Entries |
Document | Title | Date |
20090035862 | METHODS AND COMPOSITIONS FOR GENOMIC MODIFICATION - The present invention provides methods of site-specifically integrating a polynucleotide sequence of interest in a genome of a eucaryotic cell, as well as, enzymes, polypeptides, and a variety of vector constructs useful therefore. In the method, a targeting construct comprises, for example, (i) a first recombination site and a polynucleotide sequence of interest, and (ii) a site-specific recombinase, which are introduced into the cell. The genome of the cell comprises a second recombination site. Recombination between the first and second recombination sites is facilitated by the site-specific recombinase. The invention describes compositions, vectors, and methods of use thereof, for the generation of transgenic cells, tissues, plants, and animals. The compositions, vectors, and methods of the present invention are also useful in gene therapy techniques. | 02-05-2009 |
20090233368 | ALLELE SUPPRESSION - A strategy for suppressing expression of one allele of an endogenous gene is provided comprising providing suppression effectors such as antisense nucleic acids able to bind to polymorphisms within or adjacent to a gene such that one allele of a gene is exclusively or preferentially suppressed and if required of a replacement gene can be introduced. | 09-17-2009 |
20090239305 | Gene recombination exchange system for stable gene modification in human ES cells - A method of creating a human pluripotent transgenic stem cell, wherein heterologous DNA is inserted into specific “hot-spots” in the genome where stable and high gene expression may occur, is disclosed. In one embodiment, the method comprises the steps of: (a) selecting a pluripotent stem cell line, and (b) inserting heterologous DNA at an insertion site selected from the group consisting of insertion site one and insertion site two to form a transgenic cell line. In another embodiment, the heterologous DNA is an exchange cassette and the transgenic cell line formed is a master cell line. | 09-24-2009 |
20100068815 | SITE-SPECIFIC RECOMBINATION SYSTEMS FOR USE IN EUKARYOTIC CELLS - Prokaryotic recombination systems have been adapted to function in eukaryotes in order to achieve one or more of the following: DNA site specific excision, translocation, integration and inversion. These recombination systems are identified as seven members of the small serine resolvase subfamily: CinH, ParA, Tn1721, Tn5053, Tn21, Tn402, and Tn501 and three members of the large serine resolvase subfamily: Bxb1, U153, and TP901-1. These recombination systems represent new tools for the genetic manipulation of eukaryotic genomes. | 03-18-2010 |
20110136237 | SITE-SPECIFIC RECOMBINATION SYSTEMS FOR USE IN EUKARYOTIC CELLS - Prokaryotic recombination systems have been adapted to function in eukaryotes in order to achieve one or more of the following: DNA site specific excision, translocation, integration and inversion. These recombination systems are identified as seven members of the small serine resolvase subfamily: CinH, ParA, Tn1721, Tn5053, Tn21, Tn402, and Tn501 and three members of the large serine resolvase subfamily: Bxb1, U153, and TP901-1. These recombination systems represent new tools for the genetic manipulation of eukaryotic genomes. | 06-09-2011 |
20110177600 | PROTEIN PRODUCTION USING EUKARYOTIC CELL LINES - The subject invention provides a site-specific integration system and methods for generating eukaryotic cells lines for protein production. The provided system includes a first site-specifically integrating target vector and a second site-specifically integrating donor vector comprising a gene of interest. Also provided are mammalian cell lines produced by the subject methods and systems, as well as kits that include the subject systems. | 07-21-2011 |
20110207226 | NON-INTEGRATING LENTI/ADENO-ASSOCIATED VIRUS HYBRID VECTOR SYSTEM - The present invention provides for a hybrid vector system for the purpose of therapeutic gene delivery where the system is used for a targeted integration of a therapeutic gene into a genome. The hybrid vector system comprises a hybrid vector made up of a non-integrating lentiviral vector and an adeno-associated vector, and a therapeutic gene. | 08-25-2011 |
