactg tcgggcaggt caggccgctg gtgcccctgc agcccgtcac 1560 tcagaacagg gcttccaggt cctcctggca tcagagctcc ttccacagca cccgcacgct 1620 gagggaagct gggcccagtg tcgccgtgga ttccagcggg aggagagcgc acttgactgt 1680 cggccaggcg gccgcagggg gaagtgggaa tctgctcact gagagaagca ctttcactga 1740 ctcccagctg gggaatgcag acatggagat gactctggag cgagcagtga gtatgctcga 1800 ggcagaccac atgctgccat ccaggatttc tgctgcagct actttcatac agcacgagtg 1860 cttccagaaa tctgaagctc ggaagagggt taaccagctt cgtggcatcc tcaagcttct 1920 gcagctccta aaagttcaga atgaagacgt tcagcgagct gtgtgtgggg ccttgagaaa 1980 cttagtattt gaagacaatg acaacaaatt ggaggtggct gaactaaatg gggtacctcg 2040 gctgctccag gtgctgaagc aaaccagaga cttggagact aaaaaacaaa taacaggttt 2100 gctgtggaat ttgtcatcta atgacaaact caagaatctc atgataacag aagcattgct 2160 tacgctgacg gagaatatca tcatcccctt ttctgggtgg cctgaaggag actacccaaa 2220 agcaaatggt ttgctcgatt ttgacatatt ctacaacgtc actggatgcc taagaaacat 2280 gagttctgct ggcgctgatg ggagaaaagc gatgagaaga tgtgacggac tcattgactc 2340 actggtccat tatgtcagag gaaccattgc agattaccag ccagatgaca aggccacgga 2400 gaattgtgtg tgcattcttc ataacctctc ctaccagctg gaggcagagc tcccagagaa 2460 atattcccag aatatctata ttcaaaaccg gaatatccag actgacaaca acaaaagtat 2520 tggatgtttt ggcagtcgaa gcaggaaagt aaaagagcaa taccaggacg tgccgatgcc 2580 ggaggaaaag agcaacccca agggcgtgga gtggctgtgg cattccattg ttataaggat 2640 gtatctgtcc ttgatcgcca aaagtgtccg caactacaca caagaagcat ccttaggagc 2700 tctgcagaac ctcacggccg gaagtggacc aatgccgaca tcagtggctc agacagttgt 2760 ccagaaggaa agtggcctgc agcacacccg aaagatgctg catgttggtg acccaagtgt 2820 gaaaaagaca gccatctcgc tgctgaggaa tctgtcccgg aatctttctc tgcagaatga 2880 aattgccaaa gaaactctcc ctgatttggt ttccatcatt cctgacacag tcccgagtac 2940 tgaccttctc attgaaacta cagcctctgc ctgttacaca ttgaacaaca taatccaaaa 3000 cagttaccag aatgcacgcg accttctaaa caccgggggc atccagaaaa ttatggccat 3060 tagtgcaggc gatgcctatg cctccaacaa agcaagtaaa gctgcttccg tccttctgta 3120 ttctctgtgg gcacacacgg aactgcatca tgcctacaag aaggctcagt ttaagaagac 3180 agattttgtc aacagccgga ctgccaaagc ctaccactcc cttaaagact gatcaacctc 3240 tggattacaa aatttgtgaa agattgactg gtattcttaa ctatgttgct ccttttacgc 3300 tatgtggata cgctgcttta atgcctttgt atcatgctat tgcttcccgt atggctttca 3360 ttttctcctc cttgtataaa tcctggttgc tgtctcttta tgaggagttg tggcccgttg 3420 tcaggcaacg tggcgtggtg tgcactgtgt ttgctgacgc aacccccact ggttggggca 3480 ttgccaccac ctgtcagctc ctttccggga ctttcgcttt ccccctccct attgccacgg 3540 cggaactcat cgccgcctgc cttgcccgct gctggacagg ggctcggctg ttgggcactg 3600 acaattccgt ggtgttgtcg gggaaatcat cgtcctttcc ttggctgctc gcctgtgttg 3660 ccacctggat tctgcgcggg acgtccttct gctacgtccc ttcggccctc aatccagcgg 3720 accttccttc ccgcggcctg ctgccggctc tgcggcctct tccgcgtctt cgccttcgcc 3780 ctcagacgag tcggatctcc ctttgggccg cctccccgca ctgcccgggt ggcatccctg 3840 tgacccctcc ccagtgcctc tcctggccct ggaagttgcc actccagtgc ccaccagcct 3900 tgtcctaata aaattaagtt gcatcatttt gtctgactag gtgtccttct ataatattat 3960 ggggtggagg ggggtggtat ggagcaaggg gcccaagttg ggaagaaacc tgtagggcct 4020 gctacgtaga taagtagcat ggcgggttaa tcattaacta caaggaaccc ctagtgatgg 4080 agttggccac tccctctctg cgcgctcgct cgctcactga ggccgggcga ccaaaggtcg 4140 cccgacgccc gggctttgcc cgggcggcct cagtgagcga gcgagcgcgc 4190 <210> SEQ ID NO 14 <211> LENGTH: 4549 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Made in Labe - full polynucleotide sequence of vector genome <400> SEQUENCE: 14 gcgcgctcgc tcgctcactg aggccgcccg ggcaaagccc gggcgtcggg cgacctttgg 60 tcgcccggcc tcagtgagcg agcgagcgcg cagagaggga gtggccaact ccatcactag 120 gggttccttg tagttaatga ttaacccgcc atgctactta tctacgtaac ccttcagatt 180 aaaaataact gaggtaaggg cctgggtagg ggaggtggtg tgagacgctc ctgtctctcc 240 tctatctgcc catcggccct ttggggagga ggaatgtgcc caaggactaa aaaaaggcca 300 tggagccaga ggggcgaggg caacagacct ttcatgggca aaccttgggg ccctgctgtc 360 tagcatgccc cactacgggt ctaggctgcc catgtaagga ggcaaggcct ggggacaccc 420 gagatgcctg gttataatta acccagacat gtggctgccc cccccccccc aacacctgct 480 gcctctaaaa ataaccctgt ccctggtgga tcccctgcat gcgaagatct tcgaacaagg 540 ctgtggggga ctgagggcag gctgtaacag gcttgggggc cagggcttat acgtgcctgg 600 gactcccaaa gtattactgt tccatgttcc cggcgaaggg ccagctgtcc cccgccagct 660 agactcagca cttagtttag gaaccagtga gcaagtcagc ccttggggca gcccatacaa 720 ggccatgggg ctgggcaagc tgcacgcctg ggtccggggt gggcacggtg cccgggcaac 780 gagctgaaag ctcatctgct ctcaggggcc cctccctggg gacagcccct cctggctagt 840 cacaccctgt aggctcctct atataaccca ggggcacagg ggctgccctc attctaccac 900 cacctccaca gcacagacag acactcagga gccagccagg ccaccatggc agcccccggc 960 gccccagctg agtacggcta catccggacc gtcctgggcc agcagatcct gggacaactg 1020 gacagctcca gcctggcgct gccctccgag gccaagctga agctggcggg gagcagcggc 1080 cgcggcggcc agacagtcaa gagcctgcgg atccaggagc aggtgcagca gaccctcgcc 1140 cggaagggcc gcagctccgt gggcaacgga aatcttcacc gaaccagcag tgttcctgag 1200 tatgtctaca acctacactt ggttgaaaat gattttgttg gaggccgttc ccctgttcct 1260 aaaacctatg acatgctaaa ggctggcaca actgccactt atgaaggtcg ctggggaaga 1320 ggaacagcac agtacagctc ccagaagtcc gtggaagaaa ggtccttgag gcatcctctg 1380 aggagactgg agatttctcc tgacagcagc ccggagaggg ctcactacac gcacagcgat 1440 taccagtaca gccagagaag ccaggctggg cacaccctgc accaccaaga aagcaggcgg 1500 gccgccctcc tagtgccacc gagatatgct cgttccgaga tcgtgggggt cagccgtgct 1560 ggcaccacaa gcaggcagcg ccactttgac acataccaca gacagtacca gcatggctct 1620 gttagcgaca ccgtttttga cagcatccct gccaacccgg ccctgctcac gtaccccagg 1680 ccagggacca gccgcagcat gggcaacctc ttggagaagg agaactacct gacggcaggg 1740 ctcactgtcg ggcaggtcag gccgctggtg cccctgcagc ccgtcactca gaacagggct 1800 tccaggtcct cctggcatca gagctccttc cacagcaccc gcacgctgag ggaagctggg 1860 cccagtgtcg ccgtggattc cagcgggagg agagcgcact tgactgtcgg ccaggcggcc 1920 gcagggggaa gtgggaatct gctcactgag agaagcactt tcactgactc ccagctgggg 1980 aatgcagaca tggagatgac tctggagcga gcagtgagta tgctcgaggc agaccacatg 2040 ctgccatcca ggatttctgc tgcagctact ttcatacagc acgagtgctt ccagaaatct 2100 gaagctcgga agagggttaa ccagcttcgt ggcatcctca agcttctgca gctcctaaaa 2160 gttcagaatg aagacgttca gcgagctgtg tgtggggcct tgagaaactt agtatttgaa 2220 gacaatgaca acaaattgga ggtggctgaa ctaaatgggg tacctcggct gctccaggtg 2280 ctgaagcaaa ccagagactt ggagactaaa aaacaaataa cagaccatac agtcaattta 2340 agaagtagga atggctggcc gggcgcggtg gctcacgcct gtaatcccag cactttggga 2400 ggccaaggcg ggcggatcac gaggtcagga gttcgagacc agcctgacca acatggtttg 2460 ctgtggaatt tgtcatctaa tgacaaactc aagaatctca tgataacaga agcattgctt 2520 acgctgacgg agaatatcat catccccttt tctgggtggc ctgaaggaga ctacccaaaa 2580 gcaaatggtt tgctcgattt tgacatattc tacaacgtca ctggatgcct aagaaacatg 2640 agttctgctg gcgctgatgg gagaaaagcg atgagaagat gtgacggact cattgactca 2700 ctggtccatt atgtcagagg aaccattgca gattaccagc cagatgacaa ggccacggag 2760 aattgtgtgt gcattcttca taacctctcc taccagctgg aggcagagct cccagagaaa 2820 tattcccaga atatctatat tcaaaaccgg aatatccaga ctgacaacaa caaaagtatt 2880 ggatgttttg gcagtcgaag caggaaagta aaagagcaat accaggacgt gccgatgccg 2940

gaggaaaaga gcaaccccaa gggcgtggag tggctgtggc attccattgt tataaggatg 3000 tatctgtcct tgatcgccaa aagtgtccgc aactacacac aagaagcatc cttaggagct 3060 ctgcagaacc tcacggccgg aagtggacca atgccgacat cagtggctca gacagttgtc 3120 cagaaggaaa gtggcctgca gcacacccga aagatgctgc atgttggtga cccaagtgtg 3180 aaaaagacag ccatctcgct gctgaggaat ctgtcccgga atctttctct gcagaatgaa 3240 attgccaaag aaactctccc tgatttggtt tccatcattc ctgacacagt cccgagtact 3300 gaccttctca ttgaaactac agcctctgcc tgttacacat tgaacaacat aatccaaaac 3360 agttaccaga atgcacgcga ccttctaaac accgggggca tccagaaaat tatggccatt 3420 agtgcaggcg atgcctatgc ctccaacaaa gcaagtaaag ctgcttccgt ccttctgtat 3480 tctctgtggg cacacacgga actgcatcat gcctacaaga aggctcagtt taagaagaca 3540 gattttgtca acagccggac tgccaaagcc taccactccc ttaaagactg atcaacctct 3600 ggattacaaa atttgtgaaa gattgactgg tattcttaac tatgttgctc cttttacgct 3660 atgtggatac gctgctttaa tgcctttgta tcatgctatt gcttcccgta tggctttcat 3720 tttctcctcc ttgtataaat cctggttgct gtctctttat gaggagttgt ggcccgttgt 3780 caggcaacgt ggcgtggtgt gcactgtgtt tgctgacgca acccccactg gttggggcat 3840 tgccaccacc tgtcagctcc tttccgggac tttcgctttc cccctcccta ttgccacggc 3900 ggaactcatc gccgcctgcc ttgcccgctg ctggacaggg gctcggctgt tgggcactga 3960 caattccgtg gtgttgtcgg ggaaatcatc gtcctttcct tggctgctcg cctgtgttgc 4020 cacctggatt ctgcgcggga cgtccttctg ctacgtccct tcggccctca atccagcgga 4080 ccttccttcc cgcggcctgc tgccggctct gcggcctctt ccgcgtcttc gccttcgccc 4140 tcagacgagt cggatctccc tttgggccgc ctccccgcac tgcccgggtg gcatccctgt 4200 gacccctccc cagtgcctct cctggccctg gaagttgcca ctccagtgcc caccagcctt 4260 gtcctaataa aattaagttg catcattttg tctgactagg tgtccttcta taatattatg 4320 gggtggaggg gggtggtatg gagcaagggg cccaagttgg gaagaaacct gtagggcctg 4380 ctacgtagat aagtagcatg gcgggttaat cattaactac aaggaacccc tagtgatgga 4440 gttggccact ccctctctgc gcgctcgctc gctcactgag gccgggcgac caaaggtcgc 4500 ccgacgcccg ggctttgccc gggcggcctc agtgagcgag cgagcgcgc 4549 <210> SEQ ID NO 15 <211> LENGTH: 4322 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Made in Labe - full polynucleotide sequence of vector genome <400> SEQUENCE: 15 gcgcgctcgc tcgctcactg aggccgcccg ggcaaagccc gggcgtcggg cgacctttgg 60 tcgcccggcc tcagtgagcg agcgagcgcg cagagaggga gtggccaact ccatcactag 120 gggttccttg tagttaatga ttaacccgcc atgctactta tctacgtact cagtccatta 180 ggagccagta gcctggaaga tgtctttacc cccagcatca gttcaagtgg agcagcacat 240 aactcttgcc ctctgccttc caagattctg gtgctgagac ttatggagtg tcttggaggt 300 tgccttctgc cccccaaccc tgctcccagc tggccctccc aggcctgggt tgctggcctc 360 tgctttatca ggattctcaa gagggacagc tggtttatgt tgcatgactg ttccctgcat 420 atctgctctg gttttaaata gcttatctga gcagctggag gaccacatgg gcttatatgg 480 cgtggggtac atgttcctgt agccttgtcc ctggcacctg ccaaaatagc agccaacacc 540 ccccaccccc accgccatcc ccctgcccca cccgtcccct gtcgcacatt cctccctccg 600 cagggctggc tcaccaggcc ccagcccaca tgcctgctta aagccctctc catcctctgc 660 ctcacccagt ccccgctgag actgagcaga cgcctccagg atctgtcggc aggccaccat 720 ggcagccccc ggcgccccag ctgagtacgg ctacatccgg accgtcctgg gccagcagat 780 cctgggacaa ctggacagct ccagcctggc gctgccctcc gaggccaagc tgaagctggc 840 ggggagcagc ggccgcggcg gccagacagt caagagcctg cggatccagg agcaggtgca 900 gcagaccctc gcccggaagg gccgcagctc cgtgggcaac ggaaatcttc accgaaccag 960 cagtgttcct gagtatgtct acaacctaca cttggttgaa aatgattttg ttggaggccg 1020 ttcccctgtt cctaaaacct atgacatgct aaaggctggc acaactgcca cttatgaagg 1080 tcgctgggga agaggaacag cacagtacag ctcccagaag tccgtggaag aaaggtcctt 1140 gaggcatcct ctgaggagac tggagatttc tcctgacagc agcccggaga gggctcacta 1200 cacgcacagc gattaccagt acagccagag aagccaggct gggcacaccc tgcaccacca 1260 agaaagcagg cgggccgccc tcctagtgcc accgagatat gctcgttccg agatcgtggg 1320 ggtcagccgt gctggcacca caagcaggca gcgccacttt gacacatacc acagacagta 1380 ccagcatggc tctgttagcg acaccgtttt tgacagcatc cctgccaacc cggccctgct 1440 cacgtacccc aggccaggga ccagccgcag catgggcaac ctcttggaga aggagaacta 1500 cctgacggca gggctcactg tcgggcaggt caggccgctg gtgcccctgc agcccgtcac 1560 tcagaacagg gcttccaggt cctcctggca tcagagctcc ttccacagca cccgcacgct 1620 gagggaagct gggcccagtg tcgccgtgga ttccagcggg aggagagcgc acttgactgt 1680 cggccaggcg gccgcagggg gaagtgggaa tctgctcact gagagaagca ctttcactga 1740 ctcccagctg gggaatgcag acatggagat gactctggag cgagcagtga gtatgctcga 1800 ggcagaccac atgctgccat ccaggatttc tgctgcagct actttcatac agcacgagtg 1860 cttccagaaa tctgaagctc ggaagagggt taaccagctt cgtggcatcc tcaagcttct 1920 gcagctccta aaagttcaga atgaagacgt tcagcgagct gtgtgtgggg ccttgagaaa 1980 cttagtattt gaagacaatg acaacaaatt ggaggtggct gaactaaatg gggtacctcg 2040 gctgctccag gtgctgaagc aaaccagaga cttggagact aaaaaacaaa taacagacca 2100 tacagtcaat ttaagaagta ggaatggctg gccgggcgcg gtggctcacg cctgtaatcc 2160 cagcactttg ggaggccaag gcgggcggat cacgaggtca ggagttcgag accagcctga 2220 ccaacatggt ttgctgtgga atttgtcatc taatgacaaa ctcaagaatc tcatgataac 2280 agaagcattg cttacgctga cggagaatat catcatcccc ttttctgggt ggcctgaagg 2340 agactaccca aaagcaaatg gtttgctcga ttttgacata ttctacaacg tcactggatg 2400 cctaagaaac atgagttctg ctggcgctga tgggagaaaa gcgatgagaa gatgtgacgg 2460 actcattgac tcactggtcc attatgtcag aggaaccatt gcagattacc agccagatga 2520 caaggccacg gagaattgtg tgtgcattct tcataacctc tcctaccagc tggaggcaga 2580 gctcccagag aaatattccc agaatatcta tattcaaaac cggaatatcc agactgacaa 2640 caacaaaagt attggatgtt ttggcagtcg aagcaggaaa gtaaaagagc aataccagga 2700 cgtgccgatg ccggaggaaa agagcaaccc caagggcgtg gagtggctgt ggcattccat 2760 tgttataagg atgtatctgt ccttgatcgc caaaagtgtc cgcaactaca cacaagaagc 2820 atccttagga gctctgcaga acctcacggc cggaagtgga ccaatgccga catcagtggc 2880 tcagacagtt gtccagaagg aaagtggcct gcagcacacc cgaaagatgc tgcatgttgg 2940 tgacccaagt gtgaaaaaga cagccatctc gctgctgagg aatctgtccc ggaatctttc 3000 tctgcagaat gaaattgcca aagaaactct ccctgatttg gtttccatca ttcctgacac 3060 agtcccgagt actgaccttc tcattgaaac tacagcctct gcctgttaca cattgaacaa 3120 cataatccaa aacagttacc agaatgcacg cgaccttcta aacaccgggg gcatccagaa 3180 aattatggcc attagtgcag gcgatgccta tgcctccaac aaagcaagta aagctgcttc 3240 cgtccttctg tattctctgt gggcacacac ggaactgcat catgcctaca agaaggctca 3300 gtttaagaag acagattttg tcaacagccg gactgccaaa gcctaccact cccttaaaga 3360 ctgatcaacc tctggattac aaaatttgtg aaagattgac tggtattctt aactatgttg 3420 ctccttttac gctatgtgga tacgctgctt taatgccttt gtatcatgct attgcttccc 3480 gtatggcttt cattttctcc tccttgtata aatcctggtt gctgtctctt tatgaggagt 3540 tgtggcccgt tgtcaggcaa cgtggcgtgg tgtgcactgt gtttgctgac gcaaccccca 3600 ctggttgggg cattgccacc acctgtcagc tcctttccgg gactttcgct ttccccctcc 3660 ctattgccac ggcggaactc atcgccgcct gccttgcccg ctgctggaca ggggctcggc 3720 tgttgggcac tgacaattcc gtggtgttgt cggggaaatc atcgtccttt ccttggctgc 3780 tcgcctgtgt tgccacctgg attctgcgcg ggacgtcctt ctgctacgtc ccttcggccc 3840 tcaatccagc ggaccttcct tcccgcggcc tgctgccggc tctgcggcct cttccgcgtc 3900 ttcgccttcg ccctcagacg agtcggatct ccctttgggc cgcctccccg cactgcccgg 3960 gtggcatccc tgtgacccct ccccagtgcc tctcctggcc ctggaagttg ccactccagt 4020 gcccaccagc cttgtcctaa taaaattaag ttgcatcatt ttgtctgact aggtgtcctt 4080 ctataatatt atggggtgga ggggggtggt atggagcaag gggcccaagt tgggaagaaa 4140 cctgtagggc ctgctacgta gataagtagc atggcgggtt aatcattaac tacaaggaac 4200 ccctagtgat ggagttggcc actccctctc tgcgcgctcg ctcgctcact gaggccgggc 4260 gaccaaaggt cgcccgacgc ccgggctttg cccgggcggc ctcagtgagc gagcgagcgc 4320 gc 4322 <210> SEQ ID NO 16 <211> LENGTH: 13 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Kozak sequence motif <400> SEQUENCE: 16 gccgccrcca ugg 13 <210> SEQ ID NO 17 <400> SEQUENCE: 17 000 <210> SEQ ID NO 18 <211> LENGTH: 10 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Kozak sequence motif <400> SEQUENCE: 18 gacaccaugg 10 <210> SEQ ID NO 19 <400> SEQUENCE: 19 000