20120107938 | METHODS AND KITS FOR HIGH EFFICIENCY ENGINEERING OF CONDITIONAL MOUSE ALLELES - The present invention concerns methods and kits for the direct, targeted engineering of conditional alleles in rodent embryonic stem cells in which the conditional allele is replaced with a DNA of interest without first introducing heterotypic recombination sites, thus providing high efficiency targeted exchange of genetic material. | 05-03-2012 |
20120214241 | ZINC FINGER NUCLEASE MODIFICATION OF LEUCINE RICH REPEAT KINASE 2 (LRRK2) MUTANT FIBROBLASTS AND IPSCS - Disclosed herein are methods and compositions for alteration of an LRRK2 gene in a fibroblast or iPSC. | 08-23-2012 |
20120214242 | CRE-LOX BASED GENE KNOCKDOWN CONSTRUCTS AND METHODS OF USE THEREOF - The present invention relates to vectors, compositions and methods for conditional, Cre-lox regulated, RNA interference. The vectors allow for spatial and temporal control of miRNA expression in vivo. | 08-23-2012 |
20120258541 | CHROMOSOMAL LANDING PADS AND RELATED USES - Provided herein are methods for stable integration and/or expression of one or more recombinant polynucleotides in a host cell. The recombinant polynucleotides are typically integrated into the host genome at some native chromosomal integration sites. The integration can be mediated by homologous recombination or by using a hybrid recombinase targeting the specific chromosomal locations. The native chromosomal integration sites in the host cells, which support stable integration and strong transcription activities of foreign genes, are present within or adjacent to specific genes in the CHO genome, ankyrin 2 gene (Ank2), cleavage and polyadenylation specific factor 4 gene (Cpsf4), C-Mos gene, and Nephrocystin-1/Mal gene. Also provided are methods and nucleic acid molecules for inserting site-specific recombination sequences (chromosomal landing pads) into these specific chromosomal locations, engineered host cells containing chromosomal landing pads, methods and compositions (e.g., kits) therefore. | 10-11-2012 |
20130045539 | MEGANUCLEASE RECOMBINATION SYSTEM - The invention relates to a set of genetic constructs which comprises at least a first recombinogenic construct (i) with at least two portions homologous to the genomic regions preceding and following the DNA target site of a site specific endonuclease and also comprising both a negative selection and positive selection mark interposed with the homologous portions as well as a region into which a sequence of interest can be cloned adjacent to the positive selection marker; and a second construct (ii, iii or iv) comprising the meganuclease. The present invention also relates to a kit comprising these constructs and methods to use this set of constructs to introduce into the genome of a target cell, tissue or organism a sequence of interest. | 02-21-2013 |
20130052739 | NOVEL FRT RECOMBINATION SITES AND METHODS OF USE - Methods and compositions using populations of randomized modified FRT recombination sites to identify, isolate and/or characterize modified FRT recombination sites are provided. The recombinogenic modified FRT recombination sites can be employed in a variety of methods for targeted recombination of polynucleotides of interest, including methods to recombine polynucleotides, assess promoter activity, directly select transformed organisms, minimize or eliminate expression resulting from random integration into the genome of an organism, such as a plant, remove polynucleotides of interest, combine multiple transfer cassettes, invert or excise a polynucleotide, and identify and/or characterize transcriptional regulating regions are also provided. | 02-28-2013 |
20130059387 | MEGANUCLEASE VARIANTS CLEAVING A DNA TARGET SEQUENCE FROM THE HPRT GENE AND USES THEREOF - A method for inducing a site-specific modification in the HPRT gene, for a non-therapeutic purpose, by contacting a DNA target sequence selected from the group consisting of the sequences SEQ ID NO: 1 to 14 thereby cleaving the DNA target with an I-CreI variant or single-chain derivative having at least one substitution in one of the two functional subdomains of the LAGLIDADG (SEQ ID NO: 153) core domain situated from positions 26 to 40 and 44 to 77 of I-CreI. | 03-07-2013 |
20130059388 | METHODS FOR GENERATING ENDOGENOUSLY TAGGED PROTEINS - The present disclosure provides a method for endogenously tagging an endogenous protein in a cell, and a cell comprising an endogenously tagged protein. Also described are cells produced using such a method and a kit comprising a cell having tagged endogenous protein. | 03-07-2013 |
20130065310 | USE OF ENDOGENOUS PROMOTERS TO EXPRESS HETEROLOGOUS PROTEINS - The present invention provides methods for using endogenous transcriptional control systems to regulate the expression of heterologous protein(s). In particular, targeted genome editing is used to integrate a sequence encoding the heterologous protein(s) in-frame with an endogenous coding sequence such that the expression of the heterologous and endogenous sequences is regulated by the endogenous control system. | 03-14-2013 |
20130102080 | METHODS FOR REPROGRAMMING SOMATIC CELLS - The invention provides methods for reprogramming somatic cells to generate multipotent or pluripotent cells. Such methods are useful for a variety of purposes, including treating or preventing a medical condition in an individual. The invention further provides methods for identifying an agent that reprograms somatic cells to a less differentiated state. | 04-25-2013 |
20130137180 | GENOME EDITING USING TARGETING ENDONUCLEASES AND SINGLE-STRANDED NUCLEIC ACIDS - The present invention provides methods and kits for editing specific chromosomal sequences in cells. In particular, targeting endonucleases and single-stranded nucleic acids are used to edit the chromosomal sequence. | 05-30-2013 |
20130149786 | I-CREI VARIANTS WITH NEW SPECIFICITY AND METHODS OF THEIR GENERATION - The present invention relates to 1-Cre1 variants which can in particular recognise and cleave DNA targets which do not comprise the same nucleotides at positions ±6 and ±7 which are present in the wild type 1-Cre1 target. The present invention also relates to 1-Cre1 variants which can recognise and cleave targets which do not comprise the wild type nucleotides at positions ±4, ±5, ±6, ±7 and to 1-Cre1 variants with new specificity which can recognise and cleave targets which do not comprise the wild type nucleotides at positions ±4, ±5, ±6, ±7, ±8, ±9 and ±10. | 06-13-2013 |
20130171731 | REVERSIBLY IMMORTALIZED CELLS AS WELL AS METHODS RELATING HERETO - The present invention relates to methods of producing a reversibly immortalized cell, cells obtainable by the above method, eukaryotic cells comprising one or more nucleic acid(s) coding for one or more immortalizing protein(s) and methods of re-differentiating these cells. | 07-04-2013 |
20130171732 | METHODS AND COMPOSITIONS FOR REGULATING HIV INFECTION - Methods and compositions for regulating HIV infection and/or replication in which an anti-HIV transgene is integrated into the genome of a cell using a nuclease. | 07-04-2013 |
20130217131 | GENOME ENGINEERING VIA DESIGNED TAL EFFECTOR NUCLEASES - The present invention relates to a fusion protein having a TAL (transcription activator-like) effector (TALE) domain and a nucleotide cleavage domain, and more particularly, to the TAL effector nuclease comprising a TAL (transcription activator-like) effector (TALE) domain and a nucleotide cleavage domain, wherein the TALE domain includes one or more TALE-repeat modules, each of the TALE-repeat modules recognizing a single specific nucleic acid, and a use thereof. | 08-22-2013 |
20130224863 | RATIONALLY-DESIGNED MEGANUCLEASES WITH RECOGNITION SEQUENCES FOUND IN DNASE HYPERSENSITIVE REGIONS OF THE HUMAN GENOME - Rationally-designed LAGLIDADG meganucleases and methods of making such meganucleases are provided. In addition, methods are provided for using the meganucleases to generate recombinant cells and organisms having a desired DNA sequence inserted into a limited number of loci within the genome, as well as methods of gene therapy, for treatment of pathogenic infections, and for in vitro applications in diagnostics and research. | 08-29-2013 |