<210> SEQ ID NO 20 <211> LENGTH: 141 <212> TYPE: DNA <213> ORGANISM: Adeno-associated virus <400> SEQUENCE: 20 cctgcaggca gctgcgcgct cgctcgctca ctgaggccgc ccgggcaaag cccgggcgtc 60 gggcgacctt tggtcgcccg gcctcagtga gcgagcgagc gcgcagagag ggagtggcca 120 actccatcac taggggttcc t 141 <210> SEQ ID NO 21 <211> LENGTH: 168 <212> TYPE: DNA <213> ORGANISM: Adeno-associated virus 2 <400> SEQUENCE: 21 gcgcgctcgc tcgctcactg aggccgcccg ggcaaagccc gggcgtcggg cgacctttgg 60 tcgcccggcc tcagtgagcg agcgagcgcg cagagaggga gtggccaact ccatcactag 120 gggttccttg tagttaatga ttaacccgcc atgctactta tctacgta 168 <210> SEQ ID NO 22 <211> LENGTH: 170 <212> TYPE: DNA <213> ORGANISM: Adeno-associated virus <400> SEQUENCE: 22 ctgcgcgctc gctcgctcac tgaggccgcc cgggcaaagc ccgggcgtcg ggcgaccttt 60 ggtcgcccgg cctcagtgag cgagcgagcg cgcagagagg gagtggccaa ctccatcact 120 aggggttcct tgtagttaat gattaacccg ccatgctact tatctacgta 170 <210> SEQ ID NO 23 <211> LENGTH: 145 <212> TYPE: DNA <213> ORGANISM: Adeno-associated virus <400> SEQUENCE: 23 ttggccactc cctctctgcg cgctcgctcg ctcactgagg ccgcccgggc aaagcccggg 60 cgtcgggcga cctttggtcg cccggcctca gtgagcgagc gagcgcgcag agagggagtg 120 gccaactcca tcactagggg ttcct 145 <210> SEQ ID NO 24 <211> LENGTH: 141 <212> TYPE: DNA <213> ORGANISM: Adeno-associated viurs <400> SEQUENCE: 24 aggaacccct agtgatggag ttggccactc cctctctgcg cgctcgctcg ctcactgagg 60 ccgggcgacc aaaggtcgcc cgacgcccgg gctttgcccg ggcggcctca gtgagcgagc 120 gagcgcgcag ctgcctgcag g 141 <210> SEQ ID NO 25 <211> LENGTH: 168 <212> TYPE: DNA <213> ORGANISM: Adeno-associated virus 2 <400> SEQUENCE: 25 tacgtagata agtagcatgg cgggttaatc attaactaca aggaacccct agtgatggag 60 ttggccactc cctctctgcg cgctcgctcg ctcactgagg ccgggcgacc aaaggtcgcc 120 cgacgcccgg gctttgcccg ggcggcctca gtgagcgagc gagcgcgc 168 <210> SEQ ID NO 26 <211> LENGTH: 133 <212> TYPE: DNA <213> ORGANISM: Adeno-associated virus 2 <400> SEQUENCE: 26 aggaacccct agtgatggag actccctctc tgcgcgctcg ctcgctcact gaggccgggc 60 gaccaaaggt cgcccgacgc ccgggctttg cccgggcggc ctcagtgagc gagcgagcgc 120 gcagagaggg agt 133 <210> SEQ ID NO 27 <211> LENGTH: 124 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Made in Lab - vector filler sequence <400> SEQUENCE: 27 gcggcaattc agtcgataac tataacggtc ctaaggtagc gatttaaata cgcgctctct 60 taaggtagcc ccgggacgcg tcaattgact acaaaccgag tatctgcaga gggccctgcg 120 tatg 124 <210> SEQ ID NO 28 <211> LENGTH: 84 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Made in Lab - vector filler sequence <400> SEQUENCE: 28 cttctgaggc ggaaagaacc agatcctctc ttaaggtagc atcgagattt aaattaggga 60 taacagggta atggcgcggg ccgc 84 <210> SEQ ID NO 29 <211> LENGTH: 63 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Made in Lab - vector filler sequence <400> SEQUENCE: 29 gttacccagg ctggagtgca gtggcacatt tctgctcact gcaacctcct cctccctggg 60 ttc 63 <210> SEQ ID NO 30 <211> LENGTH: 573 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Made in lab - CAG promoter in part Human betaherpesvirus 5 <400> SEQUENCE: 30 acttacggta aatggcccgc ctggctgacc gcccaacgac ccccgcccat tgacgtcaat 60 aatgacgtat gttcccatag taacgccaat agggactttc cattgacgtc aatgggtgga 120 gtatttacgg taaactgccc acttggcagt acatcaagtg tatcatatgc caagtacgcc 180 ccctattgac gtcaatgacg gtaaatggcc cgcctggcat tatgcccagt acatgacctt 240 atgggacttt cctacttggc agtacatcta cgtattagtc atcgctatta ccatggtcga 300 ggtgagcccc acgttctgct tcactctccc catctccccc ccctccccac ccccaatttt 360 gtatttattt attttttaat tattttgtgc agcgatgggg gcgggggggg ggggggcgcg 420 cgccaggcgg ggcggggcgg ggcgaggggc ggggcggggc gaggcggaga ggtgcggcgg 480 cagccaatca gagcggcgcg ctccgaaagt ttccttttat ggcgaggcgg cggcggcggc 540 ggccctataa aaagcgaagc gcgcggcggg cgg 573 <210> SEQ ID NO 31 <211> LENGTH: 771 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Made in Lab - MHCK7 promoter <400> SEQUENCE: 31 acccttcaga ttaaaaataa ctgaggtaag ggcctgggta ggggaggtgg tgtgagacgc 60 tcctgtctct cctctatctg cccatcggcc ctttggggag gaggaatgtg cccaaggact 120 aaaaaaaggc catggagcca gaggggcgag ggcaacagac ctttcatggg caaaccttgg 180 ggccctgctg tctagcatgc cccactacgg gtctaggctg cccatgtaag gaggcaaggc 240 ctggggacac ccgagatgcc tggttataat taacccagac atgtggctgc cccccccccc 300 ccaacacctg ctgcctctaa aaataaccct gtccctggtg gatcccctgc atgcgaagat 360 cttcgaacaa ggctgtgggg gactgagggc aggctgtaac aggcttgggg gccagggctt 420 atacgtgcct gggactccca aagtattact gttccatgtt cccggcgaag ggccagctgt 480 cccccgccag ctagactcag cacttagttt aggaaccagt gagcaagtca gcccttgggg 540 cagcccatac aaggccatgg ggctgggcaa gctgcacgcc tgggtccggg gtgggcacgg 600 tgcccgggca acgagctgaa agctcatctg ctctcagggg cccctccctg gggacagccc 660 ctcctggcta gtcacaccct gtaggctcct ctatataacc caggggcaca ggggctgccc 720 tcattctacc accacctcca cagcacagac agacactcag gagccagcca g 771 <210> SEQ ID NO 32 <211> LENGTH: 544 <212> TYPE: DNA <213> ORGANISM: Homo sapiens <400> SEQUENCE: 32 ctcagtccat taggagccag tagcctggaa gatgtcttta cccccagcat cagttcaagt 60 ggagcagcac ataactcttg ccctctgcct tccaagattc tggtgctgag acttatggag 120 tgtcttggag gttgccttct gccccccaac cctgctccca gctggccctc ccaggcctgg 180 gttgctggcc tctgctttat caggattctc aagagggaca gctggtttat gttgcatgac 240 tgttccctgc atatctgctc tggttttaaa tagcttatct gagcagctgg aggaccacat 300 gggcttatat ggcgtggggt acatgttcct gtagccttgt ccctggcacc tgccaaaata 360 gcagccaaca ccccccaccc ccaccgccat ccccctgccc cacccgtccc ctgtcgcaca 420 ttcctccctc cgcagggctg gctcaccagg ccccagccca catgcctgct taaagccctc 480 tccatcctct gcctcaccca gtccccgctg agactgagca gacgcctcca ggatctgtcg 540 gcag 544 <210> SEQ ID NO 33 <211> LENGTH: 502 <212> TYPE: DNA <213> ORGANISM: Homo sapiens <400> SEQUENCE: 33 ctcagtccat taggagccag tagcctggaa gatgtcttta cccccagcat cagttcaagt 60 ggagcagcac ataactcttg ccctctgcct tccaagattc tggtgctgag acttatggag 120 tgtcttggag gttgccttct gccccccaac cctgctccca gctggccctc ccaggcctgg 180 gttgctggcc tctgctttat caggattctc aagagggaca gctggtttat gttgcatgac 240

tgttccctgc atatctgctc tggttttaaa tagcttatct gagcagctgg aggaccacat 300 gggcttatat ggcgtggggt acatgttcct gtagccttgt ccctggcacc tgccaaaata 360 gcagccaaca ccccccaccc ccaccgccat ccccctgccc cacccgtccc ctgtcgcaca 420 ttcctccctc cgcagggctg gctcaccagg ccccagccca catgcctgct taaagccctc 480 tccatcctct gcctcaccca gt 502 <210> SEQ ID NO 34 <211> LENGTH: 5464 <212> TYPE: DNA <213> ORGANISM: Mus musculus <400> SEQUENCE: 34 ggtaccggat cctgcaaggt cacacaaggg tctccaccca ccaggtgccc tagtctcaat 60 ttcagtttcc atgccttgtt ctcacaatgc tggcctcccc agagctaatt tggactttgt 120 ttttatttca aaagggcctg aatgaggagt agatcttgtg ctacccagct ctaagggtgc 180 ccgtgaagcc ctcagacctg gagcctttgc aacagccctt taggtggaag cagaataaag 240 caattttcct taaagccaaa atcctgcctc tagactcttc ttctctgacc tcggtccctg 300 ggctctaggg tggggaggtg gggcttggaa gaagaaggtg gggaagtggc aaaagccgat 360 ccctagggcc ctgtgaagtt cggagccttc cctgtacagc actggctcat agatcctcct 420 ccagccaaac atagcaagaa gtgatacctc ctttgtgact tccccaggcc cagtacctgt 480 caggttgaaa caggatttag agaagcctct gaactcacct gaactctgaa gctcatccac 540 caagcaagca cctaggtgcc actgctagtt agtatcctac gctgataata tgcagagctg 600 ggccacagaa gtcctggggt gtaggaactg accagtgact tttcagtcgg caaaggtatg 660 accccctcag cagatgtagt aatgtcccct tagatcccat cccaggcagg tctctaagag 720 gacatgggat gagagatgta gtcatgtggc attccaaaca cagctatcca cagtgtccct 780 tgccccttcc acttagccag gaggacagta accttagcct atctttcttc ctccccatcc 840 tcccaggaca caccccctgg tctgcagtat tcatttcttc cttcacgtcc cctctgtgac 900 ttccatttgc aaggcttttg acctctgcag ctgctggaag atagagtttg gccctaggtg 960 tggcaagcca tctcaagaga aagcagacaa cagggggacc agattttgga aggatcagga 1020 actaaatcac tggcgggcct gggggtagaa aaaagagtga gtgagtccgc tccagctaag 1080 ccaagctagt ccccgagata ctctgccaca gctgggctgc tcggggtagc tttaggaatg 1140 tgggtctgaa agacaatggg attggaagac atctctttga gtctcccctc aaccccacct 1200 acagacacac tcgtgtgtgg ccagactcct gttcaacagc cctctgtgtt ctgaccactg 1260 agctaggcaa ccagagcatg ggccctgtgc tgaggatgaa gagttggtta ccaatagcaa 1320 aaacagcagg ggagggagaa cagagaacga aataaggaag gaagaaggaa aggccagtca 1380 atcagatgca gtcagaagag atgggaagcc aacacacagc ttgagcagag gaaacagaaa 1440 agggagagat tctgggcata aggaggccac agaaagaaga gcccaggccc cccaagtctc 1500 ctctttatac cctcatcccg tctcccaatt aagcccactc ttcttcctag atcagacctg 1560 agctgcagcg aagagacccg tagggaggat cacactggat gaaggagatg tgtggagaag 1620 tccagggaac ctaagagcca gagcctaaaa gagcaagaga taaaggtgct tcaaaggtgg 1680 ccaggctgtg cacacagagg gtcgaggact ggtggtagag cctcaagata aggatgatgc 1740 tcagaatggg cggggggggg gattctgggg gggggagaga gaaggtgaga aggagcctgg 1800 aacagagaat ctggaagcgc tggaaacgat accataaagg gaagaaccca ggctaccttt 1860 agatgtaaat catgaaagac agggagaagg gaagctggag agagtagaag gaccccgggg 1920 caagacattg aagcaaggac aagccaggtt gagcgctccg tgaaatcagc ctgctgaagg 1980 cagagccctg gtatgagcac cagaacagca gaggctaggg ttaatgtcga gacagggaac 2040 agaaggtaga cacaggaaca gacagagacg ggggagccag gtaacaaagg aatggtcctt 2100 ctcacctgtg gccagagcgt ccatctgtgt ccacatactc tagaatgttc atcagactgc 2160 agggctggct tgggaggcag ctggaaagag tatgtgagag ccaggggaga caagggggcc 2220 taggaaagga agaagagggc aaaccaggcc acacaagagg gcagagccca gaactgagtt 2280 aactccttcc ttgttgcatc ttccatagga ggcagtggga actctgtgac caccatcccc 2340 catgagcccc cactacccat accaagtttg gcctgagtgg cattctaggt tccctgagga 2400 cagagcctgg cctttgtctc ttggacctga cccaagctga cccaatgttc tcagtacctt 2460 atcatgccct caagagcttg agaaccaggc agtgacatat taggccatgg gctaaccctg 2520 gagcttgcac acaggagcct caagtgacct ccagggacac agctgcagac aggtggcctt 2580 tatccccaaa gagcaaccat ttggcatagg tggctgcaaa tgggaatgca aggttgaatc 2640 aggtcccttc aagaatactg catgcaagac ctaagacccc tggagagagg ggtatgctcc 2700 tgcccccacc caccataagg ggagtgaact atcctagggg gctggcgacc ttggggagac 2760 accacattac tgagagtgct gagcccagaa aaactgaccg ccctgtgtcc tgcccacctc 2820 cacactctag agctatattg agaggtgaca gtagataggg tgggagctgg tagcagggag 2880 agtgttcctg ggtgtgaggg tgtaggggaa agccagagca ggggagtctg gctttgtctc 2940 ctgaacacaa tgtctactta gttataacag gcatgacctg ctaaagaccc aacatctacg 3000 acctctgaaa agacagcagc cctggaggac aggggttgtc tctgagcctt gggtgcttga 3060 tggtgccaca aaggagggca tgagtgtgag tataaggccc caggagcgtt agagaagggc 3120 acttgggaag gggtcagtct gcagagcccc tatccatgga atctggagcc tggggccaac 3180 tggtgtaaat ctctgggcct gccaggcatt caaagcagca cctgcatcct ctggcagcct 3240 ggggaggcgg aagggagcaa ccccccactt ataccctttc tccctcagcc ccaggattaa 3300 cacctctggc cttccccctt cccacctccc atcaggagtg gagggttgca gagggagggt 3360 aaaaacctac atgtccaaac atcatggtgc acgatatatg gatcagtatg tgtagaggca 3420 agaaaggaaa tctgcaggct taactgggtt aatgtgtaaa gtctgtgtgc atgtgtgtgt 3480 gtctgactga aaacgggcat ggctgtgcag ctgttcagtt ctgtgcgtga ggttaccaga 3540 ctgcaggttt gtgtgtaaat tgcccaaggc aaagtgggtg aatcccttcc atggtttaaa 3600 gagattggat gatggcctgc atctcaagga ccatggaaaa tagaatggac actctatatg 3660 tgtctctaag ctaaggtagc aaggtctttg gaggacacct gtctagagat gtgggcaaca 3720 gagactacag acagtatctg tacagagtaa ggagagagag gagggggtgt agaattctct 3780 tactatcaaa gggaaactga gtcgtgcacc tgcaaagtgg atgctctccc tagacatcat 3840 gactttgtct ctggggagcc agcactgtgg aacttcaggt ctgagagagt aggaggctcc 3900 cctcagcctg aagctatgca gatagccagg gttgaaaggg ggaagggaga gcctgggatg 3960 ggagcttgtg tgttggaggc aggggacaga tattaagcct ggaagagaag gtgaccctta 4020 cccagttgtt caactcaccc ttcagattaa aaataactga ggtaagggcc tgggtagggg 4080 aggtggtgtg agacgctcct gtctctcctc tatctgccca tcggcccttt ggggaggagg 4140 aatgtgccca aggactaaaa aaaggccatg gagccagagg ggcgagggca acagaccttt 4200 catgggcaaa ccttggggcc ctgctgtcct cctgtcacct ccagagccaa gggatcaaag 4260 gaggaggagc caggacagga gggaagtggg agggagggtc ccagcagagg actccaaatt 4320 taggcagcag gcatatggga tgggatataa aggggctgga gcactgagag ctgtcagaga 4380 tttctccaac ccaggtaaga gggagtttcg ggtgggggct cttcacccac accagacctc 4440 tccccaccta gaaggaaact gcctttcctg gaagtggggt tcaggccggt cagagatctg 4500 acagggtggc cttccaccag cctgggaagt tctcagtggc aggaggtttc cacaagaaac 4560 actggatgcc ccttccctta cgctgtcttc tccatcttcc tcctggggat gctcctcccc 4620 gtcttggttt atcttggctc ttcgtcttca gcaagatttg ccctgtgctg tccactccat 4680 ctttctctac tgtctccgtg ccttgccttg ccttcttgcg tgtccttcct ttccacccat 4740 ttctcacttc accttttctc cccttctcat ttgtattcat ccttccttcc ttccttcctt 4800 ccttccttcc ttccttcctt ccttcctttc tcccttcctt ccttccttcc ttccttcctt 4860 ccttccttcc ttcctgtgtc agagtgctga gaatcacacc tggggttccc acccttatgt 4920 aaacaatctt ccagtgagcc acagcttcag tgctgctggg tgctctctta ccttcctcac 4980 cccctggctt gtcctgttcc atcctggtca ggatctctag attggtctcc cagcctctgc 5040 tactcctctt cctgcctgtt cctctctctg tccagctgcg ccactgtggt gcctcgttcc 5100 agctgtggtc cacattcttc aggattctct gaaaagttaa ccaggtgaga atgtttcccc 5160 tgtagacagc agatcacgat tctcccggaa gtcaggcttc cagccctctc tttctctgcc 5220 cagctgcccg gcactcttag caaacctcag gcacccttac cccacataga cctctgacag 5280 agaagcaggc actttacatg gagtcctggt gggagagcca taggctacgg tgtaaaagag 5340 gcagggaagt ggtggtgtag gaaagtcagg acttcacata gaagcctagc ccacaccaga 5400 aatgacagac agatccctcc tatctccccc ataagagttt gagtcgaccc gcggccccga 5460 attg 5464 <210> SEQ ID NO 35 <211> LENGTH: 413 <212> TYPE: DNA <213> ORGANISM: Gallus gallus <400> SEQUENCE: 35 gggataaaag cagtctgggc tttcacatga cagcatctgg ggctgcggca gagggtcggg 60 tccgaagcgc tgccttatca gcgtccccag ccctgggagg tgacagctgg ctggcttgtg 120 tcagcccctc gggcactcac gtatctccgt ccgacgggtt taaaatagca aaactctgag 180 gccacacaat agcttgggct tatatgggct cctgtggggg aagggggagc acggaggggg 240 ccggggccgc tgctgccaaa atagcagctc acaagtgttg cattcctctc tgggcgccgg 300 gcacattcct gctggctctg cccgccccgg ggtgggcgcc ggggggacct taaagcctct 360 gccccccaag gagcccttcc cagacagccg ccggcaccca ccgctccgtg gga 413 <210> SEQ ID NO 36 <211> LENGTH: 1090 <212> TYPE: DNA <213> ORGANISM: Homo sapiens <400> SEQUENCE: 36 ctctcagccc tggaagtcct tgctcacagc cgaggcgccg agagcgcttg ctctgcccag 60 atctgcgcga gtctggcgcc cgcgctctga acggcgtcgc tgcccagccc ccttccccgg 120 gaggtgggag cggccaccca gggccccgtg gctgcccttg taaggaggcg aggcccgagg 180 acacccgaga cgcccggtta taattaacca ggacacgtgg cgaacccccc tccaacacct 240 gcccccgaac ccccccatac ccagcgcctc gggtctcggc ctttgcggca gaggagacag 300 caaagcgccc tctaaaaata actcctttcc cggcgaccga gaccctccct gtcccccgca 360 cagcggaaat ctcccagtgg caccgagggg gcgagggtta agtggggggg agggtgacca 420 ccgcctccca cccttgccct gagtttgaat ctctccaact cagccagcct cagtttcccc 480 tccactcagt ccctaggagg aaggggcgcc caagcgcggg tttctggggt tagactgccc 540

tccattgcaa ttggtccttc tcccggcctc tgcttcctcc agctcacagg gtatctgctc 600 ctcctggagc cacaccttgg ttccccgagg tgccgctggg actcgggtag gggtgagggc 660 ccagggggca cagggggagc cgagggccac aggaagggct ggtggctgaa ggagactcag 720 gggccagggg acggtggctt ctacgtgctt gggacgttcc cagccaccgt cccatgttcc 780 cggcgggggg ccagctgtcc ccaccgccag cccaactcag cacttggtca gggtatcagc 840 ttggtggggg ggcgtgagcc cagcccctgg ggcggctcag cccatacaag gccatggggc 900 tgggcgcaaa gcatgcctgg gttcagggtg ggtatggtgc gggagcaggg aggtgagagg 960 ctcagctgcc ctccagaact cctccctggg gacaacccct cccagccaat agcacagcct 1020 aggtccccct atataaggcc acggctgctg gcccttcctt tgggtcagtg tcacctccag 1080 gatacagaca 1090 <210> SEQ ID NO 37 <211> LENGTH: 253 <212> TYPE: DNA <213> ORGANISM: Homo sapiens <400> SEQUENCE: 37 gcccagcacc ccaaggcggc caacgccaaa actctccctc ctcctcttcc tcaatctcgc 60 tctcgctctt tttttttttc gcaaaaggag gggagagggg gtaaaaaaat gctgcactgt 120 gcggcgaagc cggtgagtga gcggcgcggg gccaatcagc gtgcgccgtt ccgaaagttg 180 ccttttatgg ctcgagcggc cgcggcggcg ccctataaaa cccagcggcg cgacgcgcca 240 ccaccgccga gtc 253 <210> SEQ ID NO 38 <211> LENGTH: 281 <212> TYPE: DNA <213> ORGANISM: Gallus gallus <400> SEQUENCE: 38 ggtcgaggtg agccccacgt tctgcttcac tctccccatc tcccccccct ccccaccccc 60 aattttgtat ttatttattt tttaattatt ttgtgcagcg atgggggcgg gggggggggg 120 ggcgcgcgcc aggcggggcg gggcggggcg aggggcgggg cggggcgagg cggagaggtg 180 cggcggcagc caatcagagc ggcgcgctcc gaaagtttcc ttttatggcg aggcggcggc 240 ggcggcggcc ctataaaaag cgaagcgcgc ggcgggcggg a 281 <210> SEQ ID NO 39 <211> LENGTH: 220 <212> TYPE: DNA <213> ORGANISM: Human betaherpesvirus 5 <400> SEQUENCE: 39 tggtgatgcg gttttggcag tacaccaatg ggcgtggata gcggtttgac tcacggggat 60 ttccaagtct ccaccccatt gacgtcaatg ggagtttgtt ttggcaccaa aatcaacggg 120 actttccaaa atgtcgtaat aaccccgccc cgttgacgca aatgggcggt aggcgtgtac 180 ggtgggaggt ctatataagc agagctcgtt tagtgaaccg 220 <210> SEQ ID NO 40 <211> LENGTH: 583 <212> TYPE: DNA <213> ORGANISM: Human betaherpesvirus 5 <400> SEQUENCE: 40 tagttattaa tagtaatcaa ttacggggtc attagttcat agcccatata tggagttccg 60 cgttacataa cttacggtaa atggcccgcc tggctgaccg cccaacgacc cccgcccatt 120 gacgtcaata atgacgtatg ttcccatagt aacgccaata gggactttcc attgacgtca 180 atgggtggag tatttacggt aaactgccca cttggcagta catcaagtgt atcatatgcc 240 aagtacgccc cctattgacg tcaatgacgg taaatggccc gcctggcatt atgcccagta 300 catgacctta tgggactttc ctacttggca gtacatctac gtattagtca tcgctattac 360 catggtgatg cggttttggc agtacatcaa tgggcgtgga tagcggtttg actcacgggg 420 atttccaagt ctccacccca ttgacgtcaa tgggagtttg ttttggcacc aaaatcaacg 480 ggactttcca aaatgtcgta acaactccgc cccattgacg caaatgggcg gtaggcgtgt 540 acggtgggag gtctatataa gcagagctgg tttagtgaac cgt 583 <210> SEQ ID NO 41 <211> LENGTH: 508 <212> TYPE: DNA <213> ORGANISM: Human betaherpesvirus 5 <400> SEQUENCE: 41 cgttacataa cttacggtaa atggcccgcc tggctgaccg cccaacgacc cccgcccatt 60 gacgtcaata atgacgtatg ttcccatagt aacgccaata gggactttcc attgacgtca 120 atgggtggag tatttacggt aaactgccca cttggcagta catcaagtgt atcatatgcc 180 aagtacgccc cctattgacg tcaatgacgg taaatggccc gcctggcatt atgcccagta 240 catgacctta tgggactttc ctacttggca gtacatctac gtattagtca tcgctattac 300 catggtgatg cggttttggc agtacatcaa tgggcgtgga tagcggtttg actcacgggg 360 atttccaagt ctccacccca ttgacgtcaa tgggagtttg ttttggcacc aaaatcaacg 420 ggactttcca aaatgtcgta acaactccgc cccattgacg caaatgggcg gtaggcgtgt 480 acggtgggag gtctatataa gcagagct 508 <210> SEQ ID NO 42 <211> LENGTH: 573 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Made in lab - CAG promoter in part Human betaherpesvirus 5 <400> SEQUENCE: 42 acttacggta aatggcccgc ctggctgacc gcccaacgac ccccgcccat tgacgtcaat 60 aatgacgtat gttcccatag taacgccaat agggactttc cattgacgtc aatgggtgga 120 gtatttacgg taaactgccc acttggcagt acatcaagtg tatcatatgc caagtacgcc 180 ccctattgac gtcaatgacg gtaaatggcc cgcctggcat tatgcccagt acatgacctt 240 atgggacttt cctacttggc agtacatcta cgtattagtc atcgctatta ccatggtcga 300 ggtgagcccc acgttctgct tcactctccc catctccccc ccctccccac ccccaatttt 360 gtatttattt attttttaat tattttgtgc agcgatgggg gcgggggggg ggggggcgcg 420 cgccaggcgg ggcggggcgg ggcgaggggc ggggcggggc gaggcggaga ggtgcggcgg 480 cagccaatca gagcggcgcg ctccgaaagt ttccttttat ggcgaggcgg cggcggcggc 540 ggccctataa aaagcgaagc gcgcggcggg cgg 573 <210> SEQ ID NO 43 <211> LENGTH: 580 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Made in lab - CAG promoter in part Human betaherpesvirus 5 <400> SEQUENCE: 43 cgttacataa cttacggtaa atggcccgcc tggctgaccg cccaacgacc cccgcccatt 60 gacgtcaata atgacgtatg ttcccatagt aacgccaata gggactttcc attgacgtca 120 atgggtggag tatttacggt aaactgccca cttggcagta catcaagtgt atcatatgcc 180 aagtacgccc cctattgacg tcaatgacgg taaatggccc gcctggcatt atgcccagta 240 catgacctta tgggactttc ctacttggca gtacatctac gtattagtca tcgctattac 300 catgtcgagg tgagccccac gttctgcttc actctcccca tctccccccc ctccccaccc 360 ccaattttgt atttatttat tttttaatta ttttgtgcag cgatgggggc gggggggggg 420 ggggcgcgcg ccaggcgggg cggggcgggg cgaggggcgg ggcggggcga ggcggagagg 480 tgcggcggca gccaatcaga gcggcgcgct ccgaaagttt ccttttatgg cgaggcggcg 540 gcggcggcgg ccctataaaa agcgaagcgc gcggcgggcg 580 <210> SEQ ID NO 44 <211> LENGTH: 455 <212> TYPE: DNA <213> ORGANISM: Homo sapiens <400> SEQUENCE: 44 caacctttgg agctaagcca gcaatggtag agggaagatt ctgcacgtcc cttccaggcg 60 gcctccccgt caccaccccc cccaacccgc cccgaccgga gctgagagta attcatacaa 120 aaggactcgc ccctgccttg gggaatccca gggaccgtcg ttaaactccc actaacgtag 180 aacccagaga tcgctgcgtt cccgccccct cacccgcccg ctctcgtcat cactgaggtg 240 gagaatagca tgcgtgaggc tccggtgccc gtcagtgggc agagcgcaca tcgcccacag 300 tccccgagaa gttgggggga ggggtcggca attgaacggg tgcctagaga aggtggcgcg 360 gggtaaactg ggaaagtgat gtcgtgtact ggctccgcct ttttcccgag ggtgggggag 420 aaccgtatat aagtgcagta gtcgccgtga acgtt 455 <210> SEQ ID NO 45 <400> SEQUENCE: 45 000 <210> SEQ ID NO 46 <400> SEQUENCE: 46 000 <210> SEQ ID NO 47 <400> SEQUENCE: 47 000 <210> SEQ ID NO 48 <211> LENGTH: 281 <212> TYPE: DNA <213> ORGANISM: Homo sapiens <400> SEQUENCE: 48 acttgtggac aaagtttgct ctattccacc tcctccaggc cctccttggg tccatcaccc 60 caggggtgct gggtccatcc cacccccagg cccacacagg cttgcagtat tgtgtgcggt 120 atggtcaggg cgtccgagag caggtttcgc agtggaaggc aggcaggtgt tggggaggca 180 gttaccgggg caacgggaac agggcgtttt ggaggtggtt gccatgggga cctggatgct 240 gacgaaggct cgcgaggctg tgagcagcca cagtgccctg c 281