20130230925 | MOLECULAR SWITCHES AND METHODS FOR MAKING AND USING THE SAME - The invention provides molecular switches which couple external signals to functionality and to methods of making and using the same. The switches according to the invention can be used, for example, to regulate gene transcription, target drug delivery to specific cells, transport drugs intracellularly, control drug release, provide conditionally active proteins, perform metabolic engineering, and modulate cell signaling pathways. Libraries comprising the switches and expression vectors and host cells for expressing the switches are also provided. | 09-05-2013 |
20130244332 | TAREGTED INTEGRATION AND EXPRESSION OF EXOGENOUS NUCLEIC ACID SEQUENCES - Disclosed herein are methods and compositions for targeted integration of a exogenous sequence into a predetermined target site in a genome for use, for example, in protein expression and gene inactivation. | 09-19-2013 |
20130302899 | MULTIFUNCTIONAL ALLELES - Nucleic acid constructs and methods for rendering modifications to a genome are provided, wherein the modifications comprise null alleles, conditional alleles and null alleles comprising COINs. Multifunctional alleles (MFA) are provided, as well as methods for making them, which afford the ability in a single targeting to introduce an allele that can be used to generate a null allele, a conditional allele, or an allele that is a null allele and that further includes a COIN. MFAs comprise pairs of cognate recombinase recognition sites, an actuating sequence and/or a drug selection cassette, and a nucleotide sequence of interest, and a COIN, wherein upon action of a recombinase a conditional allele with a COIN is formed. In a further embodiment, action of a second recombinase forms an allele that contains only a COIN in sense orientation. In a further embodiment, action by a third recombinase forms an allele that contains only the actuating sequence in sense orientation. | 11-14-2013 |
20140004608 | MEGANUCLEASE RECOMBINATION SYSTEM | 01-02-2014 |
20140038292 | Tol1 FACTOR TRANSPOSASE AND DNA INTRODUCTION SYSTEM USING THE SAME - An object is to provide a Tol1 element transposase and a use thereof. Provided is a Tol1 element transposase containing (a) a protein having the amino acid sequence of SEQ ID No: 1 or (b) a protein having an amino acid sequence homologous to the amino acid sequence of SEQ ID NO: 1 and having an enzymatic activity for transferring Tol1 element. Further, provided is a polynucleotide encoding the transposase and an expression construct containing the polynucleotide therein. The present invention also provides a DNA introduction system including (a) a donor factor having such a structure that a desired DNA is inserted in a transposase gene-defected Tol1 element and (b) a helper factor containing the transposase or the polynucleotide. | 02-06-2014 |
20140080216 | METHODS AND COMPOSITIONS FOR TREATMENT OF A GENETIC CONDITION - Methods and compositions for a genetic disease are provided. | 03-20-2014 |
20140113375 | Transient Expression And Reverse Transcription Aided Genome Alteration System - Disclosed are methods and cellular systems for the generation of predetermined or random alterations at specific genomic location. The invention provides a transient expression and reverse transcription system to generate single-stranded DNA sequences homologous to a target genomic sequence, which can be transported to the nucleus to alter the genetic information of the target genomic sequence. Also provided are cellular and molecular components that can be used to increase the efficiency of the targeted genomic modification process. | 04-24-2014 |
20140120622 | T CELL MODIFYING COMPOUNDS AND USES THEREOF - Methods and compositions for modifying T-cells in which PD1 and/or CTLA-4 is repressed and/or inactivated using fusion proteins such as artificial transcription factors and nucleases. | 05-01-2014 |
20140127814 | GENERATION AND USE OF PLURIPOTENT STEM CELLS - ABSTRACT Methods, compositions, constructs, vectors, cell lines, and kits, for generating induced pluripotent stem cells by site-specific integration of pluripotency coding sequences with endonucleases for use in gene therapy, regenerative medicine, cell therapy or drug screening. | 05-08-2014 |