<210> SEQ ID NO 49 <400> SEQUENCE: 49 000 <210> SEQ ID NO 50 <211> LENGTH: 293 <212> TYPE: DNA <213> ORGANISM: Human betaherpesvirus 5 <400> SEQUENCE: 50 acttacggta aatggcccgc ctggctgacc gcccaacgac ccccgcccat tgacgtcaat 60 aatgacgtat gttcccatag taacgccaat agggactttc cattgacgtc aatgggtgga 120 gtatttacgg taaactgccc acttggcagt acatcaagtg tatcatatgc caagtacgcc 180 ccctattgac gtcaatgacg gtaaatggcc cgcctggcat tatgcccagt acatgacctt 240 atgggacttt cctacttggc agtacatcta cgtattagtc atcgctatta cca 293 <210> SEQ ID NO 51 <211> LENGTH: 953 <212> TYPE: DNA <213> ORGANISM: Homo sapiens <400> SEQUENCE: 51 cgcgtccgcc cgcgagcaca gagcctcgcc tttgccgatc cgccgcccgt ccacacccgc 60 cgccaggtaa gcccggccag ccgaccgggg catgcggccg cggcccttcg cccgtgcaga 120 gccgccgtct gggccgcagc ggggggcgca tggggcggaa ccggaccgcc gtggggggcg 180 cgggagaagc ccctgggcct ccggagatgg gggacacccc acgccagttc gcaggcgcga 240 ggccgcgctc gggcgggcgc gctccggggg tgccgctctc ggggcggggg caaccggcgg 300 ggtctttgtc tgagccgggc tcttgccaat ggggatcgca cggtgggcgc ggcgtagccc 360 ccgtcaggcc cggtgggggc tggggcgcca tgcgcgtgcg cgctggtcct ttgggcgcta 420 actgcgtgcg cgctgggaat tggcgctaat tgcgcgtgcg cgctgggact caatggcgct 480 aatcgcgcgt gcgttctggg gcccgggcgc ttgcgccact tcctgcccga gccgctggcg 540 cccgagggtg tggccgctgc gtgcgcgcgc gcgacccggt cgctgtttga accgggcgga 600 ggcggggctg gcgcccggtt gggagggggt tggggcctgg cttcctgccg cgcgccgcgg 660 ggacgcctcc gaccagtgtt tgccttttat ggtaataacg cggccggccc ggcttccttt 720 gtccccaatc tgggcgcgcg ccggcgcccc ctggcggcct aaggactcgg cgcgccggaa 780 gtggccaggg cggcagcggc tgctcttggc ggccccgagg tgactatagc cttcttttgt 840 gtcttgatag ttcgccagcc tctgctaacc atgttcatgc cttcttcttt ttcctacagc 900 tcctgggcaa cgtgctggtt attgtgctgt ctcatcattt tggcaaagaa ttc 953 <210> SEQ ID NO 52 <211> LENGTH: 1068 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Made in Lab - Chicken beta-actin exon/intron plus rabbit globin intron <400> SEQUENCE: 52 gtcgctgcgc gctgccttcg ccccgtgccc cgctccgccg ccgcctcgcg ccgcccgccc 60 cggctctgac tgaccgcgtt actcccacag gtgagcgggc gggacggccc ttctcctccg 120 ggctgtaatt agcgcttggt ttaatgacgg cttgtttctt ttctgtggct gcgtgaaagc 180 cttgaggggc tccgggaggg ccctttgtgc ggggggagcg gctcgggggg tgcgtgcgtg 240 tgtgtgtgcg tggggagcgc cgcgtgcggc tccgcgctgc ccggcggctg tgagcgctgc 300 gggcgcggcg cggggctttg tgcgctccgc agtgtgcgcg aggggagcgc ggccgggggc 360 ggtgccccgc ggtgcggggg gggctgcgag gggaacaaag gctgcgtgcg gggtgtgtgc 420 gtgggggggt gagcaggggg tgtgggcgcg tcggtcgggc tgcaaccccc cctgcacccc 480 cctccccgag ttgctgagca cggcccggct tcgggtgcgg ggctccgtac ggggcgtggc 540 gcggggctcg ccgtgccggg cggggggtgg cggcaggtgg gggtgccggg cggggcgggg 600 ccgcctcggg ccggggaggg ctcgggggag gggcgcggcg gcccccggag cgccggcggc 660 tgtcgaggcg cggcgagccg cagccattgc cttttatggt aatcgtgcga gagggcgcag 720 ggacttcctt tgtcccaaat ctgtgcggag ccgaaatctg ggaggcgccg ccgcaccccc 780 tctagcgggc gcggggcgaa gcggtgcggc gccggcagga aggaaatggg cggggagggc 840 cttcgtgcgt cgccgcgccg ccgtcccctt ctccctctcc agcctcgggg ctgtccgcgg 900 ggggacggct gccttcgggg gggacggggc agggcggggt tcggcttctg gcgtgtgacc 960 ggcggctcta gagcctctgc taaccatgtt catgccttct tctttttcct acagctcctg 1020 ggcaacgtgc tggttattgt gctgtctcat cattttggca aagaattc 1068 <210> SEQ ID NO 53 <211> LENGTH: 149 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Made in Lab - chimeric intron sequence <400> SEQUENCE: 53 ggtaagttta gtctttttgt cttttatttc aggtcccgga tccggtggtg gtgcaaatca 60 aagaactgct cctcagtgga tgttgccttt acttctaggc ctgtacggaa gtgttacttc 120 tgctctaaaa gctgcggaat tgtacccgc 149 <210> SEQ ID NO 54 <211> LENGTH: 126 <212> TYPE: DNA <213> ORGANISM: Homo sapiens <400> SEQUENCE: 54 agtctgcggt gggcagcgga ggagtcgtgt cgtgcctgag agcgcagctg tgctcctggg 60 caccgcgcag tccgcccccg cggctcctgg ccagaccacc cctaggaccc cctgccccaa 120 gtcgca 126 <210> SEQ ID NO 55 <211> LENGTH: 121 <212> TYPE: DNA <213> ORGANISM: Human betaherpesvirus 5 <400> SEQUENCE: 55 tcagatcgcc tggagaggcc atccacgctg ttttgacctc catagtggac accgggaccg 60 atccagcctc cgcggccggg aacggtgcat tggaacgcgg attccccgtg ccaagagtga 120 c 121 <210> SEQ ID NO 56 <211> LENGTH: 512 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Made in Lab - adenovirus derived enhancer element <400> SEQUENCE: 56 ctcactctct tccgcatcgc tgtctgcgag ggccagctgt tgggctcgcg gttgaggaca 60 aactcttcgc ggtctttcca gtactcttgg atcggaaacc cgtcggcctc cgaacggtac 120 tccgccaccg agggacctga gcgagtccgc atcgaccgga tcggaaaacc tctcgagaaa 180 ggcgtctaac cagtcacagt cgcaaggtag gctgagcacc gtggcgggcg gcagcgggtg 240 gcggtcgggg ttgtttctgg cggaggtgct gctgatgatg taattaaagt aggcggtctt 300 gagacggcgg atggtcgagg tgaggtgtgg caggcttgag atccagctgt tggggtgagt 360 actccctctc aaaagcgggc attacttctg cgctaagatt gtcagtttcc aaaaacgagg 420 aggatttgat attcacctgg cccgatctgg ccatacactt gagtgacaat gacatccact 480 ttgcctttct ctccacaggt gtccactccc ag 512 <210> SEQ ID NO 57 <211> LENGTH: 956 <212> TYPE: DNA <213> ORGANISM: Homo sapiens <400> SEQUENCE: 57 ctttttcgca acgggtttgc cgccagaaca caggtaagtg ccgtgtgtgg ttcccgcggg 60 cctggcctct ttacgggtta tggcccttgc gtgccttgaa ttacttccac ctggctccag 120 tacgtgattc ttgatcccga gctggagcca ggggcgggcc ttgcgcttta ggagcccctt 180 cgcctcgtgc ttgagttgag gcctggcctg ggcgctgggg ccgccgcgtg cgaatctggt 240 ggcaccttcg cgcctgtctc gctgctttcg ataagtctct agccatttaa aatttttgat 300 gacgtgctgc gacgcttttt ttctggcaag atagtcttgt aaatgcgggc caggatctgc 360 acactggtat ttcggttttt gggcccgcgg ccggcgacgg ggcccgtgcg tcccagcgca 420 catgttcggc gaggcggggc ctgcgagcgc ggccaccgag aatcggacgg gggtagtctc 480 aagctggccg gcctgctctg gtgcctggcc tcgcgccgcc gtgtatcgcc ccgccctggg 540 cggcaaggct ggcccggtcg gcaccagttg cgtgagcgga aagatggccg cttcccggcc 600 ctgctccagg gggctcaaaa tggaggacgc ggcgctcggg agagcgggcg ggtgagtcac 660 ccacacaaag gaaaagggcc tttccgtcct cagccgtcgc ttcatgtgac tccacggagt 720 accgggcgcc gtccaggcac ctcgattagt tctggagctt ttggagtacg tcgtctttag 780 gttgggggga ggggttttat gcgatggagt ttccccacac tgagtgggtg gagactgaag 840 ttaggccagc ttggcacttg atgtaattct ccttggaatt tggccttttt gagtttggat 900 cttggttcat tctcaagcct cagacagtgg ttcaaagttt ttttcttcca tttcag 956 <210> SEQ ID NO 58 <211> LENGTH: 939 <212> TYPE: DNA <213> ORGANISM: Homo sapiens <400> SEQUENCE: 58 gtaagtgccg tgtgtggttc ccgcgggcct ggcctcttta cgggttatgg cccttgcgtg 60 ccttgaatta cttccacctg gctgcagtac gtgattcttg atcccgagct tcgggttgga 120 agtgggtggg agagttcgag gccttgcgct taaggagccc cttcgcctcg tgcttgagtt 180 gaggcctggc ctgggcgctg gggccgccgc gtgcgaatct ggtggcacct tcgcgcctgt 240 ctcgctgctt tcgataagtc tctagccatt taaaattttt gatgacctgc tgcgacgctt 300 tttttctggc aagatagtct tgtaaatgcg ggccaagatc tgcacactgg tatttcggtt 360 tttggggccg cgggcggcga cggggcccgt gcgtcccagc gcacatgttc ggcgaggcgg 420 ggcctgcgag cgcggccacc gagaatcgga cgggggtagt ctcaagctgg ccggcctgct 480 ctggtgcctg gcctcgcgcc gccgtgtatc gccccgccct gggcggcaag gctggcccgg 540

tcggcaccag ttgcgtgagc ggaaagatgg ccgcttcccg gccctgctgc agggagctca 600 aaatggagga cgcggcgctc gggagagcgg gcgggtgagt cacccacaca aaggaaaagg 660 gcctttccgt cctcagccgt cgcttcatgt gactccacgg agtaccgggc gccgtccagg 720 cacctcgatt agttctcgag cttttggagt acgtcgtctt taggttgggg ggaggggttt 780 tatgcgatgg agtttcccca cactgagtgg gtggagactg aagttaggcc agcttggcac 840 ttgatgtaat tctccttgga atttgccctt tttgagtttg gatcttggtt cattctcaag 900 cctcagacag tggttcaaag tttttttctt ccatttcag 939 <210> SEQ ID NO 59 <211> LENGTH: 83 <212> TYPE: DNA <213> ORGANISM: Homo sapiens <400> SEQUENCE: 59 tcagaagccc cgggctcgtc agtcaaaccg gttctctgtt tgcactcggc agcacgggca 60 ggcaagtggt ccctaggttc ggg 83 <210> SEQ ID NO 60 <211> LENGTH: 476 <212> TYPE: DNA <213> ORGANISM: Homo sapiens <400> SEQUENCE: 60 gtgagtctat gggacccttg atgttttctt tccccttctt ttctatggtt aagttcatgt 60 cataggaagg ggagaagtaa cagggtacac atattgacca aatcagggta attttgcatt 120 tgtaatttta aaaaatgctt tcttctttta atatactttt ttgtttatct tatttctaat 180 actttcccta atctctttct ttcagggcaa taatgataca atgtatcatg cctctttgca 240 ccattctaaa gaataacagt gataatttct gggttaaggc aatagcaata tttctgcata 300 taaatatttc tgcatataaa ttgtaactga tgtaagaggt ttcatattgc taatagcagc 360 tacaatccag ctaccattct gcttttattt tatggttggg ataaggctgg attattctga 420 gtccaagcta ggcccttttg ctaatcatgt tcatacctct tatcttcctc ccacag 476 <210> SEQ ID NO 61 <211> LENGTH: 196 <212> TYPE: DNA <213> ORGANISM: simian virus 40 <400> SEQUENCE: 61 tctagaggat ccggtactcg aggaactgaa aaaccagaaa gttaactggt aagtttagtc 60 tttttgtctt ttatttcagg tcccggatcc ggtggtggtg caaatcaaag aactgctcct 120 cagtggatgt tgcctttact tctaggcctg tacggaagtg ttacttctgc tctaaaagct 180 gcggaattgt acccgc 196 <210> SEQ ID NO 62 <211> LENGTH: 589 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Made in Lab - mutated woodchuck hepatitis regulatory element <400> SEQUENCE: 62 aatcaacctc tggattacaa aatttgtgaa agattgactg gtattcttaa ctatgttgct 60 ccttttacgc tatgtggata cgctgcttta atgcctttgt atcatgctat tgcttcccgt 120 atggctttca ttttctcctc cttgtataaa tcctggttgc tgtctcttta tgaggagttg 180 tggcccgttg tcaggcaacg tggcgtggtg tgcactgtgt ttgctgacgc aacccccact 240 ggttggggca ttgccaccac ctgtcagctc ctttccggga ctttcgcttt ccccctccct 300 attgccacgg cggaactcat cgccgcctgc cttgcccgct gctggacagg ggctcggctg 360 ttgggcactg acaattccgt ggtgttgtcg gggaaatcat cgtcctttcc ttggctgctc 420 gcctgtgttg ccacctggat tctgcgcggg acgtccttct gctacgtccc ttcggccctc 480 aatccagcgg accttccttc ccgcggcctg ctgccggctc tgcggcctct tccgcgtctt 540 cgccttcgcc ctcagacgag tcggatctcc ctttgggccg cctccccgc 589 <210> SEQ ID NO 63 <211> LENGTH: 588 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Made in Lab - mutated woodchuck hepatitis regulatory element <400> SEQUENCE: 63 tcaacctctg gattacaaaa tttgtgaaag attgactggt attcttaact atgttgctcc 60 ttttacgcta tgtggatacg ctgctttaat gcctttgtat catgctattg cttcccgtat 120 ggctttcatt ttctcctcct tgtataaatc ctggttgctg tctctttatg aggagttgtg 180 gcccgttgtc aggcaacgtg gcgtggtgtg cactgtgttt gctgacgcaa cccccactgg 240 ttggggcatt gccaccacct gtcagctcct ttccgggact ttcgctttcc ccctccctat 300 tgccacggcg gaactcatcg ccgcctgcct tgcccgctgc tggacagggg ctcggctgtt 360 gggcactgac aattccgtgg tgttgtcggg gaaatcatcg tcctttcctt ggctgctcgc 420 ctgtgttgcc acctggattc tgcgcgggac gtccttctgc tacgtccctt cggccctcaa 480 tccagcggac cttccttccc gcggcctgct gccggctctg cggcctcttc cgcgtcttcg 540 ccttcgccct cagacgagtc ggatctccct ttgggccgcc tccccgca 588 <210> SEQ ID NO 64 <211> LENGTH: 755 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Made in Lab - mutated woodchuck hepatitis regulatory element <400> SEQUENCE: 64 ttcctgttaa tcaacctctg gattacaaaa tttgtgaaag attgactggt attcttaact 60 atgttgctcc ttttacgcta tgtggatacg ctgctttaat gcctttgtat catgctattg 120 cttcccgtat ggctttcatt ttctcctcct tgtataaatc ctggttgctg tctctttatg 180 aggagttgtg gcccgttgtc aggcaacgtg gcgtggtgtg cactgtgttt gctgacgcaa 240 cccccactgg ttggggcatt gccaccacct gtcagctcct ttccgggact ttcgctttcc 300 ccctccctat tgccacggcg gaactcatcg ccgcctgcct tgcccgctgc tggacagggg 360 ctcggctgtt gggcactgac aattccgtgg tgttgtcggg gaagctgacg tcctttccgc 420 ggctgctcgc ctgtgttgcc acctggattc tgcgcgggac gtccttctgc tacgtccctt 480 cggccctcaa tccagcggac cttccttccc gcggcctgct gccggctctg cggcctcttc 540 cgcctcttcg ccttcgccct cagacgagtc ggatctccct ttgggccgcc tccccgccca 600 tgtatctttt tcacctgtgc cttgtttttg cctgtgttcc gcgtcctact tttcaagcct 660 ccaagctgtg ccttgggcgg ctttggggca tggacataga tccctataaa gaatttggtt 720 catcttatca gttgttgaat tttcttcctt tggac 755 <210> SEQ ID NO 65 <211> LENGTH: 12 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: CAAX motif <400> SEQUENCE: 65 tgtgtgataa tg 12 <210> SEQ ID NO 66 <211> LENGTH: 810 <212> TYPE: DNA <213> ORGANISM: Homo sapiens <400> SEQUENCE: 66 ctgttctcat cacatcatat caaggttata taccatcaat attgccacag atgttactta 60 gccttttaat atttctctaa tttagtgtat atgcaatgat agttctctga tttctgagat 120 tgagtttctc atgtgtaatg attatttaga gtttctcttt catctgttca aatttttgtc 180 tagttttatt ttttactgat ttgtaagact tctttttata atctgcatat tacaattctc 240 tttactgggg tgttgcaaat attttctgtc attctatggc ctgacttttc ttaatggttt 300 tttaatttta aaaataagtc ttaatattca tgcaatctaa ttaacaatct tttctttgtg 360 gttaggactt tgagtcataa gaaatttttc tctacactga agtcatgatg gcatgcttct 420 atattatttt ctaaaagatt taaagttttg ccttctccat ttagacttat aattcactgg 480 aatttttttg tgtgtatggt atgacatatg ggttcccttt tattttttac atataaatat 540 atttccctgt ttttctaaaa aagaaaaaga tcatcatttt cccattgtaa aatgccatat 600 ttttttcata ggtcacttac atatatcaat gggtctgttt ctgagctcta ctctatttta 660 tcagcctcac tgtctatccc cacacatctc atgctttgct ctaaatcttg atatttagtg 720 gaacattctt tcccattttg ttctacaaga atatttttgt tattgtcttt gggctttcta 780 tatacatttt gaaatgaggt tgacaagtta 810 <210> SEQ ID NO 67 <211> LENGTH: 726 <212> TYPE: DNA <213> ORGANISM: Hepatitis B virus <400> SEQUENCE: 67 ataacaggcc tattgattgg aaagtttgtc aacgaattgt gggtcttttg gggtttgctg 60 ccccttttac gcaatgtgga tatcctgctt taatgccttt atatgcatgt atacaagcaa 120 aacaggcttt tactttctcg ccaacttaca aggcctttct cagtaaacag tatatgaccc 180 tttaccccgt tgctcggcaa cggcctggtc tgtgccaagt gtttgctgac gcaaccccca 240 ctggttgggg cttggccata ggccatcagc gcatgcgtgg aacctttgtg tctcctctgc 300 cgatccatac tgcggaactc ctagccgctt gttttgctcg cagcaggtct ggagcaaacc 360 tcatcgggac cgacaattct gtcgtactct cccgcaagta tacatcgttt ccatggctgc 420 taggctgtgc tgccaactgg atcctgcgcg ggacgtcctt tgtttacgtc ccgtcggcgc 480 tgaatcccgc ggacgacccc tcccggggcc gcttggggct ctaccgcccg cttctccgtc 540 tgccgtaccg tccgaccacg gggcgcacct ctctttacgc ggactccccg tctgtgcctt 600 ctcatctgcc ggaccgtgtg cacttcgctt cacctctgca cgtcgcatgg aggccaccgt 660 gaacgcccac cggaacctgc ccaaggtctt gcataagagg actcttggac tttcagcaat 720 gtcatc 726 <210> SEQ ID NO 68 <211> LENGTH: 755

<212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Made in Lab - HepB derived enhancer element <400> SEQUENCE: 68 ttcctgtaaa caggcctatt gattggaaag tttgtcaacg aattgtgggt cttttggggt 60 ttgctgcccc ttttacgcaa tgtggatatc ctgctttaat gcctttatat gcatgtatac 120 aagcaaaaca ggcttttact ttctcgccaa cttacaaggc ctttctcagt aaacagtata 180 tgacccttta ccccgttgct cggcaacggc ctggtctgtg ccaagtgttt gctgacgcaa 240 cccccactgg ttggggcttg gccataggcc atcagcgcat gcgtggaacc tttgtgtctc 300 ctctgccgat ccatactgcg gaactcctag ccgcttgttt tgctcgcagc tggactggag 360 caaacctcat cgggaccgac aattctgtcg tactctcccg caagcactca ccgtttccgc 420 ggctgctcgc ctgtgttgcc acctggattc tgcgcgggac gtccttctgc tacgtccctt 480 cggccctcaa tccagcggac cttccttccc gcggcctgct gccggctctg cggcctcttc 540 cgcctcttcg ccttcgccct cagacgagtc ggatctccct ttgggccgcc tccccgccca 600 tgtatctttt tcacctgtgc cttgtttttg cctgtgttcc gcgtcctact tttcaagcct 660 ccaagctgtg ccttgggcgg ctttggggca tggacataga tccctataaa gaatttggtt 720 catcttatca gttgttgaat tttcttcctt tggac 755 <210> SEQ ID NO 69 <211> LENGTH: 94 <212> TYPE: DNA <213> ORGANISM: Homo sapiens <400> SEQUENCE: 69 gctggagcct cggtagccgt tcctcctgcc cgctgggcct cccaacgggc cctcctcccc 60 tccttgcacc ggcccttcct ggtctttgaa taaa 94 <210> SEQ ID NO 70 <211> LENGTH: 596 <212> TYPE: DNA <213> ORGANISM: Woodchuck hepatitis virus <400> SEQUENCE: 70 attcgagcat cttaccgcca tttattccca tatttgttct gtttttcttg atttgggtat 60 acatttaaat gttaataaaa caaaatggtg gggcaatcat ttacattttt agggatatgt 120 aattactagt tcaggtgtat tgccacaaga caaacatgtt aagaaacttt cccgttattt 180 acgctctgtt cctgttaatc aacctctgga ttacaaaatt tgtgaaagat tgactgatat 240 tcttaactat gttgctcctt ttacgctgtg tggatatgct gctttaatgc ctctgtatca 300 tgctattgct tcccgtacgg ctttcgtttt ctcctccttg tataaatcct ggttgctgtc 360 tctttatgag gagttgtggc ccgttgtccg tcaacgtggc gtggtgtgct ctgtgtttgc 420 tgacgcaacc cccactggct ggggcattgc caccacctgt caactccttt ctgggacttt 480 cgctttcccc ctcccgatcg ccacggcaga actcatcgcc gcctgccttg cccgctgctg 540 gacaggggct aggttgctgg gcactgataa ttccgtggtg ttgtcgggga agggcc 596 <210> SEQ ID NO 71 <211> LENGTH: 387 <212> TYPE: DNA <213> ORGANISM: Oryctolagus cuniculus <400> SEQUENCE: 71 tggctaataa aggaaattta ttttcattgc aatagtgtgt tggaattttt tgtgtctctc 60 actcggaaga acatatggga gggcaaatca tttaaaacat cagaatgagt atttggttta 120 gagtttggca acatatgccc atatgctggc tgccatgaac aaaggttggc tataaagagg 180 tcatcagtat atgaaacagc cccctgctgt ccattcctta ttccatagaa aagccttgac 240 ttgaggttag atttttttta tattttgttt tgtgttattt ttttctttaa catccctaaa 300 attttcctta catgttttac tagccagatt tttcctcctc tcctgactac tcccagtcat 360 agctgtccct cttctcttat ggagatc 387 <210> SEQ ID NO 72 <211> LENGTH: 251 <212> TYPE: DNA <213> ORGANISM: Bos taurus <400> SEQUENCE: 72 ttgccagcca tctgttgttt gcccctcccc cgtgccttcc ttgaccctgg aaggtgccac 60 tcccactgtc ctttcctaat aaaatgagga aattgcatcg cattgtctga gtaggtgtca 120 ttctattctg gggggtgggg tggggcagga cagcaagggg gaggattggg aatacaatag 180 caggcatgct ggggatgcgg tgggctctat gggtacccag gtgctgaaga attgacccgg 240 ttcctcctgg g 251 <210> SEQ ID NO 73 <211> LENGTH: 251 <212> TYPE: DNA <213> ORGANISM: Bos taurus <400> SEQUENCE: 73 ttgccagcca tctgttgttt gcccctcccc cgtgccttcc ttgaccctgg aaggtgccac 60 tcccactgtc ctttcctaat aaaatgagga aattgcatcg cattgtctga gtaggtgtca 120 ttctattctg gggggtgggg tggggcagga cagcaagggg gaggattggg aagacaatag 180 caggcatgct ggggatgcgg tgggctctat gggtacccag gtgctgaaga attgacccgg 240 ttcctcctgg g 251 <210> SEQ ID NO 74 <211> LENGTH: 225 <212> TYPE: DNA <213> ORGANISM: Bos taurus <400> SEQUENCE: 74 ctgtgccttc tagttgccag ccatctgttg tttgcccctc ccccgtgcct tccttgaccc 60 tggaaggtgc cactcccact gtcctttcct aataaaatga ggaaattgca tcgcattgtc 120 tgagtaggtg tcattctatt ctggggggtg gggtggggca ggacagcaag ggggaggatt 180 gggaagacaa tagcaggcat gctggggatg cggtgggctc tatgg 225 <210> SEQ ID NO 75 <211> LENGTH: 202 <212> TYPE: DNA <213> ORGANISM: Homo sapiens <400> SEQUENCE: 75 ctgcccgggt ggcatccctg tgacccctcc ccagtgcctc tcctggccct ggaagttgcc 60 actccagtgc ccaccagcct tgtcctaata aaattaagtt gcatcatttt gtctgactag 120 gtgtccttct ataatattat ggggtggagg ggggtggtat ggagcaaggg gcccaagttg 180 ggaagaaacc tgtagggcct gc 202 <210> SEQ ID NO 76 <211> LENGTH: 735 <212> TYPE: PRT <213> ORGANISM: Adeno-associated virus 2 <400> SEQUENCE: 76 Met Ala Ala Asp Gly Tyr Leu Pro Asp Trp Leu Glu Asp Thr Leu Ser 1 5 10 15 Glu Gly Ile Arg Gln Trp Trp Lys Leu Lys Pro Gly Pro Pro Pro Pro 20 25 30 Lys Pro Ala Glu Arg His Lys Asp Asp Ser Arg Gly Leu Val Leu Pro 35 40 45 Gly Tyr Lys Tyr Leu Gly Pro Phe Asn Gly Leu Asp Lys Gly Glu Pro 50 55 60 Val Asn Glu Ala Asp Ala Ala Ala Leu Glu His Asp Lys Ala Tyr Asp 65 70 75 80 Arg Gln Leu Asp Ser Gly Asp Asn Pro Tyr Leu Lys Tyr Asn His Ala 85 90 95 Asp Ala Glu Phe Gln Glu Arg Leu Lys Glu Asp Thr Ser Phe Gly Gly 100 105 110 Asn Leu Gly Arg Ala Val Phe Gln Ala Lys Lys Arg Val Leu Glu Pro 115 120 125 Leu Gly Leu Val Glu Glu Pro Val Lys Thr Ala Pro Gly Lys Lys Arg 130 135 140 Pro Val Glu His Ser Pro Val Glu Pro Asp Ser Ser Ser Gly Thr Gly 145 150 155 160 Lys Ala Gly Gln Gln Pro Ala Arg Lys Arg Leu Asn Phe Gly Gln Thr 165 170 175 Gly Asp Ala Asp Ser Val Pro Asp Pro Gln Pro Leu Gly Gln Pro Pro 180 185 190 Ala Ala Pro Ser Gly Leu Gly Thr Asn Thr Met Ala Thr Gly Ser Gly 195 200 205 Ala Pro Met Ala Asp Asn Asn Glu Gly Ala Asp Gly Val Gly Asn Ser 210 215 220 Ser Gly Asn Trp His Cys Asp Ser Thr Trp Met Gly Asp Arg Val Ile 225 230 235 240 Thr Thr Ser Thr Arg Thr Trp Ala Leu Pro Thr Tyr Asn Asn His Leu 245 250 255 Tyr Lys Gln Ile Ser Ser Gln Ser Gly Ala Ser Asn Asp Asn His Tyr 260 265 270 Phe Gly Tyr Ser Thr Pro Trp Gly Tyr Phe Asp Phe Asn Arg Phe His 275 280 285 Cys His Phe Ser Pro Arg Asp Trp Gln Arg Leu Ile Asn Asn Asn Trp 290 295 300 Gly Phe Arg Pro Lys Arg Leu Asn Phe Lys Leu Phe Asn Ile Gln Val 305 310 315 320 Lys Glu Val Thr Gln Asn Asp Gly Thr Thr Thr Ile Ala Asn Asn Leu 325 330 335 Thr Ser Thr Val Gln Val Phe Thr Asp Ser Glu Tyr Gln Leu Pro Tyr 340 345 350 Val Leu Gly Ser Ala His Gln Gly Cys Leu Pro Pro Phe Pro Ala Asp 355 360 365 Val Phe Met Val Pro Gln Tyr Gly Tyr Leu Thr Leu Asn Asn Gly Ser 370 375 380 Gln Ala Val Gly Arg Ser Ser Phe Tyr Cys Leu Glu Tyr Phe Pro Ser 385 390 395 400 Gln Met Leu Arg Thr Gly Asn Asn Phe Thr Phe Ser Tyr Thr Phe Glu 405 410 415 Asp Val Pro Phe His Ser Ser Tyr Ala His Ser Gln Ser Leu Asp Arg

420 425 430 Leu Met Asn Pro Leu Ile Asp Gln Tyr Leu Tyr Tyr Leu Ser Arg Thr 435 440 445 Asn Thr Pro Ser Gly Thr Thr Thr Gln Ser Arg Leu Gln Phe Ser Gln 450 455 460 Ala Gly Ala Ser Asp Ile Arg Asp Gln Ser Arg Asn Trp Leu Pro Gly 465 470 475 480 Pro Cys Tyr Arg Gln Gln Arg Val Ser Lys Thr Ser Ala Asp Asn Asn 485 490 495 Asn Ser Glu Tyr Ser Trp Thr Gly Ala Thr Lys Tyr His Leu Asn Gly 500 505 510 Arg Asp Ser Leu Val Asn Pro Gly Pro Ala Met Ala Ser His Lys Asp 515 520 525 Asp Glu Glu Lys Phe Phe Pro Gln Ser Gly Val Leu Ile Phe Gly Lys 530 535 540 Gln Gly Ser Glu Lys Thr Asn Val Asp Ile Glu Lys Val Met Ile Thr 545 550 555 560 Asp Glu Glu Glu Ile Arg Thr Thr Asn Pro Val Ala Thr Glu Gln Tyr 565 570 575 Gly Ser Val Ser Thr Asn Leu Gln Arg Gly Asn Arg Gln Ala Ala Thr 580 585 590 Ala Asp Val Asn Thr Gln Gly Val Leu Pro Gly Met Val Trp Gln Asp 595 600 605 Arg Asp Val Tyr Leu Gln Gly Pro Ile Trp Ala Lys Ile Pro His Thr 610 615 620 Asp Gly His Phe His Pro Ser Pro Leu Met Gly Gly Phe Gly Leu Lys 625 630 635 640 His Pro Pro Pro Gln Ile Leu Ile Lys Asn Thr Pro Val Pro Ala Asn 645 650 655 Pro Ser Thr Thr Phe Ser Ala Ala Lys Phe Ala Ser Phe Ile Thr Gln 660 665 670 Tyr Ser Thr Gly Gln Val Ser Val Glu Ile Glu Trp Glu Leu Gln Lys 675 680 685 Glu Asn Ser Lys Arg Trp Asn Pro Glu Ile Gln Tyr Thr Ser Asn Tyr 690 695 700 Asn Lys Ser Val Asn Val Asp Phe Thr Val Asp Thr Asn Gly Val Tyr 705 710 715 720 Ser Glu Pro Arg Pro Ile Gly Thr Arg Tyr Leu Thr Arg Asn Leu 725 730 735 <210> SEQ ID NO 77 <211> LENGTH: 736 <212> TYPE: PRT <213> ORGANISM: Adeno-associated virus 9 <400> SEQUENCE: 77 Met Ala Ala Asp Gly Tyr Leu Pro Asp Trp Leu Glu Asp Asn Leu Ser 1 5 10 15 Glu Gly Ile Arg Glu Trp Trp Ala Leu Lys Pro Gly Ala Pro Gln Pro 20 25 30 Lys Ala Asn Gln Gln His Gln Asp Asn Ala Arg Gly Leu Val Leu Pro 35 40 45 Gly Tyr Lys Tyr Leu Gly Pro Gly Asn Gly Leu Asp Lys Gly Glu Pro 50 55 60 Val Asn Ala Ala Asp Ala Ala Ala Leu Glu His Asp Lys Ala Tyr Asp 65 70 75 80 Gln Gln Leu Lys Ala Gly Asp Asn Pro Tyr Leu Lys Tyr Asn His Ala 85 90 95 Asp Ala Glu Phe Gln Glu Arg Leu Lys Glu Asp Thr Ser Phe Gly Gly 100 105 110 Asn Leu Gly Arg Ala Val Phe Gln Ala Lys Lys Arg Leu Leu Glu Pro 115 120 125 Leu Gly Leu Val Glu Glu Ala Ala Lys Thr Ala Pro Gly Lys Lys Arg 130 135 140 Pro Val Glu Gln Ser Pro Gln Glu Pro Asp Ser Ser Ala Gly Ile Gly 145 150 155 160 Lys Ser Gly Ala Gln Pro Ala Lys Lys Arg Leu Asn Phe Gly Gln Thr 165 170 175 Gly Asp Thr Glu Ser Val Pro Asp Pro Gln Pro Ile Gly Glu Pro Pro 180 185 190 Ala Ala Pro Ser Gly Val Gly Ser Leu Thr Met Ala Ser Gly Gly Gly 195 200 205 Ala Pro Val Ala Asp Asn Asn Glu Gly Ala Asp Gly Val Gly Ser Ser 210 215 220 Ser Gly Asn Trp His Cys Asp Ser Gln Trp Leu Gly Asp Arg Val Ile 225 230 235 240 Thr Thr Ser Thr Arg Thr Trp Ala Leu Pro Thr Tyr Asn Asn His Leu 245 250 255 Tyr Lys Gln Ile Ser Asn Ser Thr Ser Gly Gly Ser Ser Asn Asp Asn 260 265 270 Ala Tyr Phe Gly Tyr Ser Thr Pro Trp Gly Tyr Phe Asp Phe Asn Arg 275 280 285 Phe His Cys His Phe Ser Pro Arg Asp Trp Gln Arg Leu Ile Asn Asn 290 295 300 Asn Trp Gly Phe Arg Pro Lys Arg Leu Asn Phe Lys Leu Phe Asn Ile 305 310 315 320 Gln Val Lys Glu Val Thr Asp Asn Asn Gly Val Lys Thr Ile Ala Asn 325 330 335 Asn Leu Thr Ser Thr Val Gln Val Phe Thr Asp Ser Asp Tyr Gln Leu 340 345 350 Pro Tyr Val Leu Gly Ser Ala His Glu Gly Cys Leu Pro Pro Phe Pro 355 360 365 Ala Asp Val Phe Met Ile Pro Gln Tyr Gly Tyr Leu Thr Leu Asn Asp 370 375 380 Gly Ser Gln Ala Val Gly Arg Ser Ser Phe Tyr Cys Leu Glu Tyr Phe 385 390 395 400 Pro Ser Gln Met Leu Arg Thr Gly Asn Asn Phe Gln Phe Ser Tyr Glu 405 410 415 Phe Glu Asn Val Pro Phe His Ser Ser Tyr Ala His Ser Gln Ser Leu 420 425 430 Asp Arg Leu Met Asn Pro Leu Ile Asp Gln Tyr Leu Tyr Tyr Leu Ser 435 440 445 Lys Thr Ile Asn Gly Ser Gly Gln Asn Gln Gln Thr Leu Lys Phe Ser 450 455 460 Val Ala Gly Pro Ser Asn Met Ala Val Gln Gly Arg Asn Tyr Ile Pro 465 470 475 480 Gly Pro Ser Tyr Arg Gln Gln Arg Val Ser Thr Thr Val Thr Gln Asn 485 490 495 Asn Asn Ser Glu Phe Ala Trp Pro Gly Ala Ser Ser Trp Ala Leu Asn 500 505 510 Gly Arg Asn Ser Leu Met Asn Pro Gly Pro Ala Met Ala Ser His Lys 515 520 525 Glu Gly Glu Asp Arg Phe Phe Pro Leu Ser Gly Ser Leu Ile Phe Gly 530 535 540 Lys Gln Gly Thr Gly Arg Asp Asn Val Asp Ala Asp Lys Val Met Ile 545 550 555 560 Thr Asn Glu Glu Glu Ile Lys Thr Thr Asn Pro Val Ala Thr Glu Ser 565 570 575 Tyr Gly Gln Val Ala Thr Asn His Gln Ser Ala Gln Ala Gln Ala Gln 580 585 590 Thr Gly Trp Val Gln Asn Gln Gly Ile Leu Pro Gly Met Val Trp Gln 595 600 605 Asp Arg Asp Val Tyr Leu Gln Gly Pro Ile Trp Ala Lys Ile Pro His 610 615 620 Thr Asp Gly Asn Phe His Pro Ser Pro Leu Met Gly Gly Phe Gly Met 625 630 635 640 Lys His Pro Pro Pro Gln Ile Leu Ile Lys Asn Thr Pro Val Pro Ala 645 650 655 Asp Pro Pro Thr Ala Phe Asn Lys Asp Lys Leu Asn Ser Phe Ile Thr 660 665 670 Gln Tyr Ser Thr Gly Gln Val Ser Val Glu Ile Glu Trp Glu Leu Gln 675 680 685 Lys Glu Asn Ser Lys Arg Trp Asn Pro Glu Ile Gln Tyr Thr Ser Asn 690 695 700 Tyr Tyr Lys Ser Asn Asn Val Glu Phe Ala Val Asn Thr Glu Gly Val 705 710 715 720 Tyr Ser Glu Pro Arg Pro Ile Gly Thr Arg Tyr Leu Thr Arg Asn Leu 725 730 735 <210> SEQ ID NO 78 <211> LENGTH: 736 <212> TYPE: PRT <213> ORGANISM: Adeno-associated virus 6 <400> SEQUENCE: 78 Met Ala Ala Asp Gly Tyr Leu Pro Asp Trp Leu Glu Asp Asn Leu Ser 1 5 10 15 Glu Gly Ile Arg Glu Trp Trp Asp Leu Lys Pro Gly Ala Pro Lys Pro 20 25 30 Lys Ala Asn Gln Gln Lys Gln Asp Asp Gly Arg Gly Leu Val Leu Pro 35 40 45 Gly Tyr Lys Tyr Leu Gly Pro Phe Asn Gly Leu Asp Lys Gly Glu Pro 50 55 60 Val Asn Ala Ala Asp Ala Ala Ala Leu Glu His Asp Lys Ala Tyr Asp 65 70 75 80 Gln Gln Leu Lys Ala Gly Asp Asn Pro Tyr Leu Arg Tyr Asn His Ala 85 90 95 Asp Ala Glu Phe Gln Glu Arg Leu Gln Glu Asp Thr Ser Phe Gly Gly 100 105 110 Asn Leu Gly Arg Ala Val Phe Gln Ala Lys Lys Arg Val Leu Glu Pro 115 120 125 Phe Gly Leu Val Glu Glu Gly Ala Lys Thr Ala Pro Gly Lys Lys Arg 130 135 140 Pro Val Glu Gln Ser Pro Gln Glu Pro Asp Ser Ser Ser Gly Ile Gly 145 150 155 160 Lys Thr Gly Gln Gln Pro Ala Lys Lys Arg Leu Asn Phe Gly Gln Thr 165 170 175 Gly Asp Ser Glu Ser Val Pro Asp Pro Gln Pro Leu Gly Glu Pro Pro 180 185 190 Ala Thr Pro Ala Ala Val Gly Pro Thr Thr Met Ala Ser Gly Gly Gly 195 200 205

Ala Pro Met Ala Asp Asn Asn Glu Gly Ala Asp Gly Val Gly Asn Ala 210 215 220 Ser Gly Asn Trp His Cys Asp Ser Thr Trp Leu Gly Asp Arg Val Ile 225 230 235 240 Thr Thr Ser Thr Arg Thr Trp Ala Leu Pro Thr Tyr Asn Asn His Leu 245 250 255 Tyr Lys Gln Ile Ser Ser Ala Ser Thr Gly Ala Ser Asn Asp Asn His 260 265 270 Tyr Phe Gly Tyr Ser Thr Pro Trp Gly Tyr Phe Asp Phe Asn Arg Phe 275 280 285 His Cys His Phe Ser Pro Arg Asp Trp Gln Arg Leu Ile Asn Asn Asn 290 295 300 Trp Gly Phe Arg Pro Lys Arg Leu Asn Phe Lys Leu Phe Asn Ile Gln 305 310 315 320 Val Lys Glu Val Thr Thr Asn Asp Gly Val Thr Thr Ile Ala Asn Asn 325 330 335 Leu Thr Ser Thr Val Gln Val Phe Ser Asp Ser Glu Tyr Gln Leu Pro 340 345 350 Tyr Val Leu Gly Ser Ala His Gln Gly Cys Leu Pro Pro Phe Pro Ala 355 360 365 Asp Val Phe Met Ile Pro Gln Tyr Gly Tyr Leu Thr Leu Asn Asn Gly 370 375 380 Ser Gln Ala Val Gly Arg Ser Ser Phe Tyr Cys Leu Glu Tyr Phe Pro 385 390 395 400 Ser Gln Met Leu Arg Thr Gly Asn Asn Phe Thr Phe Ser Tyr Thr Phe 405 410 415 Glu Asp Val Pro Phe His Ser Ser Tyr Ala His Ser Gln Ser Leu Asp 420 425 430 Arg Leu Met Asn Pro Leu Ile Asp Gln Tyr Leu Tyr Tyr Leu Asn Arg 435 440 445 Thr Gln Asn Gln Ser Gly Ser Ala Gln Asn Lys Asp Leu Leu Phe Ser 450 455 460 Arg Gly Ser Pro Ala Gly Met Ser Val Gln Pro Lys Asn Trp Leu Pro 465 470 475 480 Gly Pro Cys Tyr Arg Gln Gln Arg Val Ser Lys Thr Lys Thr Asp Asn 485 490 495 Asn Asn Ser Asn Phe Thr Trp Thr Gly Ala Ser Lys Tyr Asn Leu Asn 500 505 510 Gly Arg Glu Ser Ile Ile Asn Pro Gly Thr Ala Met Ala Ser His Lys 515 520 525 Asp Asp Lys Asp Lys Phe Phe Pro Met Ser Gly Val Met Ile Phe Gly 530 535 540 Lys Glu Ser Ala Gly Ala Ser Asn Thr Ala Leu Asp Asn Val Met Ile 545 550 555 560 Thr Asp Glu Glu Glu Ile Lys Ala Thr Asn Pro Val Ala Thr Glu Arg 565 570 575 Phe Gly Thr Val Ala Val Asn Leu Gln Ser Ser Ser Thr Asp Pro Ala 580 585 590 Thr Gly Asp Val His Val Met Gly Ala Leu Pro Gly Met Val Trp Gln 595 600 605 Asp Arg Asp Val Tyr Leu Gln Gly Pro Ile Trp Ala Lys Ile Pro His 610 615 620 Thr Asp Gly His Phe His Pro Ser Pro Leu Met Gly Gly Phe Gly Leu 625 630 635 640 Lys His Pro Pro Pro Gln Ile Leu Ile Lys Asn Thr Pro Val Pro Ala 645 650 655 Asn Pro Pro Ala Glu Phe Ser Ala Thr Lys Phe Ala Ser Phe Ile Thr 660 665 670 Gln Tyr Ser Thr Gly Gln Val Ser Val Glu Ile Glu Trp Glu Leu Gln 675 680 685 Lys Glu Asn Ser Lys Arg Trp Asn Pro Glu Val Gln Tyr Thr Ser Asn 690 695 700 Tyr Ala Lys Ser Ala Asn Val Asp Phe Thr Val Asp Asn Asn Gly Leu 705 710 715 720 Tyr Thr Glu Pro Arg Pro Ile Gly Thr Arg Tyr Leu Thr Arg Pro Leu 725 730 735 <210> SEQ ID NO 79 <211> LENGTH: 738 <212> TYPE: PRT <213> ORGANISM: Non-human primate Adeno-associated virus <400> SEQUENCE: 79 Met Ala Ala Asp Gly Tyr Leu Pro Asp Trp Leu Glu Asp Asn Leu Ser 1 5 10 15 Glu Gly Ile Arg Glu Trp Trp Asp Leu Lys Pro Gly Ala Pro Lys Pro 20 25 30 Lys Ala Asn Gln Gln Lys Gln Asp Asp Gly Arg Gly Leu Val Leu Pro 35 40 45 Gly Tyr Lys Tyr Leu Gly Pro Phe Asn Gly Leu Asp Lys Gly Glu Pro 50 55 60 Val Asn Ala Ala Asp Ala Ala Ala Leu Glu His Asp Lys Ala Tyr Asp 65 70 75 80 Gln Gln Leu Lys Ala Gly Asp Asn Pro Tyr Leu Arg Tyr Asn His Ala 85 90 95 Asp Ala Glu Phe Gln Glu Arg Leu Gln Glu Asp Thr Ser Phe Gly Gly 100 105 110 Asn Leu Gly Arg Ala Val Phe Gln Ala Lys Lys Arg Val Leu Glu Pro 115 120 125 Leu Gly Leu Val Glu Glu Gly Ala Lys Thr Ala Pro Gly Lys Lys Arg 130 135 140 Pro Val Glu Pro Ser Pro Gln Arg Ser Pro Asp Ser Ser Thr Gly Ile 145 150 155 160 Gly Lys Lys Gly Gln Gln Pro Ala Lys Lys Arg Leu Asn Phe Gly Gln 165 170 175 Thr Gly Asp Ser Glu Ser Val Pro Asp Pro Gln Pro Ile Gly Glu Pro 180 185 190 Pro Ala Gly Pro Ser Gly Leu Gly Ser Gly Thr Met Ala Ala Gly Gly 195 200 205 Gly Ala Pro Met Ala Asp Asn Asn Glu Gly Ala Asp Gly Val Gly Ser 210 215 220 Ser Ser Gly Asn Trp His Cys Asp Ser Thr Trp Leu Gly Asp Arg Val 225 230 235 240 Ile Thr Thr Ser Thr Arg Thr Trp Ala Leu Pro Thr Tyr Asn Asn His 245 250 255 Leu Tyr Lys Gln Ile Ser Asn Gly Thr Ser Gly Gly Ser Thr Asn Asp 260 265 270 Asn Thr Tyr Phe Gly Tyr Ser Thr Pro Trp Gly Tyr Phe Asp Phe Asn 275 280 285 Arg Phe His Cys His Phe Ser Pro Arg Asp Trp Gln Arg Leu Ile Asn 290 295 300 Asn Asn Trp Gly Phe Arg Pro Lys Arg Leu Asn Phe Lys Leu Phe Asn 305 310 315 320 Ile Gln Val Lys Glu Val Thr Gln Asn Glu Gly Thr Lys Thr Ile Ala 325 330 335 Asn Asn Leu Thr Ser Thr Ile Gln Val Phe Thr Asp Ser Glu Tyr Gln 340 345 350 Leu Pro Tyr Val Leu Gly Ser Ala His Gln Gly Cys Leu Pro Pro Phe 355 360 365 Pro Ala Asp Val Phe Met Ile Pro Gln Tyr Gly Tyr Leu Thr Leu Asn 370 375 380 Asn Gly Ser Gln Ala Val Gly Arg Ser Ser Phe Tyr Cys Leu Glu Tyr 385 390 395 400 Phe Pro Ser Gln Met Leu Arg Thr Gly Asn Asn Phe Glu Phe Ser Tyr 405 410 415 Gln Phe Glu Asp Val Pro Phe His Ser Ser Tyr Ala His Ser Gln Ser 420 425 430 Leu Asp Arg Leu Met Asn Pro Leu Ile Asp Gln Tyr Leu Tyr Tyr Leu 435 440 445 Ser Arg Thr Gln Ser Thr Gly Gly Thr Ala Gly Thr Gln Gln Leu Leu 450 455 460 Phe Ser Gln Ala Gly Pro Asn Asn Met Ser Ala Gln Ala Lys Asn Trp 465 470 475 480 Leu Pro Gly Pro Cys Tyr Arg Gln Gln Arg Val Ser Thr Thr Leu Ser 485 490 495 Gln Asn Asn Asn Ser Asn Phe Ala Trp Thr Gly Ala Thr Lys Tyr His 500 505 510 Leu Asn Gly Arg Asp Ser Leu Val Asn Pro Gly Val Ala Met Ala Thr 515 520 525 His Lys Asp Asp Glu Glu Arg Phe Phe Pro Ser Ser Gly Val Leu Met 530 535 540 Phe Gly Lys Gln Gly Ala Gly Lys Asp Asn Val Asp Tyr Ser Ser Val 545 550 555 560 Met Leu Thr Ser Glu Glu Glu Ile Lys Thr Thr Asn Pro Val Ala Thr 565 570 575 Glu Gln Tyr Gly Val Val Ala Asp Asn Leu Gln Gln Gln Asn Ala Ala 580 585 590 Pro Ile Val Gly Ala Val Asn Ser Gln Gly Ala Leu Pro Gly Met Val 595 600 605 Trp Gln Asn Arg Asp Val Tyr Leu Gln Gly Pro Ile Trp Ala Lys Ile 610 615 620 Pro His Thr Asp Gly Asn Phe His Pro Ser Pro Leu Met Gly Gly Phe 625 630 635 640 Gly Leu Lys His Pro Pro Pro Gln Ile Leu Ile Lys Asn Thr Pro Val 645 650 655 Pro Ala Asp Pro Pro Thr Thr Phe Ser Gln Ala Lys Leu Ala Ser Phe 660 665 670 Ile Thr Gln Tyr Ser Thr Gly Gln Val Ser Val Glu Ile Glu Trp Glu 675 680 685 Leu Gln Lys Glu Asn Ser Lys Arg Trp Asn Pro Glu Ile Gln Tyr Thr 690 695 700 Ser Asn Tyr Tyr Lys Ser Thr Asn Val Asp Phe Ala Val Asn Thr Asp 705 710 715 720 Gly Thr Tyr Ser Glu Pro Arg Pro Ile Gly Thr Arg Tyr Leu Thr Arg 725 730 735 Asn Leu <210> SEQ ID NO 80 <211> LENGTH: 2217