20140134739 | METHOD OF GENETICALLY ALTERING AND PRODUCING ALLERGY FREE CATS - A transgenic cat with a phenotype characterized by the substantial absence of the major cat allergen, Fel d I. The phenotype is conferred in the transgenic cat by disrupting the coding sequence of the target gene with a specialized construct. The phenotype of the transgenic cat is transmissible to its offspring. | 05-15-2014 |
20140134740 | NOVEL DNA-BINDING PROTEINS AND USES THEREOF - Disclosed herein are polypeptides, polynucleotides encoding, cells and organisms comprising novel DNA-binding domains, including TALE DNA-binding domains. Also disclosed are methods of using these novel DNA-binding domains for modulation of gene expression and/or genomic editing of endogenous cellular sequences. | 05-15-2014 |
20140134741 | NOVEL DNA-BINDING PROTEINS AND USES THEREOF - Disclosed herein are polypeptides, polynucleotides encoding, cells and organisms comprising novel DNA-binding domains, including TALE DNA-binding domains. Also disclosed are methods of using these novel DNA-binding domains for modulation of gene expression and/or genomic editing of endogenous cellular sequences. | 05-15-2014 |
20140170753 | CRISPR-CAS SYSTEMS AND METHODS FOR ALTERING EXPRESSION OF GENE PRODUCTS - The invention provides for systems, methods, and compositions for altering expression of target gene sequences and related gene products. Provided are vectors and vector systems, some of which encode one or more components of a CRISPR complex, as well as methods for the design and use of such vectors. Also provided are methods of directing CRISPR complex formation in eukaryotic cells and methods for utilizing the CRISPR-Cas system. | 06-19-2014 |
20140179005 | Methods and Products for Producing Engineered Mammalian Cell Lines With Amplified Transgenes - Methods of inserting genes into defined locations in the chromosomal DNA of cultured mammalian cell lines which are subject to gene amplification are disclosed. In particular, sequences of interest (e.g., genes encoding biotherapeutic proteins) are inserted proximal to selectable genes in amplifiable loci, and the transformed cells are subjected to selection to induce co-amplification of the selectable gene and the sequence of interest. The invention also relates to meganucleases, vectors and engineered cell lines necessary for performing the methods, to cell lines resulting from the application of the methods, and use of the cell lines to produce protein products of interest. | 06-26-2014 |
20140179006 | CRISPR-CAS COMPONENT SYSTEMS, METHODS AND COMPOSITIONS FOR SEQUENCE MANIPULATION - The invention provides for systems, methods, and compositions for manipulation of sequences and/or activities of target sequences. Provided are vectors and vector systems, some of which encode one or more components of a CRISPR complex, as well as methods for the design and use of such vectors. Also provided are methods of directing CRISPR complex formation in eukaryotic cells and methods for selecting specific cells by introducing precise mutations utilizing the CRISPR/Cas system. | 06-26-2014 |
20140186958 | ENGINEERING AND OPTIMIZATION OF SYSTEMS, METHODS AND COMPOSITIONS FOR SEQUENCE MANIPULATION WITH FUNCTIONAL DOMAINS - The invention provides for engineering and optimization of systems, methods, and compositions for manipulation of sequences and/or activities of target sequences. Provided are vectors and vector systems, some of which encode one or more components of a CRISPR complex, as well as methods for the design and use of such vectors with additional functional domains. Also provided are methods of directing CRISPR complex formation in prokaryotic and eukaryotic cells to ensure enhanced specificity for target recognition and avoidance of toxicity. | 07-03-2014 |
20140193914 | Introduction of Modular Vector Elements During Production of a Lentivirus - Methods and kits for lentiviral production are provided. By separating certain components of the vector including but not limited to promoter, reporter and selection marker preference components from the genetic content of interest, one can create libraries that allow for the efficient generation of custom selected lentiviral vectors. | 07-10-2014 |