<212> TYPE: DNA <213> ORGANISM: Non-human primate adeno-associated virus <400> SEQUENCE: 80 atggctgccg atggttatct tccagattgg ctcgaggaca acctctctga gggcattcgc 60 gagtggtggg acctgaaacc tggagccccg aaacccaaag ccaaccagca aaagcaggac 120 aacggccggg gtctggtgct tcctggctac aagtacctcg gacccttcaa cggactcgac 180 aagggggagc ccgtcaacgc ggcggacgca gcggccctcg agcacgacaa ggcctacgac 240 cagcagctcc aagcgggtga caatccgtac ctgcggtata atcacgccga cgccgagttt 300 caggagcgtc tgcaagaaga tacgtctttt gggggcaacc tcgggcgcgc agtcttccag 360 gccaaaaagc gggttctcga acctctgggc ctggttgaat cgccggttaa gacggctcct 420 ggaaagaaga gaccggtaga gccatcaccc cagcgctctc cagactcctc tacgggcatc 480 ggcaagaaag gccagcagcc cgcaaaaaag agactcaatt ttgggcagac tggcgactca 540 gagtcagtcc ccgaccctca accaatcgga gaaccaccag caggcccctc tggtctggga 600 tctggtacaa tggctgcagg cggtggcgct ccaatggcag acaataacga aggcgccgac 660 ggagtgggta gttcctcagg aaattggcat tgcgattcca catggctggg cgacagagtc 720 atcaccacca gcacccgcac ctgggccctg cccacctaca acaaccacct ctacaagcaa 780 atctccaacg ggacctcggg aggaagcacc aacgacaaca cctacttcgg ctacagcacc 840 ccctgggggt attttgactt caacagattc cactgccact tttcaccacg tgactggcag 900 cgactcatca acaacaactg gggattccgg cccaagaggc tcaacttcaa gctcttcaac 960 atccaagtca aggaggtcac gcagaatgaa ggcaccaaga ccatcgccaa taaccttacc 1020 agcacgattc aggtctttac ggactcggaa taccagctcc cgtacgtgct cggctcggcg 1080 caccagggct gcctgcctcc gttcccggcg gacgtcttca tgattcctca gtacgggtac 1140 ctgactctga acaatggcag tcaggctgtg ggccggtcgt ccttctactg cctggagtac 1200 tttccttctc aaatgctgag aacgggcaac aactttgaat tcagctacaa cttcgaggac 1260 gtgcccttcc acagcagcta cgcgcacagc cagagcctgg accggctgat gaaccctctc 1320 atcgaccagt acttgtacta cctgtcccgg actcaaagca cgggcggtac tgcaggaact 1380 cagcagttgc tattttctca ggccgggcct aacaacatgt cggctcaggc caagaactgg 1440 ctacccggtc cctgctaccg gcagcaacgc gtctccacga cactgtcgca gaacaacaac 1500 agcaactttg cctggacggg tgccaccaag tatcatctga atggcagaga ctctctggtg 1560 aatcctggcg ttgccatggc tacccacaag gacgacgaag agcgattttt tccatccagc 1620 ggagtcttaa tgtttgggaa acagggagct ggaaaagaca acgtggacta tagcagcgtg 1680 atgctaacca gcgaggaaga aataaagacc accaacccag tggccacaga acagtacggc 1740 gtggtggccg ataacctgca acagcaaaac gccgctccta ttgtaggggc cgtcaatagt 1800 caaggagcct tacctggcat ggtgtggcag aaccgggacg tgtacctgca gggtcccatc 1860 tgggccaaga ttcctcatac ggacggcaac tttcatccct cgccgctgat gggaggcttt 1920 ggactgaagc atccgcctcc tcagatcctg attaaaaaca cacctgttcc cgcggatcct 1980 ccgaccacct tcaatcaggc caagctggct tctttcatca cgcagtacag taccggccag 2040 gtcagcgtgg agatcgagtg ggagctgcag aaggagaaca gcaaacgctg gaacccagag 2100 attcagtaca cttccaacta ctacaaatct acaaatgtgg actttgctgt caatactgag 2160 ggtacttatt ccgagcctcg ccccattggc acccgttacc tcacccgtaa tctgtaa 2217 <210> SEQ ID NO 81 <211> LENGTH: 535 <212> TYPE: PRT <213> ORGANISM: Non-human primate adeno-associated virus <400> SEQUENCE: 81 Met Ala Ala Gly Gly Gly Ala Pro Met Ala Asp Asn Asn Glu Gly Ala 1 5 10 15 Asp Gly Val Gly Ser Ser Ser Gly Asn Trp His Cys Asp Ser Thr Trp 20 25 30 Leu Gly Asp Arg Val Ile Thr Thr Ser Thr Arg Thr Trp Ala Leu Pro 35 40 45 Thr Tyr Asn Asn His Leu Tyr Lys Gln Ile Ser Asn Gly Thr Ser Gly 50 55 60 Gly Ser Thr Asn Asp Asn Thr Tyr Phe Gly Tyr Ser Thr Pro Trp Gly 65 70 75 80 Tyr Phe Asp Phe Asn Arg Phe His Cys His Phe Ser Pro Arg Asp Trp 85 90 95 Gln Arg Leu Ile Asn Asn Asn Trp Gly Phe Arg Pro Lys Arg Leu Asn 100 105 110 Phe Lys Leu Phe Asn Ile Gln Val Lys Glu Val Thr Gln Asn Glu Gly 115 120 125 Thr Lys Thr Ile Ala Asn Asn Leu Thr Ser Thr Ile Gln Val Phe Thr 130 135 140 Asp Ser Glu Tyr Gln Leu Pro Tyr Val Leu Gly Ser Ala His Gln Gly 145 150 155 160 Cys Leu Pro Pro Phe Pro Ala Asp Val Phe Met Ile Pro Gln Tyr Gly 165 170 175 Tyr Leu Thr Leu Asn Asn Gly Ser Gln Ala Val Gly Arg Ser Ser Phe 180 185 190 Tyr Cys Leu Glu Tyr Phe Pro Ser Gln Met Leu Arg Thr Gly Asn Asn 195 200 205 Phe Glu Phe Ser Tyr Asn Phe Glu Asp Val Pro Phe His Ser Ser Tyr 210 215 220 Ala His Ser Gln Ser Leu Asp Arg Leu Met Asn Pro Leu Ile Asp Gln 225 230 235 240 Tyr Leu Tyr Tyr Leu Ser Arg Thr Gln Ser Thr Gly Gly Thr Ala Gly 245 250 255 Thr Gln Gln Leu Leu Phe Ser Gln Ala Gly Pro Asn Asn Met Ser Ala 260 265 270 Gln Ala Lys Asn Trp Leu Pro Gly Pro Cys Tyr Arg Gln Gln Arg Val 275 280 285 Ser Thr Thr Leu Ser Gln Asn Asn Asn Ser Asn Phe Ala Trp Thr Gly 290 295 300 Ala Thr Lys Tyr His Leu Asn Gly Arg Asp Ser Leu Val Asn Pro Gly 305 310 315 320 Val Ala Met Ala Thr His Lys Asp Asp Glu Glu Arg Phe Phe Pro Ser 325 330 335 Ser Gly Val Leu Met Phe Gly Lys Gln Gly Ala Gly Lys Asp Asn Val 340 345 350 Asp Tyr Ser Ser Val Met Leu Thr Ser Glu Glu Glu Ile Lys Thr Thr 355 360 365 Asn Pro Val Ala Thr Glu Gln Tyr Gly Val Val Ala Asp Asn Leu Gln 370 375 380 Gln Gln Asn Ala Ala Pro Ile Val Gly Ala Val Asn Ser Gln Gly Ala 385 390 395 400 Leu Pro Gly Met Val Trp Gln Asn Arg Asp Val Tyr Leu Gln Gly Pro 405 410 415 Ile Trp Ala Lys Ile Pro His Thr Asp Gly Asn Phe His Pro Ser Pro 420 425 430 Leu Met Gly Gly Phe Gly Leu Lys His Pro Pro Pro Gln Ile Leu Ile 435 440 445 Lys Asn Thr Pro Val Pro Ala Asp Pro Pro Thr Thr Phe Asn Gln Ala 450 455 460 Lys Leu Ala Ser Phe Ile Thr Gln Tyr Ser Thr Gly Gln Val Ser Val 465 470 475 480 Glu Ile Glu Trp Glu Leu Gln Lys Glu Asn Ser Lys Arg Trp Asn Pro 485 490 495 Glu Ile Gln Tyr Thr Ser Asn Tyr Tyr Lys Ser Thr Asn Val Asp Phe 500 505 510 Ala Val Asn Thr Glu Gly Thr Tyr Ser Glu Pro Arg Pro Ile Gly Thr 515 520 525 Arg Tyr Leu Thr Arg Asn Leu 530 535 <210> SEQ ID NO 82 <211> LENGTH: 398 <212> TYPE: PRT <213> ORGANISM: Non-human primate adeno-associated virus <400> SEQUENCE: 82 Ser Thr Ile Gln Val Phe Thr Asp Ser Glu Tyr Gln Leu Pro Tyr Val 1 5 10 15 Leu Gly Ser Ala His Gln Gly Cys Leu Pro Pro Phe Pro Ala Asp Val 20 25 30 Phe Met Ile Pro Gln Tyr Gly Tyr Leu Thr Leu Asn Asn Gly Ser Gln 35 40 45 Ala Val Gly Arg Ser Ser Phe Tyr Cys Leu Glu Tyr Phe Pro Ser Gln 50 55 60 Met Leu Arg Thr Gly Asn Asn Phe Glu Phe Ser Tyr Asn Phe Glu Asp 65 70 75 80 Val Pro Phe His Ser Ser Tyr Ala His Ser Gln Ser Leu Asp Arg Leu 85 90 95 Met Asn Pro Leu Ile Asp Gln Tyr Leu Tyr Tyr Leu Ser Arg Thr Gln 100 105 110 Ser Thr Gly Gly Thr Ala Gly Thr Gln Gln Leu Leu Phe Ser Gln Ala 115 120 125 Gly Pro Asn Asn Met Ser Ala Gln Ala Lys Asn Trp Leu Pro Gly Pro 130 135 140 Cys Tyr Arg Gln Gln Arg Val Ser Thr Thr Leu Ser Gln Asn Asn Asn 145 150 155 160 Ser Asn Phe Ala Trp Thr Gly Ala Thr Lys Tyr His Leu Asn Gly Arg 165 170 175 Asp Ser Leu Val Asn Pro Gly Val Ala Met Ala Thr His Lys Asp Asp 180 185 190 Glu Glu Arg Phe Phe Pro Ser Ser Gly Val Leu Met Phe Gly Lys Gln 195 200 205 Gly Ala Gly Lys Asp Asn Val Asp Tyr Ser Ser Val Met Leu Thr Ser 210 215 220 Glu Glu Glu Ile Lys Thr Thr Asn Pro Val Ala Thr Glu Gln Tyr Gly 225 230 235 240 Val Val Ala Asp Asn Leu Gln Gln Gln Asn Ala Ala Pro Ile Val Gly 245 250 255 Ala Val Asn Ser Gln Gly Ala Leu Pro Gly Met Val Trp Gln Asn Arg 260 265 270 Asp Val Tyr Leu Gln Gly Pro Ile Trp Ala Lys Ile Pro His Thr Asp 275 280 285

Gly Asn Phe His Pro Ser Pro Leu Met Gly Gly Phe Gly Leu Lys His 290 295 300 Pro Pro Pro Gln Ile Leu Ile Lys Asn Thr Pro Val Pro Ala Asp Pro 305 310 315 320 Pro Thr Thr Phe Asn Gln Ala Lys Leu Ala Ser Phe Ile Thr Gln Tyr 325 330 335 Ser Thr Gly Gln Val Ser Val Glu Ile Glu Trp Glu Leu Gln Lys Glu 340 345 350 Asn Ser Lys Arg Trp Asn Pro Glu Ile Gln Tyr Thr Ser Asn Tyr Tyr 355 360 365 Lys Ser Thr Asn Val Asp Phe Ala Val Asn Thr Glu Gly Thr Tyr Ser 370 375 380 Glu Pro Arg Pro Ile Gly Thr Arg Tyr Leu Thr Arg Asn Leu 385 390 395 <210> SEQ ID NO 83 <211> LENGTH: 332 <212> TYPE: PRT <213> ORGANISM: Non-human primate adeno-associated virus <400> SEQUENCE: 83 Arg Thr Gly Asn Asn Phe Glu Phe Ser Tyr Asn Phe Glu Asp Val Pro 1 5 10 15 Phe His Ser Ser Tyr Ala His Ser Gln Ser Leu Asp Arg Leu Met Asn 20 25 30 Pro Leu Ile Asp Gln Tyr Leu Tyr Tyr Leu Ser Arg Thr Gln Ser Thr 35 40 45 Gly Gly Thr Ala Gly Thr Gln Gln Leu Leu Phe Ser Gln Ala Gly Pro 50 55 60 Asn Asn Met Ser Ala Gln Ala Lys Asn Trp Leu Pro Gly Pro Cys Tyr 65 70 75 80 Arg Gln Gln Arg Val Ser Thr Thr Leu Ser Gln Asn Asn Asn Ser Asn 85 90 95 Phe Ala Trp Thr Gly Ala Thr Lys Tyr His Leu Asn Gly Arg Asp Ser 100 105 110 Leu Val Asn Pro Gly Val Ala Met Ala Thr His Lys Asp Asp Glu Glu 115 120 125 Arg Phe Phe Pro Ser Ser Gly Val Leu Met Phe Gly Lys Gln Gly Ala 130 135 140 Gly Lys Asp Asn Val Asp Tyr Ser Ser Val Met Leu Thr Ser Glu Glu 145 150 155 160 Glu Ile Lys Thr Thr Asn Pro Val Ala Thr Glu Gln Tyr Gly Val Val 165 170 175 Ala Asp Asn Leu Gln Gln Gln Asn Ala Ala Pro Ile Val Gly Ala Val 180 185 190 Asn Ser Gln Gly Ala Leu Pro Gly Met Val Trp Gln Asn Arg Asp Val 195 200 205 Tyr Leu Gln Gly Pro Ile Trp Ala Lys Ile Pro His Thr Asp Gly Asn 210 215 220 Phe His Pro Ser Pro Leu Met Gly Gly Phe Gly Leu Lys His Pro Pro 225 230 235 240 Pro Gln Ile Leu Ile Lys Asn Thr Pro Val Pro Ala Asp Pro Pro Thr 245 250 255 Thr Phe Asn Gln Ala Lys Leu Ala Ser Phe Ile Thr Gln Tyr Ser Thr 260 265 270 Gly Gln Val Ser Val Glu Ile Glu Trp Glu Leu Gln Lys Glu Asn Ser 275 280 285 Lys Arg Trp Asn Pro Glu Ile Gln Tyr Thr Ser Asn Tyr Tyr Lys Ser 290 295 300 Thr Asn Val Asp Phe Ala Val Asn Thr Glu Gly Thr Tyr Ser Glu Pro 305 310 315 320 Arg Pro Ile Gly Thr Arg Tyr Leu Thr Arg Asn Leu 325 330 <210> SEQ ID NO 84 <211> LENGTH: 743 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Synthetic construct - AAV9 variant <400> SEQUENCE: 84 Met Ala Ala Asp Gly Tyr Leu Pro Asp Trp Leu Glu Asp Asn Leu Ser 1 5 10 15 Glu Gly Ile Arg Glu Trp Trp Ala Leu Lys Pro Gly Ala Pro Gln Pro 20 25 30 Lys Ala Asn Gln Gln His Gln Asp Asn Ala Arg Gly Leu Val Leu Pro 35 40 45 Gly Tyr Lys Tyr Leu Gly Pro Gly Asn Gly Leu Asp Lys Gly Glu Pro 50 55 60 Val Asn Ala Ala Asp Ala Ala Ala Leu Glu His Asp Lys Ala Tyr Asp 65 70 75 80 Gln Gln Leu Lys Ala Gly Asp Asn Pro Tyr Leu Lys Tyr Asn His Ala 85 90 95 Asp Ala Glu Phe Gln Glu Arg Leu Lys Glu Asp Thr Ser Phe Gly Gly 100 105 110 Asn Leu Gly Arg Ala Val Phe Gln Ala Lys Lys Arg Leu Leu Glu Pro 115 120 125 Leu Gly Leu Val Glu Glu Ala Ala Lys Thr Ala Pro Gly Lys Lys Arg 130 135 140 Pro Val Glu Gln Ser Pro Gln Glu Pro Asp Ser Ser Ala Gly Ile Gly 145 150 155 160 Lys Ser Gly Ala Gln Pro Ala Lys Lys Arg Leu Asn Phe Gly Gln Thr 165 170 175 Gly Asp Thr Glu Ser Val Pro Asp Pro Gln Pro Ile Gly Glu Pro Pro 180 185 190 Ala Ala Pro Ser Gly Val Gly Ser Leu Thr Met Ala Ser Gly Gly Gly 195 200 205 Ala Pro Val Ala Asp Asn Asn Glu Gly Ala Asp Gly Val Gly Ser Ser 210 215 220 Ser Gly Asn Trp His Cys Asp Ser Gln Trp Leu Gly Asp Arg Val Ile 225 230 235 240 Thr Thr Ser Thr Arg Thr Trp Ala Leu Pro Thr Tyr Asn Asn His Leu 245 250 255 Tyr Lys Gln Ile Ser Asn Ser Thr Ser Gly Gly Ser Ser Asn Asp Asn 260 265 270 Ala Tyr Phe Gly Tyr Ser Thr Pro Trp Gly Tyr Phe Asp Phe Asn Arg 275 280 285 Phe His Cys His Phe Ser Pro Arg Asp Trp Gln Arg Leu Ile Asn Asn 290 295 300 Asn Trp Gly Phe Arg Pro Lys Arg Leu Asn Phe Lys Leu Phe Asn Ile 305 310 315 320 Gln Val Lys Glu Val Thr Asp Asn Asn Gly Val Lys Thr Ile Ala Asn 325 330 335 Asn Leu Thr Ser Thr Val Gln Val Phe Thr Asp Ser Asp Tyr Gln Leu 340 345 350 Pro Tyr Val Leu Gly Ser Ala His Glu Gly Cys Leu Pro Pro Phe Pro 355 360 365 Ala Asp Val Phe Met Ile Pro Gln Tyr Gly Tyr Leu Thr Leu Asn Asp 370 375 380 Gly Ser Gln Ala Val Gly Arg Ser Ser Phe Tyr Cys Leu Glu Tyr Phe 385 390 395 400 Pro Ser Gln Met Leu Arg Thr Gly Asn Asn Phe Gln Phe Ser Tyr Glu 405 410 415 Phe Glu Asn Val Pro Phe His Ser Ser Tyr Ala His Ser Gln Ser Leu 420 425 430 Asp Arg Leu Met Asn Pro Leu Ile Asp Gln Tyr Leu Tyr Tyr Leu Ser 435 440 445 Arg Thr Ile Asn Gly Ser Gly Gln Asn Gln Gln Thr Leu Lys Phe Ser 450 455 460 Val Ala Gly Pro Ser Asn Met Ala Val Gln Gly Arg Asn Tyr Ile Pro 465 470 475 480 Gly Pro Ser Tyr Arg Gln Gln Arg Val Ser Thr Thr Val Thr Gln Asn 485 490 495 Asn Asn Ser Glu Phe Ala Trp Pro Gly Ala Ser Ser Trp Ala Leu Asn 500 505 510 Gly Arg Asn Ser Leu Met Asn Pro Gly Pro Ala Met Ala Ser His Lys 515 520 525 Glu Gly Glu Asp Arg Phe Phe Pro Leu Ser Gly Ser Leu Ile Phe Gly 530 535 540 Lys Gln Gly Thr Gly Arg Asp Asn Val Asp Ala Asp Lys Val Met Ile 545 550 555 560 Thr Asn Glu Glu Glu Ile Lys Thr Thr Asn Pro Val Ala Thr Glu Ser 565 570 575 Tyr Gly Gln Val Ala Thr Asn His Gln Ser Ala Gln Thr Leu Ala Val 580 585 590 Pro Phe Lys Ala Gln Ala Gln Thr Gly Trp Val Gln Asn Gln Gly Ile 595 600 605 Leu Pro Gly Met Val Trp Gln Asp Arg Asp Val Tyr Leu Gln Gly Pro 610 615 620 Ile Trp Ala Lys Ile Pro His Thr Asp Gly Asn Phe His Pro Ser Pro 625 630 635 640 Leu Met Gly Gly Phe Gly Met Lys His Pro Pro Pro Gln Ile Leu Ile 645 650 655 Lys Asn Thr Pro Val Pro Ala Asp Pro Pro Thr Ala Phe Asn Lys Asp 660 665 670 Lys Leu Asn Ser Phe Ile Thr Gln Tyr Ser Thr Gly Gln Val Ser Val 675 680 685 Glu Ile Glu Trp Glu Leu Gln Lys Glu Asn Ser Lys Arg Trp Asn Pro 690 695 700 Glu Ile Gln Tyr Thr Ser Asn Tyr Tyr Lys Ser Asn Asn Val Glu Phe 705 710 715 720 Ala Val Asn Thr Glu Gly Val Tyr Ser Glu Pro Arg Pro Ile Gly Thr 725 730 735 Arg Tyr Leu Thr Arg Asn Leu 740 <210> SEQ ID NO 85 <211> LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Peptide insert

<400> SEQUENCE: 85 Thr Leu Ala Val Pro Phe Lys 1 5 <210> SEQ ID NO 86 <211> LENGTH: 7 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Peptide insert <400> SEQUENCE: 86 Lys Phe Pro Val Ala Leu Thr 1 5 <210> SEQ ID NO 87 <211> LENGTH: 2514 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Made in Lab - codon optimized PKP2a polynucleotide <400> SEQUENCE: 87 atggctgcac ctggtgcgcc tgccgaatat ggttatataa ggacagtttt gggtcaacag 60 atacttggac aacttgattc ctcttctttg gcgctccctt cagaagcaaa gttgaaattg 120 gcaggttcat caggtagagg aggacaaact gtgaaatctc tgcggattca ggaacaagta 180 caacagactt tggctagaaa gggaagatct tccgttggca atggaaattt gcatagaacg 240 agcagcgtac ctgaatacgt atacaatctc catcttgttg aaaacgattt tgtaggaggt 300 cggtctccag ttccgaaaac atatgatatg cttaaagcag gtactacagc tacatacgaa 360 ggtagatggg gaagaggaac tgcacaatat tcatctcaaa aatctgttga agaaaggtca 420 ttgcgacatc ctctcagaag gctcgaaatt tccccggatt catcacctga aagggctcat 480 tatacacaca gtgattatca atatagccaa cgatctcaag caggtcatac acttcatcat 540 caggaaagta ggcgggcggc attgcttgta ccccctcgat atgccaggtc agaaattgta 600 ggagtttcca gagcaggtac tactagtcga caaagacact ttgacacata tcataggcaa 660 tatcaacacg gtagtgtctc agacactgtt tttgattcaa taccagcaaa tccggcattg 720 ctgacgtatc ctcgacctgg tacgtcaagg agcatgggaa atcttctgga gaaagaaaat 780 tatttgactg ctgggcttac agttggacag gtacggccat tggttcctct tcaaccagtt 840 actcagaatc gagcttccag aagctcttgg catcaatcaa gctttcattc cacaaggaca 900 ctgagagaag caggaccttc tgttgccgtt gattccagtg ggcggagagc ccaccttaca 960 gtaggtcaag cagctgccgg aggatcaggt aatttgctta cagaaaggag tacttttaca 1020 gatagccaac tcgggaatgc ggatatggaa atgacattgg agagagctgt atcaatgctg 1080 gaagcggatc atatgcttcc ttctagaatt tccgctgcgg caacttttat acagcacgaa 1140 tgttttcaaa aatccgaagc gcgaaagcgg gttaatcagc tgagaggtat tctgaaactg 1200 ttgcaacttt tgaaagtgca aaatgaagat gttcaaagag ctgtttgtgg agctcttaga 1260 aatcttgttt ttgaagataa tgataataaa ttggaagttg ctgaacttaa tggtgtacct 1320 agattgcttc aagttttgaa acaaacaaga gatttggaaa caaaaaaaca aataacagga 1380 cttttgtgga atctttcttc taatgataaa cttaaaaatt tgatgataac agaagctttg 1440 ttgacactta cagaaaatat tattatacct ttttctggat ggcctgaagg ggattatcca 1500 aaagctaatg ggttgctgga ttttgatatt ttttataatg tgacaggatg tttgaggaat 1560 atgtcctcag ctggtgctga cggtcggaaa gcaatgaggc gatgtgacgg tttgatcgat 1620 tcccttgttc attacgttag gggaacaata gctgattatc aaccagatga taaagcaaca 1680 gaaaattgtg tttgtattct tcataatctg tcttatcaat tggaagccga acttcctgaa 1740 aaatactctc aaaatatcta tattcagaat cggaacatac aaactgataa taacaaatct 1800 ataggatgtt ttggatcaag aagcagaaaa gttaaggaac aatatcaaga cgttcctatg 1860 cccgaagaaa aatcaaatcc aaagggtgta gaatggctgt ggcattctat tgttattaga 1920 atgtatttgt cactcatagc aaaatctgta cgaaattata cacaagaagc ttctttggga 1980 gcccttcaga atcttacagc aggaagtggt cctatgccta caagtgtagc gcaaacagtt 2040 gtacagaaag aatctggatt gcaacatact agaaagatgc tgcatgtagg agatccttct 2100 gttaaaaaga cagctataag cctcctgagg aacttgagtc gcaacttgtc tctccagaat 2160 gagattgcta aggaaacgct tcctgacctt gtatctatta tacctgacac ggtgccttcc 2220 acagatcttt tgattgaaac aactgcatct gcttgttata cattgaataa tatcattcaa 2280 aatagttatc agaacgcaag agatcttctg aatacaggag gtattcaaaa aataatggct 2340 atttcagcag gtgatgcata tgcttctaat aaagcgtcta aagctgcatc tgttcttttg 2400 tattctcttt gggcacatac agaacttcac catgcctaca agaaagctca attcaagaaa 2460 acagattttg ttaatagtcg cactgcaaaa gcgtatcatt cccttaagga ttaa 2514 <210> SEQ ID NO 88 <211> LENGTH: 2646 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Made in Lab - codon optimized PKP2b polynucleotide <400> SEQUENCE: 88 atggccgcac ctggagctcc agctgaatat ggatatatca ggactgtctt gggtcagcag 60 attctgggcc aactggattc ttcaagtctg gccctcccga gtgaggcaaa actgaaactc 120 gcaggatcta gtggaagggg cggacagaca gtgaagtcac tcaggattca ggagcaggtc 180 caacagacac tggcaagaaa agggaggtcc agcgtcggca atggtaactt gcatagaacc 240 tcttcagtgc ctgagtacgt gtacaacctg cacctggtgg aaaacgattt tgtgggcggc 300 agatccccgg tccctaaaac ttatgacatg ctgaaagctg gcacgacagc tacatatgaa 360 ggtagatggg gccggggcac cgcacaatat agttctcaga agtccgtgga agaaagatct 420 cttaggcacc cacttcggcg actggagata agtccagaca gcagccccga aagggcgcat 480 tatacacatt ctgactacca atacagccaa agatctcagg ctggccacac tctgcatcat 540 caggaaagta gaagggccgc ccttctcgtc cccccaagat acgcacggtc agaaatcgtg 600 ggagtgagca gagcaggtac cacctctcga cagaggcatt tcgacacata ccaccgacaa 660 taccaacatg gatcagtgtc agatactgtt tttgactcca taccagcaaa tccagcactc 720 ctgacatatc ctagaccggg gactagtcgc tccatgggga atctgctcga aaaagaaaac 780 tatctcaccg caggtctgac tgtggggcag gtaaggccgt tggtgcccct tcagcctgta 840 acgcagaata gggcttccag gtcatcctgg caccagagta gcttccactc cacaaggact 900 ctgagagagg caggccctag tgttgcagtt gatagttccg gtcgcagggc ccatcttaca 960 gttggtcaag ccgctgcagg gggtagcggt aatctgctga ccgaaagaag cacattcacg 1020 gattcccagc tcggaaatgc agacatggag atgacacttg aacgagccgt gagcatgctg 1080 gaagctgacc atatgctccc ttctagaatc tccgctgcgg ccactttcat ccagcacgag 1140 tgctttcaga aatccgaagc taggaaacgc gtgaaccagc tgaggggcat cctgaagctg 1200 ctgcagctgc ttaaggtgca gaatgaggat gtccaacgcg cagtgtgcgg tgctctgagg 1260 aacctcgtgt ttgaagataa cgataataag ttggaagtcg cagaacttaa cggggtacct 1320 cgactgctcc aggtgttgaa acagacacgg gacctggaaa cgaaaaaaca aattaccgac 1380 cacactgtga atctcagaag tcggaatggg tggcctgggg cagtagctca tgcctgtaac 1440 ccttctacat tgggtggcca aggcgggagg attaccagat caggggtacg ggatcaacct 1500 gatcagcacg ggctcctgtg gaacttgtcc tctaatgaca aactgaaaaa cctgatgata 1560 accgaggctc tgctgaccct gacagaaaac attatcatcc ccttctccgg atggccagaa 1620 ggagactatc ctaaagctaa cggcttgctg gacttcgata tcttttataa tgtcacaggg 1680 tgccttagaa atatgagtag cgccggtgcc gatggaagga aggcaatgcg ccggtgtgat 1740 ggtcttatcg attccctggt acattacgtg aggggcacca ttgccgacta ccaaccagac 1800 gataaagcaa ccgagaattg cgtgtgcatc ctgcacaatt tgagctacca actcgaagct 1860 gaactgcctg agaaatattc ccaaaatatt tatatccaga atcggaatat ccagaccgat 1920 aataacaaga gcataggatg ctttggttct agaagccgca aggtcaagga acagtaccag 1980 gatgtaccta tgccagagga aaaatcaaac cccaaaggag tggaatggct gtggcattcc 2040 atcgtgatca ggatgtacct gagtctgatt gctaagagcg tgaggaacta tacacaggag 2100 gcttcccttg gcgcactgca aaatctgacc gccggatctg ggccaatgcc aacaagcgtt 2160 gctcaaacag tagtgcaaaa ggaatctggc cttcagcaca ctaggaaaat gcttcatgtg 2220 ggagatcctt ctgtgaagaa gacggctatt agcctgctcc gcaacttgag cagaaacctt 2280 tctttgcaga atgagattgc gaaagagacg ctccctgacc tggtgtccat tataccagac 2340 acggtccctt ccacagatct tctgattgaa acgaccgctt ccgcatgtta caccctgaat 2400 aatattattc aaaactcata ccaaaatgct agagacctgc tgaacactgg ggggatccag 2460 aagattatgg caatttcagc cggcgatgcc tatgctagta ataaagcctc caaggccgcc 2520 agtgtattgc tgtatagtct gtgggcacat acagaactgc accacgcata taagaaggcc 2580 cagtttaaaa aaaccgattt cgtaaactct cggactgcaa aagcctacca ttcactgaaa 2640 gattga 2646 <210> SEQ ID NO 89 <211> LENGTH: 4650 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Made in Lab - polynucleotide sequence of vector genome <400> SEQUENCE: 89 gcgcgctcgc tcgctcactg aggccgcccg ggcaaagccc gggcgtcggg cgacctttgg 60 tcgcccggcc tcagtgagcg agcgagcgcg cagagaggga gtggccaact ccatcactag 120 gggttccttg tagttaatga ttaacccgcc atgctactta tctacgtact ctggagacgc 180 gtacccttca gattaaaaat aactgaggta agggcctggg taggggaggt ggtgtgagac 240 gctcctgtct ctcctctatc tgcccatcgg ccctttgggg aggaggaatg tgcccaagga 300 ctaaaaaaag gccatggagc cagaggggcg agggcaacag acctttcatg ggcaaacctt 360 ggggccctgc tgtctagcat gccccactac gggtctaggc tgcccatgta aggaggcaag 420 gcctggggac acccgagatg cctggttata attaacccag acatgtggct gccccccccc 480 ccccaacacc tgctgcctct aaaaataacc ctgtccctgg tggatcccct gcatgcgaag 540 atcttcgaac aaggctgtgg gggactgagg gcaggctgta acaggcttgg gggccagggc 600 ttatacgtgc ctgggactcc caaagtatta ctgttccatg ttcccggcga agggccagct 660 gtcccccgcc agctagactc agcacttagt ttaggaacca gtgagcaagt cagcccttgg 720 ggcagcccat acaaggccat ggggctgggc aagctgcacg cctgggtccg gggtgggcac 780

ggtgcccggg caacgagctg aaagctcatc tgctctcagg ggcccctccc tggggacagc 840 ccctcctggc tagtcacacc ctgtaggctc ctctatataa cccaggggca caggggctgc 900 cctcattcta ccaccacctc cacagcacag acagacactc aggagccagc cagggtaagt 960 ttagtctttt tgtcttttat ttcaggtccc ggatccggtg gtggtgcaaa tcaaagaact 1020 gctcctcagt ggatgttgcc tttacttcta ggcctgtacg gaagtgttac ttctgctcta 1080 aaagctgcgg aattgtaccc gcgccaccat ggcagccccc ggcgccccag ctgagtacgg 1140 ctacatccgg accgtcctgg gccagcagat cctgggacaa ctggacagct ccagcctggc 1200 gctgccctcc gaggccaagc tgaagctggc ggggagcagc ggccgcggcg gccagacagt 1260 caagagcctg cggatccagg agcaggtgca gcagaccctc gcccggaagg gccgcagctc 1320 cgtgggcaac ggaaatcttc accgaaccag cagtgttcct gagtatgtct acaacctaca 1380 cttggttgaa aatgattttg ttggaggccg ttcccctgtt cctaaaacct atgacatgct 1440 aaaggctggc acaactgcca cttatgaagg tcgctgggga agaggaacag cacagtacag 1500 ctcccagaag tccgtggaag aaaggtcctt gaggcatcct ctgaggagac tggagatttc 1560 tcctgacagc agcccggaga gggctcacta cacgcacagc gattaccagt acagccagag 1620 aagccaggct gggcacaccc tgcaccacca agaaagcagg cgggccgccc tcctagtgcc 1680 accgagatat gctcgttccg agatcgtggg ggtcagccgt gctggcacca caagcaggca 1740 gcgccacttt gacacatacc acagacagta ccagcatggc tctgttagcg acaccgtttt 1800 tgacagcatc cctgccaacc cggccctgct cacgtacccc aggccaggga ccagccgcag 1860 catgggcaac ctcttggaga aggagaacta cctgacggca gggctcactg tcgggcaggt 1920 caggccgctg gtgcccctgc agcccgtcac tcagaacagg gcttccaggt cctcctggca 1980 tcagagctcc ttccacagca cccgcacgct gagggaagct gggcccagtg tcgccgtgga 2040 ttccagcggg aggagagcgc acttgactgt cggccaggcg gccgcagggg gaagtgggaa 2100 tctgctcact gagagaagca ctttcactga ctcccagctg gggaatgcag acatggagat 2160 gactctggag cgagcagtga gtatgctcga ggcagaccac atgctgccat ccaggatttc 2220 tgctgcagct actttcatac agcacgagtg cttccagaaa tctgaagctc ggaagagggt 2280 taaccagctt cgtggcatcc tcaagcttct gcagctccta aaagttcaga atgaagacgt 2340 tcagcgagct gtgtgtgggg ccttgagaaa cttagtattt gaagacaatg acaacaaatt 2400 ggaggtggct gaactaaatg gggtacctcg gctgctccag gtgctgaagc aaaccagaga 2460 cttggagact aaaaaacaaa taacaggttt gctgtggaat ttgtcatcta atgacaaact 2520 caagaatctc atgataacag aagcattgct tacgctgacg gagaatatca tcatcccctt 2580 ttctgggtgg cctgaaggag actacccaaa agcaaatggt ttgctcgatt ttgacatatt 2640 ctacaacgtc actggatgcc taagaaacat gagttctgct ggcgctgatg ggagaaaagc 2700 gatgagaaga tgtgacggac tcattgactc actggtccat tatgtcagag gaaccattgc 2760 agattaccag ccagatgaca aggccacgga gaattgtgtg tgcattcttc ataacctctc 2820 ctaccagctg gaggcagagc tcccagagaa atattcccag aatatctata ttcaaaaccg 2880 gaatatccag actgacaaca acaaaagtat tggatgtttt ggcagtcgaa gcaggaaagt 2940 aaaagagcaa taccaggacg tgccgatgcc ggaggaaaag agcaacccca agggcgtgga 3000 gtggctgtgg cattccattg ttataaggat gtatctgtcc ttgatcgcca aaagtgtccg 3060 caactacaca caagaagcat ccttaggagc tctgcagaac ctcacggccg gaagtggacc 3120 aatgccgaca tcagtggctc agacagttgt ccagaaggaa agtggcctgc agcacacccg 3180 aaagatgctg catgttggtg acccaagtgt gaaaaagaca gccatctcgc tgctgaggaa 3240 tctgtcccgg aatctttctc tgcagaatga aattgccaaa gaaactctcc ctgatttggt 3300 ttccatcatt cctgacacag tcccgagtac tgaccttctc attgaaacta cagcctctgc 3360 ctgttacaca ttgaacaaca taatccaaaa cagttaccag aatgcacgcg accttctaaa 3420 caccgggggc atccagaaaa ttatggccat tagtgcaggc gatgcctatg cctccaacaa 3480 agcaagtaaa gctgcttccg tccttctgta ttctctgtgg gcacacacgg aactgcatca 3540 tgcctacaag aaggctcagt ttaagaagac agattttgtc aacagccgga ctgccaaagc 3600 ctaccactcc cttaaagact gatcaacctc tggattacaa aatttgtgaa agattgactg 3660 gtattcttaa ctatgttgct ccttttacgc tatgtggata cgctgcttta atgcctttgt 3720 atcatgctat tgcttcccgt atggctttca ttttctcctc cttgtataaa tcctggttgc 3780 tgtctcttta tgaggagttg tggcccgttg tcaggcaacg tggcgtggtg tgcactgtgt 3840 ttgctgacgc aacccccact ggttggggca ttgccaccac ctgtcagctc ctttccggga 3900 ctttcgcttt ccccctccct attgccacgg cggaactcat cgccgcctgc cttgcccgct 3960 gctggacagg ggctcggctg ttgggcactg acaattccgt ggtgttgtcg gggaaatcat 4020 cgtcctttcc ttggctgctc gcctgtgttg ccacctggat tctgcgcggg acgtccttct 4080 gctacgtccc ttcggccctc aatccagcgg accttccttc ccgcggcctg ctgccggctc 4140 tgcggcctct tccgcgtctt cgccttcgcc ctcagacgag tcggatctcc ctttgggccg 4200 cctccccgca tcattgcctg cccgggtggc atccctgtga cccctcccca gtgcctctcc 4260 tggccctgga agttgccact ccagtgccca ccagccttgt cctaataaaa ttaagttgca 4320 tcattttgtc tgactaggtg tccttctata atattatggg gtggaggggg gtggtatgga 4380 gcaaggggcc caagttggga agaaacctgt agggcctgcg ttacccaggc tggagtgcag 4440 tggcacattt ctgctcactg caacctcctc ctccctgggt tctacgtaga taagtagcat 4500 ggcgggttaa tcattaacta caaggaaccc ctagtgatgg agttggccac tccctctctg 4560 cgcgctcgct cgctcactga ggccgggcga ccaaaggtcg cccgacgccc gggctttgcc 4620 cgggcggcct cagtgagcga gcgagcgcgc 4650 <210> SEQ ID NO 90 <211> LENGTH: 4274 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Made in Lab - polynucleotide sequence of vector genome <400> SEQUENCE: 90 gcgcgctcgc tcgctcactg aggccgcccg ggcaaagccc gggcgtcggg cgacctttgg 60 tcgcccggcc tcagtgagcg agcgagcgcg cagagaggga gtggccaact ccatcactag 120 gggttccttg tagttaatga ttaacccgcc atgctactta tctacgtact ctggagacgc 180 gtctcagtcc attaggagcc agtagcctgg aagatgtctt tacccccagc atcagttcaa 240 gtggagcagc acataactct tgccctctgc cttccaagat tctggtgctg agacttatgg 300 agtgtcttgg aggttgcctt ctgcccccca accctgctcc cagctggccc tcccaggcct 360 gggttgctgg cctctgcttt atcaggattc tcaagaggga cagctggttt atgttgcatg 420 actgttccct gcatatctgc tctggtttta aatagcttat ctgagcagct ggaggaccac 480 atgggcttat atggcgtggg gtacatgttc ctgtagcctt gtccctggca cctgccaaaa 540 tagcagccaa caccccccac ccccaccgcc atccccctgc cccacccgtc ccctgtcgca 600 cattcctccc tccgcagggc tggctcacca ggccccagcc cacatgcctg cttaaagccc 660 tctccatcct ctgcctcacc cagtccccgc tgagactgag cagacgcctc caggatctgt 720 cggcaggcca ccatggcagc ccccggcgcc ccagctgagt acggctacat ccggaccgtc 780 ctgggccagc agatcctggg acaactggac agctccagcc tggcgctgcc ctccgaggcc 840 aagctgaagc tggcggggag cagcggccgc ggcggccaga cagtcaagag cctgcggatc 900 caggagcagg tgcagcagac cctcgcccgg aagggccgca gctccgtggg caacggaaat 960 cttcaccgaa ccagcagtgt tcctgagtat gtctacaacc tacacttggt tgaaaatgat 1020 tttgttggag gccgttcccc tgttcctaaa acctatgaca tgctaaaggc tggcacaact 1080 gccacttatg aaggtcgctg gggaagagga acagcacagt acagctccca gaagtccgtg 1140 gaagaaaggt ccttgaggca tcctctgagg agactggaga tttctcctga cagcagcccg 1200 gagagggctc actacacgca cagcgattac cagtacagcc agagaagcca ggctgggcac 1260 accctgcacc accaagaaag caggcgggcc gccctcctag tgccaccgag atatgctcgt 1320 tccgagatcg tgggggtcag ccgtgctggc accacaagca ggcagcgcca ctttgacaca 1380 taccacagac agtaccagca tggctctgtt agcgacaccg tttttgacag catccctgcc 1440 aacccggccc tgctcacgta ccccaggcca gggaccagcc gcagcatggg caacctcttg 1500 gagaaggaga actacctgac ggcagggctc actgtcgggc aggtcaggcc gctggtgccc 1560 ctgcagcccg tcactcagaa cagggcttcc aggtcctcct ggcatcagag ctccttccac 1620 agcacccgca cgctgaggga agctgggccc agtgtcgccg tggattccag cgggaggaga 1680 gcgcacttga ctgtcggcca ggcggccgca gggggaagtg ggaatctgct cactgagaga 1740 agcactttca ctgactccca gctggggaat gcagacatgg agatgactct ggagcgagca 1800 gtgagtatgc tcgaggcaga ccacatgctg ccatccagga tttctgctgc agctactttc 1860 atacagcacg agtgcttcca gaaatctgaa gctcggaaga gggttaacca gcttcgtggc 1920 atcctcaagc ttctgcagct cctaaaagtt cagaatgaag acgttcagcg agctgtgtgt 1980 ggggccttga gaaacttagt atttgaagac aatgacaaca aattggaggt ggctgaacta 2040 aatggggtac ctcggctgct ccaggtgctg aagcaaacca gagacttgga gactaaaaaa 2100 caaataacag gtttgctgtg gaatttgtca tctaatgaca aactcaagaa tctcatgata 2160 acagaagcat tgcttacgct gacggagaat atcatcatcc ccttttctgg gtggcctgaa 2220 ggagactacc caaaagcaaa tggtttgctc gattttgaca tattctacaa cgtcactgga 2280 tgcctaagaa acatgagttc tgctggcgct gatgggagaa aagcgatgag aagatgtgac 2340 ggactcattg actcactggt ccattatgtc agaggaacca ttgcagatta ccagccagat 2400 gacaaggcca cggagaattg tgtgtgcatt cttcataacc tctcctacca gctggaggca 2460 gagctcccag agaaatattc ccagaatatc tatattcaaa accggaatat ccagactgac 2520 aacaacaaaa gtattggatg ttttggcagt cgaagcagga aagtaaaaga gcaataccag 2580 gacgtgccga tgccggagga aaagagcaac cccaagggcg tggagtggct gtggcattcc 2640 attgttataa ggatgtatct gtccttgatc gccaaaagtg tccgcaacta cacacaagaa 2700 gcatccttag gagctctgca gaacctcacg gccggaagtg gaccaatgcc gacatcagtg 2760 gctcagacag ttgtccagaa ggaaagtggc ctgcagcaca cccgaaagat gctgcatgtt 2820 ggtgacccaa gtgtgaaaaa gacagccatc tcgctgctga ggaatctgtc ccggaatctt 2880 tctctgcaga atgaaattgc caaagaaact ctccctgatt tggtttccat cattcctgac 2940 acagtcccga gtactgacct tctcattgaa actacagcct ctgcctgtta cacattgaac 3000 aacataatcc aaaacagtta ccagaatgca cgcgaccttc taaacaccgg gggcatccag 3060 aaaattatgg ccattagtgc aggcgatgcc tatgcctcca acaaagcaag taaagctgct 3120 tccgtccttc tgtattctct gtgggcacac acggaactgc atcatgccta caagaaggct 3180 cagtttaaga agacagattt tgtcaacagc cggactgcca aagcctacca ctcccttaaa 3240