20140242702 | METHODS AND COMPOSITIONS FOR ENHANCING NUCLEASE-MEDIATED GENE DISRUPTION - Methods and compositions for increasing nuclease-mediated genomic modification using DNA repair inhibitors are provided. | 08-28-2014 |
20140248702 | CRISPR-Cas Nickase Systems, Methods And Compositions For Sequence Manipulation in Eukaryotes - The invention provides for systems, methods, and compositions for manipulation of sequences and/or activities of target sequences. Provided are vectors and vector systems, some of which encode one or more components of a CRISPR complex, as well as methods for the design and use of such vectors. Also provided are methods of directing CRISPR complex formation in eukaryotic cells and methods for selecting specific cells by introducing precise mutations utilizing the CRISPR/Cas system. | 09-04-2014 |
20140273230 | CRISPR-BASED GENOME MODIFICATION AND REGULATION - The present invention provides methods for modifying chromosomal sequences. In particular, methods are provided for using RNA-guided endonucleases or modified RNA-guided endonucleases to modify targeted chromosomal sequences. | 09-18-2014 |
20140273231 | CRISPR-CAS COMPONENT SYSTEMS, METHODS AND COMPOSITIONS FOR SEQUENCE MANIPULATION - The invention provides for systems, methods, and compositions for manipulation of sequences and/or activities of target sequences. Provided are vectors and vector systems, some of which encode one or more components of a CRISPR complex, as well as methods for the design and use of such vectors. Also provided are methods of directing CRISPR complex formation in eukaryotic cells and methods for selecting specific cells by introducing precise mutations utilizing the CRISPR/Cas system. | 09-18-2014 |
20140273232 | ENGINEERING OF SYSTEMS, METHODS AND OPTIMIZED GUIDE COMPOSITIONS FOR SEQUENCE MANIPULATION - The invention provides for systems, methods, and compositions for manipulation of sequences and/or activities of target sequences. Provided are vectors and vector systems, some of which encode one or more components of a CRISPR complex, as well as methods for the design and use of such vectors. Also provided are methods of directing CRISPR complex formation in eukaryotic cells and methods for selecting specific cells by introducing precise mutations utilizing the CRISPR-Cas system. | 09-18-2014 |
20140273233 | CRISPR-BASED GENOME MODIFICATION AND REGULATION - The present invention provides methods for modifying chromosomal sequences. In particular, methods are provided for using RNA-guided endonucleases or modified RNA-guided endonucleases to modify targeted chromosomal sequences. | 09-18-2014 |
20140273234 | ENGINEERING AND OPTIMIZATION OF IMPROVED SYSTEMS, METHODS AND ENZYME COMPOSITIONS FOR SEQUENCE MANIPULATION - The invention provides for engineering and optimization of systems, methods, and compositions for manipulation of sequences and/or activities of target sequences. Provided are compositions and methods related to components of a CRISPR complex particularly comprising a Cas ortholog enzyme. | 09-18-2014 |
20140287513 | TRICHOPLUSIA NI PIGGYBAC TRANSPOSASES WITH REDUCED INTEGRATION ACTIVITY - The present invention is directed to nucleic acid and amino acid sequences of a novel piggyBac transposase enzymes created by modifying the transposase of | 09-25-2014 |
20140342458 | RNA-Guided Human Genome Engineering - A method of altering a eukaryotic cell is provided including transfecting the eukaryotic cell with a nucleic acid encoding RNA complementary to genomic DNA of the eukaryotic cell, transfecting the eukaryotic cell with a nucleic acid encoding an enzyme that interacts with the RNA and cleaves the genomic DNA in a site specific manner, wherein the cell expresses the RNA and the enzyme, the RNA binds to complementary genomic DNA and the enzyme cleaves the genomic DNA in a site specific manner. | 11-20-2014 |
20140349405 | RNA-DIRECTED DNA CLEAVAGE AND GENE EDITING BY CAS9 ENZYME FROM NEISSERIA MENINGITIDIS - Disclosed are components and methods for RNA-directed DNA cleavage and gene editing. The components include and the methods utilize a Cas9 protein from | 11-27-2014 |