gactgatcaa cctctggatt acaaaatttg tgaaagattg actggtattc ttaactatgt 3300 tgctcctttt acgctatgtg gatacgctgc tttaatgcct ttgtatcatg ctattgcttc 3360 ccgtatggct ttcattttct cctccttgta taaatcctgg ttgctgtctc tttatgagga 3420 gttgtggccc gttgtcaggc aacgtggcgt ggtgtgcact gtgtttgctg acgcaacccc 3480 cactggttgg ggcattgcca ccacctgtca gctcctttcc gggactttcg ctttccccct 3540 ccctattgcc acggcggaac tcatcgccgc ctgccttgcc cgctgctgga caggggctcg 3600 gctgttgggc actgacaatt ccgtggtgtt gtcggggaaa tcatcgtcct ttccttggct 3660 gctcgcctgt gttgccacct ggattctgcg cgggacgtcc ttctgctacg tcccttcggc 3720 cctcaatcca gcggaccttc cttcccgcgg cctgctgccg gctctgcggc ctcttccgcg 3780 tcttcgcctt cgccctcaga cgagtcggat ctccctttgg gccgcctccc cgcatcattg 3840 cctgcccggg tggcatccct gtgacccctc cccagtgcct ctcctggccc tggaagttgc 3900 cactccagtg cccaccagcc ttgtcctaat aaaattaagt tgcatcattt tgtctgacta 3960 ggtgtccttc tataatatta tggggtggag gggggtggta tggagcaagg ggcccaagtt 4020 gggaagaaac ctgtagggcc tgcgttaccc aggctggagt gcagtggcac atttctgctc 4080 actgcaacct cctcctccct gggttctacg tagataagta gcatggcggg ttaatcatta 4140 actacaagga acccctagtg atggagttgg ccactccctc tctgcgcgct cgctcgctca 4200 ctgaggccgg gcgaccaaag gtcgcccgac gcccgggctt tgcccgggcg gcctcagtga 4260 gcgagcgagc gcgc 4274 <210> SEQ ID NO 91 <211> LENGTH: 4782 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Made in Lab - polynucleotide sequence of vector genome <400> SEQUENCE: 91 gcgcgctcgc tcgctcactg aggccgcccg ggcaaagccc gggcgtcggg cgacctttgg 60 tcgcccggcc tcagtgagcg agcgagcgcg cagagaggga gtggccaact ccatcactag 120 gggttccttg tagttaatga ttaacccgcc atgctactta tctacgtact ctggagacgc 180 gtacccttca gattaaaaat aactgaggta agggcctggg taggggaggt ggtgtgagac 240 gctcctgtct ctcctctatc tgcccatcgg ccctttgggg aggaggaatg tgcccaagga 300 ctaaaaaaag gccatggagc cagaggggcg agggcaacag acctttcatg ggcaaacctt 360 ggggccctgc tgtctagcat gccccactac gggtctaggc tgcccatgta aggaggcaag 420 gcctggggac acccgagatg cctggttata attaacccag acatgtggct gccccccccc 480 ccccaacacc tgctgcctct aaaaataacc ctgtccctgg tggatcccct gcatgcgaag 540 atcttcgaac aaggctgtgg gggactgagg gcaggctgta acaggcttgg gggccagggc 600 ttatacgtgc ctgggactcc caaagtatta ctgttccatg ttcccggcga agggccagct 660 gtcccccgcc agctagactc agcacttagt ttaggaacca gtgagcaagt cagcccttgg 720 ggcagcccat acaaggccat ggggctgggc aagctgcacg cctgggtccg gggtgggcac 780 ggtgcccggg caacgagctg aaagctcatc tgctctcagg ggcccctccc tggggacagc 840 ccctcctggc tagtcacacc ctgtaggctc ctctatataa cccaggggca caggggctgc 900 cctcattcta ccaccacctc cacagcacag acagacactc aggagccagc cagggtaagt 960 ttagtctttt tgtcttttat ttcaggtccc ggatccggtg gtggtgcaaa tcaaagaact 1020 gctcctcagt ggatgttgcc tttacttcta ggcctgtacg gaagtgttac ttctgctcta 1080 aaagctgcgg aattgtaccc gcgccaccat ggcagccccc ggcgccccag ctgagtacgg 1140 ctacatccgg accgtcctgg gccagcagat cctgggacaa ctggacagct ccagcctggc 1200 gctgccctcc gaggccaagc tgaagctggc ggggagcagc ggccgcggcg gccagacagt 1260 caagagcctg cggatccagg agcaggtgca gcagaccctc gcccggaagg gccgcagctc 1320 cgtgggcaac ggaaatcttc accgaaccag cagtgttcct gagtatgtct acaacctaca 1380 cttggttgaa aatgattttg ttggaggccg ttcccctgtt cctaaaacct atgacatgct 1440 aaaggctggc acaactgcca cttatgaagg tcgctgggga agaggaacag cacagtacag 1500 ctcccagaag tccgtggaag aaaggtcctt gaggcatcct ctgaggagac tggagatttc 1560 tcctgacagc agcccggaga gggctcacta cacgcacagc gattaccagt acagccagag 1620 aagccaggct gggcacaccc tgcaccacca agaaagcagg cgggccgccc tcctagtgcc 1680 accgagatat gctcgttccg agatcgtggg ggtcagccgt gctggcacca caagcaggca 1740 gcgccacttt gacacatacc acagacagta ccagcatggc tctgttagcg acaccgtttt 1800 tgacagcatc cctgccaacc cggccctgct cacgtacccc aggccaggga ccagccgcag 1860 catgggcaac ctcttggaga aggagaacta cctgacggca gggctcactg tcgggcaggt 1920 caggccgctg gtgcccctgc agcccgtcac tcagaacagg gcttccaggt cctcctggca 1980 tcagagctcc ttccacagca cccgcacgct gagggaagct gggcccagtg tcgccgtgga 2040 ttccagcggg aggagagcgc acttgactgt cggccaggcg gccgcagggg gaagtgggaa 2100 tctgctcact gagagaagca ctttcactga ctcccagctg gggaatgcag acatggagat 2160 gactctggag cgagcagtga gtatgctcga ggcagaccac atgctgccat ccaggatttc 2220 tgctgcagct actttcatac agcacgagtg cttccagaaa tctgaagctc ggaagagggt 2280 taaccagctt cgtggcatcc tcaagcttct gcagctccta aaagttcaga atgaagacgt 2340 tcagcgagct gtgtgtgggg ccttgagaaa cttagtattt gaagacaatg acaacaaatt 2400 ggaggtggct gaactaaatg gggtacctcg gctgctccag gtgctgaagc aaaccagaga 2460 cttggagact aaaaaacaaa taacagacca tacagtcaat ttaagaagta ggaatggctg 2520 gccgggcgcg gtggctcacg cctgtaatcc cagcactttg ggaggccaag gcgggcggat 2580 cacgaggtca ggagttcgag accagcctga ccaacatggt ttgctgtgga atttgtcatc 2640 taatgacaaa ctcaagaatc tcatgataac agaagcattg cttacgctga cggagaatat 2700 catcatcccc ttttctgggt ggcctgaagg agactaccca aaagcaaatg gtttgctcga 2760 ttttgacata ttctacaacg tcactggatg cctaagaaac atgagttctg ctggcgctga 2820 tgggagaaaa gcgatgagaa gatgtgacgg actcattgac tcactggtcc attatgtcag 2880 aggaaccatt gcagattacc agccagatga caaggccacg gagaattgtg tgtgcattct 2940 tcataacctc tcctaccagc tggaggcaga gctcccagag aaatattccc agaatatcta 3000 tattcaaaac cggaatatcc agactgacaa caacaaaagt attggatgtt ttggcagtcg 3060 aagcaggaaa gtaaaagagc aataccagga cgtgccgatg ccggaggaaa agagcaaccc 3120 caagggcgtg gagtggctgt ggcattccat tgttataagg atgtatctgt ccttgatcgc 3180 caaaagtgtc cgcaactaca cacaagaagc atccttagga gctctgcaga acctcacggc 3240 cggaagtgga ccaatgccga catcagtggc tcagacagtt gtccagaagg aaagtggcct 3300 gcagcacacc cgaaagatgc tgcatgttgg tgacccaagt gtgaaaaaga cagccatctc 3360 gctgctgagg aatctgtccc ggaatctttc tctgcagaat gaaattgcca aagaaactct 3420 ccctgatttg gtttccatca ttcctgacac agtcccgagt actgaccttc tcattgaaac 3480 tacagcctct gcctgttaca cattgaacaa cataatccaa aacagttacc agaatgcacg 3540 cgaccttcta aacaccgggg gcatccagaa aattatggcc attagtgcag gcgatgccta 3600 tgcctccaac aaagcaagta aagctgcttc cgtccttctg tattctctgt gggcacacac 3660 ggaactgcat catgcctaca agaaggctca gtttaagaag acagattttg tcaacagccg 3720 gactgccaaa gcctaccact cccttaaaga ctgatcaacc tctggattac aaaatttgtg 3780 aaagattgac tggtattctt aactatgttg ctccttttac gctatgtgga tacgctgctt 3840 taatgccttt gtatcatgct attgcttccc gtatggcttt cattttctcc tccttgtata 3900 aatcctggtt gctgtctctt tatgaggagt tgtggcccgt tgtcaggcaa cgtggcgtgg 3960 tgtgcactgt gtttgctgac gcaaccccca ctggttgggg cattgccacc acctgtcagc 4020 tcctttccgg gactttcgct ttccccctcc ctattgccac ggcggaactc atcgccgcct 4080 gccttgcccg ctgctggaca ggggctcggc tgttgggcac tgacaattcc gtggtgttgt 4140 cggggaaatc atcgtccttt ccttggctgc tcgcctgtgt tgccacctgg attctgcgcg 4200 ggacgtcctt ctgctacgtc ccttcggccc tcaatccagc ggaccttcct tcccgcggcc 4260 tgctgccggc tctgcggcct cttccgcgtc ttcgccttcg ccctcagacg agtcggatct 4320 ccctttgggc cgcctccccg catcattgcc tgcccgggtg gcatccctgt gacccctccc 4380 cagtgcctct cctggccctg gaagttgcca ctccagtgcc caccagcctt gtcctaataa 4440 aattaagttg catcattttg tctgactagg tgtccttcta taatattatg gggtggaggg 4500 gggtggtatg gagcaagggg cccaagttgg gaagaaacct gtagggcctg cgttacccag 4560 gctggagtgc agtggcacat ttctgctcac tgcaacctcc tcctccctgg gttctacgta 4620 gataagtagc atggcgggtt aatcattaac tacaaggaac ccctagtgat ggagttggcc 4680 actccctctc tgcgcgctcg ctcgctcact gaggccgggc gaccaaaggt cgcccgacgc 4740 ccgggctttg cccgggcggc ctcagtgagc gagcgagcgc gc 4782 <210> SEQ ID NO 92 <211> LENGTH: 4406 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Made in Lab - polynucleotide sequence of vector genome <400> SEQUENCE: 92 gcgcgctcgc tcgctcactg aggccgcccg ggcaaagccc gggcgtcggg cgacctttgg 60 tcgcccggcc tcagtgagcg agcgagcgcg cagagaggga gtggccaact ccatcactag 120 gggttccttg tagttaatga ttaacccgcc atgctactta tctacgtact ctggagacgc 180 gtctcagtcc attaggagcc agtagcctgg aagatgtctt tacccccagc atcagttcaa 240 gtggagcagc acataactct tgccctctgc cttccaagat tctggtgctg agacttatgg 300 agtgtcttgg aggttgcctt ctgcccccca accctgctcc cagctggccc tcccaggcct 360 gggttgctgg cctctgcttt atcaggattc tcaagaggga cagctggttt atgttgcatg 420 actgttccct gcatatctgc tctggtttta aatagcttat ctgagcagct ggaggaccac 480 atgggcttat atggcgtggg gtacatgttc ctgtagcctt gtccctggca cctgccaaaa 540 tagcagccaa caccccccac ccccaccgcc atccccctgc cccacccgtc ccctgtcgca 600 cattcctccc tccgcagggc tggctcacca ggccccagcc cacatgcctg cttaaagccc 660 tctccatcct ctgcctcacc cagtccccgc tgagactgag cagacgcctc caggatctgt 720 cggcaggcca ccatggcagc ccccggcgcc ccagctgagt acggctacat ccggaccgtc 780 ctgggccagc agatcctggg acaactggac agctccagcc tggcgctgcc ctccgaggcc 840 aagctgaagc tggcggggag cagcggccgc ggcggccaga cagtcaagag cctgcggatc 900 caggagcagg tgcagcagac cctcgcccgg aagggccgca gctccgtggg caacggaaat 960

cttcaccgaa ccagcagtgt tcctgagtat gtctacaacc tacacttggt tgaaaatgat 1020 tttgttggag gccgttcccc tgttcctaaa acctatgaca tgctaaaggc tggcacaact 1080 gccacttatg aaggtcgctg gggaagagga acagcacagt acagctccca gaagtccgtg 1140 gaagaaaggt ccttgaggca tcctctgagg agactggaga tttctcctga cagcagcccg 1200 gagagggctc actacacgca cagcgattac cagtacagcc agagaagcca ggctgggcac 1260 accctgcacc accaagaaag caggcgggcc gccctcctag tgccaccgag atatgctcgt 1320 tccgagatcg tgggggtcag ccgtgctggc accacaagca ggcagcgcca ctttgacaca 1380 taccacagac agtaccagca tggctctgtt agcgacaccg tttttgacag catccctgcc 1440 aacccggccc tgctcacgta ccccaggcca gggaccagcc gcagcatggg caacctcttg 1500 gagaaggaga actacctgac ggcagggctc actgtcgggc aggtcaggcc gctggtgccc 1560 ctgcagcccg tcactcagaa cagggcttcc aggtcctcct ggcatcagag ctccttccac 1620 agcacccgca cgctgaggga agctgggccc agtgtcgccg tggattccag cgggaggaga 1680 gcgcacttga ctgtcggcca ggcggccgca gggggaagtg ggaatctgct cactgagaga 1740 agcactttca ctgactccca gctggggaat gcagacatgg agatgactct ggagcgagca 1800 gtgagtatgc tcgaggcaga ccacatgctg ccatccagga tttctgctgc agctactttc 1860 atacagcacg agtgcttcca gaaatctgaa gctcggaaga gggttaacca gcttcgtggc 1920 atcctcaagc ttctgcagct cctaaaagtt cagaatgaag acgttcagcg agctgtgtgt 1980 ggggccttga gaaacttagt atttgaagac aatgacaaca aattggaggt ggctgaacta 2040 aatggggtac ctcggctgct ccaggtgctg aagcaaacca gagacttgga gactaaaaaa 2100 caaataacag accatacagt caatttaaga agtaggaatg gctggccggg cgcggtggct 2160 cacgcctgta atcccagcac tttgggaggc caaggcgggc ggatcacgag gtcaggagtt 2220 cgagaccagc ctgaccaaca tggtttgctg tggaatttgt catctaatga caaactcaag 2280 aatctcatga taacagaagc attgcttacg ctgacggaga atatcatcat ccccttttct 2340 gggtggcctg aaggagacta cccaaaagca aatggtttgc tcgattttga catattctac 2400 aacgtcactg gatgcctaag aaacatgagt tctgctggcg ctgatgggag aaaagcgatg 2460 agaagatgtg acggactcat tgactcactg gtccattatg tcagaggaac cattgcagat 2520 taccagccag atgacaaggc cacggagaat tgtgtgtgca ttcttcataa cctctcctac 2580 cagctggagg cagagctccc agagaaatat tcccagaata tctatattca aaaccggaat 2640 atccagactg acaacaacaa aagtattgga tgttttggca gtcgaagcag gaaagtaaaa 2700 gagcaatacc aggacgtgcc gatgccggag gaaaagagca accccaaggg cgtggagtgg 2760 ctgtggcatt ccattgttat aaggatgtat ctgtccttga tcgccaaaag tgtccgcaac 2820 tacacacaag aagcatcctt aggagctctg cagaacctca cggccggaag tggaccaatg 2880 ccgacatcag tggctcagac agttgtccag aaggaaagtg gcctgcagca cacccgaaag 2940 atgctgcatg ttggtgaccc aagtgtgaaa aagacagcca tctcgctgct gaggaatctg 3000 tcccggaatc tttctctgca gaatgaaatt gccaaagaaa ctctccctga tttggtttcc 3060 atcattcctg acacagtccc gagtactgac cttctcattg aaactacagc ctctgcctgt 3120 tacacattga acaacataat ccaaaacagt taccagaatg cacgcgacct tctaaacacc 3180 gggggcatcc agaaaattat ggccattagt gcaggcgatg cctatgcctc caacaaagca 3240 agtaaagctg cttccgtcct tctgtattct ctgtgggcac acacggaact gcatcatgcc 3300 tacaagaagg ctcagtttaa gaagacagat tttgtcaaca gccggactgc caaagcctac 3360 cactccctta aagactgatc aacctctgga ttacaaaatt tgtgaaagat tgactggtat 3420 tcttaactat gttgctcctt ttacgctatg tggatacgct gctttaatgc ctttgtatca 3480 tgctattgct tcccgtatgg ctttcatttt ctcctccttg tataaatcct ggttgctgtc 3540 tctttatgag gagttgtggc ccgttgtcag gcaacgtggc gtggtgtgca ctgtgtttgc 3600 tgacgcaacc cccactggtt ggggcattgc caccacctgt cagctccttt ccgggacttt 3660 cgctttcccc ctccctattg ccacggcgga actcatcgcc gcctgccttg cccgctgctg 3720 gacaggggct cggctgttgg gcactgacaa ttccgtggtg ttgtcgggga aatcatcgtc 3780 ctttccttgg ctgctcgcct gtgttgccac ctggattctg cgcgggacgt ccttctgcta 3840 cgtcccttcg gccctcaatc cagcggacct tccttcccgc ggcctgctgc cggctctgcg 3900 gcctcttccg cgtcttcgcc ttcgccctca gacgagtcgg atctcccttt gggccgcctc 3960 cccgcatcat tgcctgcccg ggtggcatcc ctgtgacccc tccccagtgc ctctcctggc 4020 cctggaagtt gccactccag tgcccaccag ccttgtccta ataaaattaa gttgcatcat 4080 tttgtctgac taggtgtcct tctataatat tatggggtgg aggggggtgg tatggagcaa 4140 ggggcccaag ttgggaagaa acctgtaggg cctgcgttac ccaggctgga gtgcagtggc 4200 acatttctgc tcactgcaac ctcctcctcc ctgggttcta cgtagataag tagcatggcg 4260 ggttaatcat taactacaag gaacccctag tgatggagtt ggccactccc tctctgcgcg 4320 ctcgctcgct cactgaggcc gggcgaccaa aggtcgcccg acgcccgggc tttgcccggg 4380 cggcctcagt gagcgagcga gcgcgc 4406 <210> SEQ ID NO 93 <211> LENGTH: 4237 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Made in Lab - expression cassette polynucleotide <400> SEQUENCE: 93 acccttcaga ttaaaaataa ctgaggtaag ggcctgggta ggggaggtgg tgtgagacgc 60 tcctgtctct cctctatctg cccatcggcc ctttggggag gaggaatgtg cccaaggact 120 aaaaaaaggc catggagcca gaggggcgag ggcaacagac ctttcatggg caaaccttgg 180 ggccctgctg tctagcatgc cccactacgg gtctaggctg cccatgtaag gaggcaaggc 240 ctggggacac ccgagatgcc tggttataat taacccagac atgtggctgc cccccccccc 300 ccaacacctg ctgcctctaa aaataaccct gtccctggtg gatcccctgc atgcgaagat 360 cttcgaacaa ggctgtgggg gactgagggc aggctgtaac aggcttgggg gccagggctt 420 atacgtgcct gggactccca aagtattact gttccatgtt cccggcgaag ggccagctgt 480 cccccgccag ctagactcag cacttagttt aggaaccagt gagcaagtca gcccttgggg 540 cagcccatac aaggccatgg ggctgggcaa gctgcacgcc tgggtccggg gtgggcacgg 600 tgcccgggca acgagctgaa agctcatctg ctctcagggg cccctccctg gggacagccc 660 ctcctggcta gtcacaccct gtaggctcct ctatataacc caggggcaca ggggctgccc 720 tcattctacc accacctcca cagcacagac agacactcag gagccagcca gggtaagttt 780 agtctttttg tcttttattt caggtcccgg atccggtggt ggtgcaaatc aaagaactgc 840 tcctcagtgg atgttgcctt tacttctagg cctgtacgga agtgttactt ctgctctaaa 900 agctgcggaa ttgtacccgc gccaccatgg cagcccccgg cgccccagct gagtacggct 960 acatccggac cgtcctgggc cagcagatcc tgggacaact ggacagctcc agcctggcgc 1020 tgccctccga ggccaagctg aagctggcgg ggagcagcgg ccgcggcggc cagacagtca 1080 agagcctgcg gatccaggag caggtgcagc agaccctcgc ccggaagggc cgcagctccg 1140 tgggcaacgg aaatcttcac cgaaccagca gtgttcctga gtatgtctac aacctacact 1200 tggttgaaaa tgattttgtt ggaggccgtt cccctgttcc taaaacctat gacatgctaa 1260 aggctggcac aactgccact tatgaaggtc gctggggaag aggaacagca cagtacagct 1320 cccagaagtc cgtggaagaa aggtccttga ggcatcctct gaggagactg gagatttctc 1380 ctgacagcag cccggagagg gctcactaca cgcacagcga ttaccagtac agccagagaa 1440 gccaggctgg gcacaccctg caccaccaag aaagcaggcg ggccgccctc ctagtgccac 1500 cgagatatgc tcgttccgag atcgtggggg tcagccgtgc tggcaccaca agcaggcagc 1560 gccactttga cacataccac agacagtacc agcatggctc tgttagcgac accgtttttg 1620 acagcatccc tgccaacccg gccctgctca cgtaccccag gccagggacc agccgcagca 1680 tgggcaacct cttggagaag gagaactacc tgacggcagg gctcactgtc gggcaggtca 1740 ggccgctggt gcccctgcag cccgtcactc agaacagggc ttccaggtcc tcctggcatc 1800 agagctcctt ccacagcacc cgcacgctga gggaagctgg gcccagtgtc gccgtggatt 1860 ccagcgggag gagagcgcac ttgactgtcg gccaggcggc cgcaggggga agtgggaatc 1920 tgctcactga gagaagcact ttcactgact cccagctggg gaatgcagac atggagatga 1980 ctctggagcg agcagtgagt atgctcgagg cagaccacat gctgccatcc aggatttctg 2040 ctgcagctac tttcatacag cacgagtgct tccagaaatc tgaagctcgg aagagggtta 2100 accagcttcg tggcatcctc aagcttctgc agctcctaaa agttcagaat gaagacgttc 2160 agcgagctgt gtgtggggcc ttgagaaact tagtatttga agacaatgac aacaaattgg 2220 aggtggctga actaaatggg gtacctcggc tgctccaggt gctgaagcaa accagagact 2280 tggagactaa aaaacaaata acaggtttgc tgtggaattt gtcatctaat gacaaactca 2340 agaatctcat gataacagaa gcattgctta cgctgacgga gaatatcatc atcccctttt 2400 ctgggtggcc tgaaggagac tacccaaaag caaatggttt gctcgatttt gacatattct 2460 acaacgtcac tggatgccta agaaacatga gttctgctgg cgctgatggg agaaaagcga 2520 tgagaagatg tgacggactc attgactcac tggtccatta tgtcagagga accattgcag 2580 attaccagcc agatgacaag gccacggaga attgtgtgtg cattcttcat aacctctcct 2640 accagctgga ggcagagctc ccagagaaat attcccagaa tatctatatt caaaaccgga 2700 atatccagac tgacaacaac aaaagtattg gatgttttgg cagtcgaagc aggaaagtaa 2760 aagagcaata ccaggacgtg ccgatgccgg aggaaaagag caaccccaag ggcgtggagt 2820 ggctgtggca ttccattgtt ataaggatgt atctgtcctt gatcgccaaa agtgtccgca 2880 actacacaca agaagcatcc ttaggagctc tgcagaacct cacggccgga agtggaccaa 2940 tgccgacatc agtggctcag acagttgtcc agaaggaaag tggcctgcag cacacccgaa 3000 agatgctgca tgttggtgac ccaagtgtga aaaagacagc catctcgctg ctgaggaatc 3060 tgtcccggaa tctttctctg cagaatgaaa ttgccaaaga aactctccct gatttggttt 3120 ccatcattcc tgacacagtc ccgagtactg accttctcat tgaaactaca gcctctgcct 3180 gttacacatt gaacaacata atccaaaaca gttaccagaa tgcacgcgac cttctaaaca 3240 ccgggggcat ccagaaaatt atggccatta gtgcaggcga tgcctatgcc tccaacaaag 3300 caagtaaagc tgcttccgtc cttctgtatt ctctgtgggc acacacggaa ctgcatcatg 3360 cctacaagaa ggctcagttt aagaagacag attttgtcaa cagccggact gccaaagcct 3420 accactccct taaagactga tcaacctctg gattacaaaa tttgtgaaag attgactggt 3480 attcttaact atgttgctcc ttttacgcta tgtggatacg ctgctttaat gcctttgtat 3540 catgctattg cttcccgtat ggctttcatt ttctcctcct tgtataaatc ctggttgctg 3600 tctctttatg aggagttgtg gcccgttgtc aggcaacgtg gcgtggtgtg cactgtgttt 3660 gctgacgcaa cccccactgg ttggggcatt gccaccacct gtcagctcct ttccgggact 3720

ttcgctttcc ccctccctat tgccacggcg gaactcatcg ccgcctgcct tgcccgctgc 3780 tggacagggg ctcggctgtt gggcactgac aattccgtgg tgttgtcggg gaaatcatcg 3840 tcctttcctt ggctgctcgc ctgtgttgcc acctggattc tgcgcgggac gtccttctgc 3900 tacgtccctt cggccctcaa tccagcggac cttccttccc gcggcctgct gccggctctg 3960 cggcctcttc cgcgtcttcg ccttcgccct cagacgagtc ggatctccct ttgggccgcc 4020 tccccgcatc attgcctgcc cgggtggcat ccctgtgacc cctccccagt gcctctcctg 4080 gccctggaag ttgccactcc agtgcccacc agccttgtcc taataaaatt aagttgcatc 4140 attttgtctg actaggtgtc cttctataat attatggggt ggaggggggt ggtatggagc 4200 aaggggccca agttgggaag aaacctgtag ggcctgc 4237 <210> SEQ ID NO 94 <211> LENGTH: 3861 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Made in Lab - expression cassette polynucleotide <400> SEQUENCE: 94 ctcagtccat taggagccag tagcctggaa gatgtcttta cccccagcat cagttcaagt 60 ggagcagcac ataactcttg ccctctgcct tccaagattc tggtgctgag acttatggag 120 tgtcttggag gttgccttct gccccccaac cctgctccca gctggccctc ccaggcctgg 180 gttgctggcc tctgctttat caggattctc aagagggaca gctggtttat gttgcatgac 240 tgttccctgc atatctgctc tggttttaaa tagcttatct gagcagctgg aggaccacat 300 gggcttatat ggcgtggggt acatgttcct gtagccttgt ccctggcacc tgccaaaata 360 gcagccaaca ccccccaccc ccaccgccat ccccctgccc cacccgtccc ctgtcgcaca 420 ttcctccctc cgcagggctg gctcaccagg ccccagccca catgcctgct taaagccctc 480 tccatcctct gcctcaccca gtccccgctg agactgagca gacgcctcca ggatctgtcg 540 gcaggccacc atggcagccc ccggcgcccc agctgagtac ggctacatcc ggaccgtcct 600 gggccagcag atcctgggac aactggacag ctccagcctg gcgctgccct ccgaggccaa 660 gctgaagctg gcggggagca gcggccgcgg cggccagaca gtcaagagcc tgcggatcca 720 ggagcaggtg cagcagaccc tcgcccggaa gggccgcagc tccgtgggca acggaaatct 780 tcaccgaacc agcagtgttc ctgagtatgt ctacaaccta cacttggttg aaaatgattt 840 tgttggaggc cgttcccctg ttcctaaaac ctatgacatg ctaaaggctg gcacaactgc 900 cacttatgaa ggtcgctggg gaagaggaac agcacagtac agctcccaga agtccgtgga 960 agaaaggtcc ttgaggcatc ctctgaggag actggagatt tctcctgaca gcagcccgga 1020 gagggctcac tacacgcaca gcgattacca gtacagccag agaagccagg ctgggcacac 1080 cctgcaccac caagaaagca ggcgggccgc cctcctagtg ccaccgagat atgctcgttc 1140 cgagatcgtg ggggtcagcc gtgctggcac cacaagcagg cagcgccact ttgacacata 1200 ccacagacag taccagcatg gctctgttag cgacaccgtt tttgacagca tccctgccaa 1260 cccggccctg ctcacgtacc ccaggccagg gaccagccgc agcatgggca acctcttgga 1320 gaaggagaac tacctgacgg cagggctcac tgtcgggcag gtcaggccgc tggtgcccct 1380 gcagcccgtc actcagaaca gggcttccag gtcctcctgg catcagagct ccttccacag 1440 cacccgcacg ctgagggaag ctgggcccag tgtcgccgtg gattccagcg ggaggagagc 1500 gcacttgact gtcggccagg cggccgcagg gggaagtggg aatctgctca ctgagagaag 1560 cactttcact gactcccagc tggggaatgc agacatggag atgactctgg agcgagcagt 1620 gagtatgctc gaggcagacc acatgctgcc atccaggatt tctgctgcag ctactttcat 1680 acagcacgag tgcttccaga aatctgaagc tcggaagagg gttaaccagc ttcgtggcat 1740 cctcaagctt ctgcagctcc taaaagttca gaatgaagac gttcagcgag ctgtgtgtgg 1800 ggccttgaga aacttagtat ttgaagacaa tgacaacaaa ttggaggtgg ctgaactaaa 1860 tggggtacct cggctgctcc aggtgctgaa gcaaaccaga gacttggaga ctaaaaaaca 1920 aataacaggt ttgctgtgga atttgtcatc taatgacaaa ctcaagaatc tcatgataac 1980 agaagcattg cttacgctga cggagaatat catcatcccc ttttctgggt ggcctgaagg 2040 agactaccca aaagcaaatg gtttgctcga ttttgacata ttctacaacg tcactggatg 2100 cctaagaaac atgagttctg ctggcgctga tgggagaaaa gcgatgagaa gatgtgacgg 2160 actcattgac tcactggtcc attatgtcag aggaaccatt gcagattacc agccagatga 2220 caaggccacg gagaattgtg tgtgcattct tcataacctc tcctaccagc tggaggcaga 2280 gctcccagag aaatattccc agaatatcta tattcaaaac cggaatatcc agactgacaa 2340 caacaaaagt attggatgtt ttggcagtcg aagcaggaaa gtaaaagagc aataccagga 2400 cgtgccgatg ccggaggaaa agagcaaccc caagggcgtg gagtggctgt ggcattccat 2460 tgttataagg atgtatctgt ccttgatcgc caaaagtgtc cgcaactaca cacaagaagc 2520 atccttagga gctctgcaga acctcacggc cggaagtgga ccaatgccga catcagtggc 2580 tcagacagtt gtccagaagg aaagtggcct gcagcacacc cgaaagatgc tgcatgttgg 2640 tgacccaagt gtgaaaaaga cagccatctc gctgctgagg aatctgtccc ggaatctttc 2700 tctgcagaat gaaattgcca aagaaactct ccctgatttg gtttccatca ttcctgacac 2760 agtcccgagt actgaccttc tcattgaaac tacagcctct gcctgttaca cattgaacaa 2820 cataatccaa aacagttacc agaatgcacg cgaccttcta aacaccgggg gcatccagaa 2880 aattatggcc attagtgcag gcgatgccta tgcctccaac aaagcaagta aagctgcttc 2940 cgtccttctg tattctctgt gggcacacac ggaactgcat catgcctaca agaaggctca 3000 gtttaagaag acagattttg tcaacagccg gactgccaaa gcctaccact cccttaaaga 3060 ctgatcaacc tctggattac aaaatttgtg aaagattgac tggtattctt aactatgttg 3120 ctccttttac gctatgtgga tacgctgctt taatgccttt gtatcatgct attgcttccc 3180 gtatggcttt cattttctcc tccttgtata aatcctggtt gctgtctctt tatgaggagt 3240 tgtggcccgt tgtcaggcaa cgtggcgtgg tgtgcactgt gtttgctgac gcaaccccca 3300 ctggttgggg cattgccacc acctgtcagc tcctttccgg gactttcgct ttccccctcc 3360 ctattgccac ggcggaactc atcgccgcct gccttgcccg ctgctggaca ggggctcggc 3420 tgttgggcac tgacaattcc gtggtgttgt cggggaaatc atcgtccttt ccttggctgc 3480 tcgcctgtgt tgccacctgg attctgcgcg ggacgtcctt ctgctacgtc ccttcggccc 3540 tcaatccagc ggaccttcct tcccgcggcc tgctgccggc tctgcggcct cttccgcgtc 3600 ttcgccttcg ccctcagacg agtcggatct ccctttgggc cgcctccccg catcattgcc 3660 tgcccgggtg gcatccctgt gacccctccc cagtgcctct cctggccctg gaagttgcca 3720 ctccagtgcc caccagcctt gtcctaataa aattaagttg catcattttg tctgactagg 3780 tgtccttcta taatattatg gggtggaggg gggtggtatg gagcaagggg cccaagttgg 3840 gaagaaacct gtagggcctg c 3861 <210> SEQ ID NO 95 <211> LENGTH: 4369 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Made in Lab - expression cassette polynucleotide <400> SEQUENCE: 95 acccttcaga ttaaaaataa ctgaggtaag ggcctgggta ggggaggtgg tgtgagacgc 60 tcctgtctct cctctatctg cccatcggcc ctttggggag gaggaatgtg cccaaggact 120 aaaaaaaggc catggagcca gaggggcgag ggcaacagac ctttcatggg caaaccttgg 180 ggccctgctg tctagcatgc cccactacgg gtctaggctg cccatgtaag gaggcaaggc 240 ctggggacac ccgagatgcc tggttataat taacccagac atgtggctgc cccccccccc 300 ccaacacctg ctgcctctaa aaataaccct gtccctggtg gatcccctgc atgcgaagat 360 cttcgaacaa ggctgtgggg gactgagggc aggctgtaac aggcttgggg gccagggctt 420 atacgtgcct gggactccca aagtattact gttccatgtt cccggcgaag ggccagctgt 480 cccccgccag ctagactcag cacttagttt aggaaccagt gagcaagtca gcccttgggg 540 cagcccatac aaggccatgg ggctgggcaa gctgcacgcc tgggtccggg gtgggcacgg 600 tgcccgggca acgagctgaa agctcatctg ctctcagggg cccctccctg gggacagccc 660 ctcctggcta gtcacaccct gtaggctcct ctatataacc caggggcaca ggggctgccc 720 tcattctacc accacctcca cagcacagac agacactcag gagccagcca gggtaagttt 780 agtctttttg tcttttattt caggtcccgg atccggtggt ggtgcaaatc aaagaactgc 840 tcctcagtgg atgttgcctt tacttctagg cctgtacgga agtgttactt ctgctctaaa 900 agctgcggaa ttgtacccgc gccaccatgg cagcccccgg cgccccagct gagtacggct 960 acatccggac cgtcctgggc cagcagatcc tgggacaact ggacagctcc agcctggcgc 1020 tgccctccga ggccaagctg aagctggcgg ggagcagcgg ccgcggcggc cagacagtca 1080 agagcctgcg gatccaggag caggtgcagc agaccctcgc ccggaagggc cgcagctccg 1140 tgggcaacgg aaatcttcac cgaaccagca gtgttcctga gtatgtctac aacctacact 1200 tggttgaaaa tgattttgtt ggaggccgtt cccctgttcc taaaacctat gacatgctaa 1260 aggctggcac aactgccact tatgaaggtc gctggggaag aggaacagca cagtacagct 1320 cccagaagtc cgtggaagaa aggtccttga ggcatcctct gaggagactg gagatttctc 1380 ctgacagcag cccggagagg gctcactaca cgcacagcga ttaccagtac agccagagaa 1440 gccaggctgg gcacaccctg caccaccaag aaagcaggcg ggccgccctc ctagtgccac 1500 cgagatatgc tcgttccgag atcgtggggg tcagccgtgc tggcaccaca agcaggcagc 1560 gccactttga cacataccac agacagtacc agcatggctc tgttagcgac accgtttttg 1620 acagcatccc tgccaacccg gccctgctca cgtaccccag gccagggacc agccgcagca 1680 tgggcaacct cttggagaag gagaactacc tgacggcagg gctcactgtc gggcaggtca 1740 ggccgctggt gcccctgcag cccgtcactc agaacagggc ttccaggtcc tcctggcatc 1800 agagctcctt ccacagcacc cgcacgctga gggaagctgg gcccagtgtc gccgtggatt 1860 ccagcgggag gagagcgcac ttgactgtcg gccaggcggc cgcaggggga agtgggaatc 1920 tgctcactga gagaagcact ttcactgact cccagctggg gaatgcagac atggagatga 1980 ctctggagcg agcagtgagt atgctcgagg cagaccacat gctgccatcc aggatttctg 2040 ctgcagctac tttcatacag cacgagtgct tccagaaatc tgaagctcgg aagagggtta 2100 accagcttcg tggcatcctc aagcttctgc agctcctaaa agttcagaat gaagacgttc 2160 agcgagctgt gtgtggggcc ttgagaaact tagtatttga agacaatgac aacaaattgg 2220 aggtggctga actaaatggg gtacctcggc tgctccaggt gctgaagcaa accagagact 2280 tggagactaa aaaacaaata acagaccata cagtcaattt aagaagtagg aatggctggc 2340 cgggcgcggt ggctcacgcc tgtaatccca gcactttggg aggccaaggc gggcggatca 2400

cgaggtcagg agttcgagac cagcctgacc aacatggttt gctgtggaat ttgtcatcta 2460 atgacaaact caagaatctc atgataacag aagcattgct tacgctgacg gagaatatca 2520 tcatcccctt ttctgggtgg cctgaaggag actacccaaa agcaaatggt ttgctcgatt 2580 ttgacatatt ctacaacgtc actggatgcc taagaaacat gagttctgct ggcgctgatg 2640 ggagaaaagc gatgagaaga tgtgacggac tcattgactc actggtccat tatgtcagag 2700 gaaccattgc agattaccag ccagatgaca aggccacgga gaattgtgtg tgcattcttc 2760 ataacctctc ctaccagctg gaggcagagc tcccagagaa atattcccag aatatctata 2820 ttcaaaaccg gaatatccag actgacaaca acaaaagtat tggatgtttt ggcagtcgaa 2880 gcaggaaagt aaaagagcaa taccaggacg tgccgatgcc ggaggaaaag agcaacccca 2940 agggcgtgga gtggctgtgg cattccattg ttataaggat gtatctgtcc ttgatcgcca 3000 aaagtgtccg caactacaca caagaagcat ccttaggagc tctgcagaac ctcacggccg 3060 gaagtggacc aatgccgaca tcagtggctc agacagttgt ccagaaggaa agtggcctgc 3120 agcacacccg aaagatgctg catgttggtg acccaagtgt gaaaaagaca gccatctcgc 3180 tgctgaggaa tctgtcccgg aatctttctc tgcagaatga aattgccaaa gaaactctcc 3240 ctgatttggt ttccatcatt cctgacacag tcccgagtac tgaccttctc attgaaacta 3300 cagcctctgc ctgttacaca ttgaacaaca taatccaaaa cagttaccag aatgcacgcg 3360 accttctaaa caccgggggc atccagaaaa ttatggccat tagtgcaggc gatgcctatg 3420 cctccaacaa agcaagtaaa gctgcttccg tccttctgta ttctctgtgg gcacacacgg 3480 aactgcatca tgcctacaag aaggctcagt ttaagaagac agattttgtc aacagccgga 3540 ctgccaaagc ctaccactcc cttaaagact gatcaacctc tggattacaa aatttgtgaa 3600 agattgactg gtattcttaa ctatgttgct ccttttacgc tatgtggata cgctgcttta 3660 atgcctttgt atcatgctat tgcttcccgt atggctttca ttttctcctc cttgtataaa 3720 tcctggttgc tgtctcttta tgaggagttg tggcccgttg tcaggcaacg tggcgtggtg 3780 tgcactgtgt ttgctgacgc aacccccact ggttggggca ttgccaccac ctgtcagctc 3840 ctttccggga ctttcgcttt ccccctccct attgccacgg cggaactcat cgccgcctgc 3900 cttgcccgct gctggacagg ggctcggctg ttgggcactg acaattccgt ggtgttgtcg 3960 gggaaatcat cgtcctttcc ttggctgctc gcctgtgttg ccacctggat tctgcgcggg 4020 acgtccttct gctacgtccc ttcggccctc aatccagcgg accttccttc ccgcggcctg 4080 ctgccggctc tgcggcctct tccgcgtctt cgccttcgcc ctcagacgag tcggatctcc 4140 ctttgggccg cctccccgca tcattgcctg cccgggtggc atccctgtga cccctcccca 4200 gtgcctctcc tggccctgga agttgccact ccagtgccca ccagccttgt cctaataaaa 4260 ttaagttgca tcattttgtc tgactaggtg tccttctata atattatggg gtggaggggg 4320 gtggtatgga gcaaggggcc caagttggga agaaacctgt agggcctgc 4369 <210> SEQ ID NO 96 <211> LENGTH: 3993 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Made in Lab - expression cassette polynucleotide <400> SEQUENCE: 96 ctcagtccat taggagccag tagcctggaa gatgtcttta cccccagcat cagttcaagt 60 ggagcagcac ataactcttg ccctctgcct tccaagattc tggtgctgag acttatggag 120 tgtcttggag gttgccttct gccccccaac cctgctccca gctggccctc ccaggcctgg 180 gttgctggcc tctgctttat caggattctc aagagggaca gctggtttat gttgcatgac 240 tgttccctgc atatctgctc tggttttaaa tagcttatct gagcagctgg aggaccacat 300 gggcttatat ggcgtggggt acatgttcct gtagccttgt ccctggcacc tgccaaaata 360 gcagccaaca ccccccaccc ccaccgccat ccccctgccc cacccgtccc ctgtcgcaca 420 ttcctccctc cgcagggctg gctcaccagg ccccagccca catgcctgct taaagccctc 480 tccatcctct gcctcaccca gtccccgctg agactgagca gacgcctcca ggatctgtcg 540 gcaggccacc atggcagccc ccggcgcccc agctgagtac ggctacatcc ggaccgtcct 600 gggccagcag atcctgggac aactggacag ctccagcctg gcgctgccct ccgaggccaa 660 gctgaagctg gcggggagca gcggccgcgg cggccagaca gtcaagagcc tgcggatcca 720 ggagcaggtg cagcagaccc tcgcccggaa gggccgcagc tccgtgggca acggaaatct 780 tcaccgaacc agcagtgttc ctgagtatgt ctacaaccta cacttggttg aaaatgattt 840 tgttggaggc cgttcccctg ttcctaaaac ctatgacatg ctaaaggctg gcacaactgc 900 cacttatgaa ggtcgctggg gaagaggaac agcacagtac agctcccaga agtccgtgga 960 agaaaggtcc ttgaggcatc ctctgaggag actggagatt tctcctgaca gcagcccgga 1020 gagggctcac tacacgcaca gcgattacca gtacagccag agaagccagg ctgggcacac 1080 cctgcaccac caagaaagca ggcgggccgc cctcctagtg ccaccgagat atgctcgttc 1140 cgagatcgtg ggggtcagcc gtgctggcac cacaagcagg cagcgccact ttgacacata 1200 ccacagacag taccagcatg gctctgttag cgacaccgtt tttgacagca tccctgccaa 1260 cccggccctg ctcacgtacc ccaggccagg gaccagccgc agcatgggca acctcttgga 1320 gaaggagaac tacctgacgg cagggctcac tgtcgggcag gtcaggccgc tggtgcccct 1380 gcagcccgtc actcagaaca gggcttccag gtcctcctgg catcagagct ccttccacag 1440 cacccgcacg ctgagggaag ctgggcccag tgtcgccgtg gattccagcg ggaggagagc 1500 gcacttgact gtcggccagg cggccgcagg gggaagtggg aatctgctca ctgagagaag 1560 cactttcact gactcccagc tggggaatgc agacatggag atgactctgg agcgagcagt 1620 gagtatgctc gaggcagacc acatgctgcc atccaggatt tctgctgcag ctactttcat 1680 acagcacgag tgcttccaga aatctgaagc tcggaagagg gttaaccagc ttcgtggcat 1740 cctcaagctt ctgcagctcc taaaagttca gaatgaagac gttcagcgag ctgtgtgtgg 1800 ggccttgaga aacttagtat ttgaagacaa tgacaacaaa ttggaggtgg ctgaactaaa 1860 tggggtacct cggctgctcc aggtgctgaa gcaaaccaga gacttggaga ctaaaaaaca 1920 aataacagac catacagtca atttaagaag taggaatggc tggccgggcg cggtggctca 1980 cgcctgtaat cccagcactt tgggaggcca aggcgggcgg atcacgaggt caggagttcg 2040 agaccagcct gaccaacatg gtttgctgtg gaatttgtca tctaatgaca aactcaagaa 2100 tctcatgata acagaagcat tgcttacgct gacggagaat atcatcatcc ccttttctgg 2160 gtggcctgaa ggagactacc caaaagcaaa tggtttgctc gattttgaca tattctacaa 2220 cgtcactgga tgcctaagaa acatgagttc tgctggcgct gatgggagaa aagcgatgag 2280 aagatgtgac ggactcattg actcactggt ccattatgtc agaggaacca ttgcagatta 2340 ccagccagat gacaaggcca cggagaattg tgtgtgcatt cttcataacc tctcctacca 2400 gctggaggca gagctcccag agaaatattc ccagaatatc tatattcaaa accggaatat 2460 ccagactgac aacaacaaaa gtattggatg ttttggcagt cgaagcagga aagtaaaaga 2520 gcaataccag gacgtgccga tgccggagga aaagagcaac cccaagggcg tggagtggct 2580 gtggcattcc attgttataa ggatgtatct gtccttgatc gccaaaagtg tccgcaacta 2640 cacacaagaa gcatccttag gagctctgca gaacctcacg gccggaagtg gaccaatgcc 2700 gacatcagtg gctcagacag ttgtccagaa ggaaagtggc ctgcagcaca cccgaaagat 2760 gctgcatgtt ggtgacccaa gtgtgaaaaa gacagccatc tcgctgctga ggaatctgtc 2820 ccggaatctt tctctgcaga atgaaattgc caaagaaact ctccctgatt tggtttccat 2880 cattcctgac acagtcccga gtactgacct tctcattgaa actacagcct ctgcctgtta 2940 cacattgaac aacataatcc aaaacagtta ccagaatgca cgcgaccttc taaacaccgg 3000 gggcatccag aaaattatgg ccattagtgc aggcgatgcc tatgcctcca acaaagcaag 3060 taaagctgct tccgtccttc tgtattctct gtgggcacac acggaactgc atcatgccta 3120 caagaaggct cagtttaaga agacagattt tgtcaacagc cggactgcca aagcctacca 3180 ctcccttaaa gactgatcaa cctctggatt acaaaatttg tgaaagattg actggtattc 3240 ttaactatgt tgctcctttt acgctatgtg gatacgctgc tttaatgcct ttgtatcatg 3300 ctattgcttc ccgtatggct ttcattttct cctccttgta taaatcctgg ttgctgtctc 3360 tttatgagga gttgtggccc gttgtcaggc aacgtggcgt ggtgtgcact gtgtttgctg 3420 acgcaacccc cactggttgg ggcattgcca ccacctgtca gctcctttcc gggactttcg 3480 ctttccccct ccctattgcc acggcggaac tcatcgccgc ctgccttgcc cgctgctgga 3540 caggggctcg gctgttgggc actgacaatt ccgtggtgtt gtcggggaaa tcatcgtcct 3600 ttccttggct gctcgcctgt gttgccacct ggattctgcg cgggacgtcc ttctgctacg 3660 tcccttcggc cctcaatcca gcggaccttc cttcccgcgg cctgctgccg gctctgcggc 3720 ctcttccgcg tcttcgcctt cgccctcaga cgagtcggat ctccctttgg gccgcctccc 3780 cgcatcattg cctgcccggg tggcatccct gtgacccctc cccagtgcct ctcctggccc 3840 tggaagttgc cactccagtg cccaccagcc ttgtcctaat aaaattaagt tgcatcattt 3900 tgtctgacta ggtgtccttc tataatatta tggggtggag gggggtggta tggagcaagg 3960 ggcccaagtt gggaagaaac ctgtagggcc tgc 3993

Claims

1.-91. (canceled)

92. A method of treating arrhythmogenic right ventricular cardiomyopathy (ARVC) in a subject having a mutation in a PKP2 gene, comprising: administering to the subject a recombinant adeno-associated virus (rAAV) vector comprising a vector genome, wherein the vector genome comprises an expression cassette and flanking AAV inverted terminal repeats (ITRs), the expression cassette comprising a polynucleotide comprising: a polynucleotide sequence encoding a Plakophilin-2 (PKP2); a promoter sequence, wherein the promoter sequence is operatively linked to the polynucleotide sequence encoding the PKP2; and a polyA sequence, wherein the rAAV vector is an AAV9 vector, and wherein the method treats one or more symptoms of ARVC.

93. The method of claim 92, wherein the rAAV vector comprises a capsid protein that shares at least 95% polypeptide sequence identity to SEQ ID NO: 77.

94. The method of claim 92, wherein the rAAV vector comprises a capsid protein that shares 99% polypeptide sequence identity to SEQ ID NO: 77.

95. The method of claim 92, wherein the rAAV vector comprises a capsid protein that shares 100% polypeptide sequence identity to SEQ ID NO: 77.

96. The method of claim 92, wherein the promoter is a cardiac-specific promoter.

97. The method of claim 92, wherein the promoter is a muscle-specific promoter.

98. The method of claim 92, wherein the promoter is a cardiomyocyte-specific promoter.

99. The method of claim 98, wherein the promoter is a Myosin Heavy-chain Creatine Kinase 7 (MHCK7) promoter.

100. The method of claim 99, wherein the MHCK7 promoter shares at least 90% polynucleotide sequence identity with SEQ ID NO: 31.

101. The method of claim 99, wherein the MHCK7 promoter shares at least 95% polynucleotide sequence identity with SEQ ID NO: 31.

102. The method of claim 98, wherein the promoter is a cardiac troponin T (hTNNT2) promoter.

103. The method of claim 102, wherein the hTNNT2 promoter shares at least 90% polynucleotide sequence identity with SEQ ID NO: 33.

104. The method of claim 102, wherein the hTNNT2 promoter shares at least 95% polynucleotide sequence identity with SEQ ID NO: 33.

105. The method of claim 102, wherein the expression cassette comprises exon 1 of the cardiac troponin T (hTNNT2) gene.

106. The method of claim 105, where the hTNNT2 promoter and exon 1 together share at least 90% polynucleotide sequence identity with SEQ ID NO: 32.

107. The method of claim 102, wherein the polyA signal is a human growth hormone (hGH) polyA.

108. The method of claim 107, wherein the expression cassette comprises a Woodchuck Hepatitis Virus Posttranscriptional Regulatory Element (WPRE).

109. The method of claim 102, wherein the PKP2 is PKP2 isoform A.

110. The method of claim 109, wherein the PKP2 isoform A shares at least 90% polypeptide sequence identity with SEQ ID NO: 1.

111. The method of claim 102, wherein the PKP2 is PKP2 isoform B.

112. The method of claim 111, wherein the PKP2 isoform B shares at least 90% polypeptide sequence identity with SEQ ID NO: 2.

113. The method of claim 92, wherein the rAAV vector is administered by intravenous injection, intracardiac injection, intracardiac infusion, or cardiac catheterization.

114. The method of claim 92, wherein the rAAV vector is administered at a dose of between about 1.times.10.sup.13 and 5.times.10.sup.14 vg/kg.

115. The method of claim 92, wherein the rAAV vector is administered at a dose of between about 5.times.10.sup.13 and 3.times.10.sup.14 vg/kg.

116. The method of claim 92, wherein the rAAV vector is administered at a dose of about 2.times.10.sup.14 vg/kg.

117. The method of claim 92, wherein the method reduces a decrease in left ventricle ejection fraction percentage (LVEF %) compared to the decrease observed in an untreated subject identified as having a mutation in the PKP2 gene.

118. The method of claim 92, wherein the method reduces a decrease in left ventricle fractional shortening percentage (FS %) compared to the decrease observed in an untreated subject identified as having a mutation in the PKP2 gene.

119. The method of claim 92, wherein the method prevents an increase in right ventricle area in millimeters squared (RV Area (mm.sup.2)).

120. The method of claim 92, wherein the method increases survival compared to survival of untreated subjects identified as having a mutation in the PKP2 gene.

121. A recombinant adeno-associated virus (rAAV) vector comprising a vector genome, wherein the vector genome comprises an expression cassette and flanking AAV inverted terminal repeats (ITRs), the expression cassette comprising a polynucleotide comprising: a polynucleotide sequence encoding a Plakophilin-2 (PKP2); a promoter sequence, wherein the promoter sequence is operatively linked to the polynucleotide sequence encoding the PKP2; and a polyA sequence, and wherein the rAAV vector is an AAV9 vector.