20140356960 | Nucleic acids for cloning and expressing multiprotein complexes - The present invention relates to a nucleic acid containing at least one homing endonuclease site (HE) and at least one restriction enzyme site (X) wherein the HE and X sites are selected such that HE and X result in compatible cohesive ends when cut by the homing endonuclease and restriction enzyme, respectively, and the ligation product of HE and X cohesive ends can neither be cleaved by the homing endonuclease nor by the restriction enzyme. Further subject-matter of the present invention relates to a vector comprising the nucleic acid of the present invention, host cells containing the nucleic acid and/or the vector; a kit for cloning and/or expression of multiprotein complexes making use of the vector and the host cells, a method for producing a vector containing multiple expression cassettes, and a method for producing multiprotein complexes. The invention also relates to a methods of assembling multiple single vectors (“vector entities”) into fusion vectors and to method of disassembling a fusion vector containing multiple of such vector entities into single vectors. The invention is also directed to fusion vectors containing multiple vector entities. | 12-04-2014 |
20150017728 | MONOMER ARCHITECTURE OF TAL NUCLEASE OR ZINC FINGER NUCLEASE FOR DNA MODIFICATION - The present invention provides compositions and methods for targeted cleavage of cellular chromatin in a region of interest and/or homologous recombination at a predetermined site in cells. Compositions include fusion polypeptides comprising a TAL effector binding or a zinc finger domain and an I-TevI homing endonuclease cleavage domain as well as nucleic acid sequence encoding the same. The use of the I-TevI domain allows for monomer endonuclease sequences to achieve cleavage of cellular chromatin and represents an advantage over prior endonucleases which require self-dimerization, and two nucleases with appropriate spacers. | 01-15-2015 |
20150024499 | MODIFIED CASCADE RIBONUCLEOPROTEINS AND USES THEREOF - A clustered regularly interspaced short palindromic repeat (CRISPR)-associated complex for adaptive antiviral defence (Cascade); the Cascade protein complex comprising at least CRISPR-associated protein subunits Cas7, Cas5 and Cas6 which includes at least one subunit with an additional amino acid sequence possessing nucleic acid or chromatin modifying, visualising, transcription activating or transcription repressing activity. The Cascade complex with additional activity is combined with an RNA molecule to produce a ribonucleoprotein complex. The RNA molecule is selected to have substantial complementarity to a target sequence. Targeted ribonucleoproteins can be used as genetic engineering tools for precise cutting of nucleic acids in homologous recombination, non-homologous end joining, gene modification, gene integration, mutation repair or for their visualisation, transcriptional activation or repression. A pair of ribonucleotides fused to FokI dimers may be used to generate double-strand breakages in the DNA to facilitate these applications in a sequence-specific manner. | 01-22-2015 |
20150024500 | METHODS AND COMPOSITIONS FOR PRODUCING DOUBLE ALLELE KNOCK OUTS - The present invention provides a method and compositions utilizing the CRISPR system to disrupt a target gene in eukaryotic cells to produce double allele knock outs. The method finds use in producing afucosylated antibodies with enhanced ADCC activity. | 01-22-2015 |
20150031132 | Genome Engineering - Methods of genome engineering in cells using a TALEN lacking repeat sequences or Cas9 is provided. | 01-29-2015 |
20150031133 | Genome Engineering - Methods of genome engineering in cells using a TALEN lacking repeat sequences or Cas9 is provided. | 01-29-2015 |
20150037892 | RECOMBINATION SYSTEM - The present invention relates to a method for carrying out recombination at a target locus. | 02-05-2015 |
20150044772 | CRISPR/CAS SYSTEM-BASED NOVEL FUSION PROTEIN AND ITS APPLICATIONS IN GENOME EDITING - An inactive CRISPR/Cas system-based fusion protein and its applications in gene editing are disclosed. More particularly, chimeric fusion proteins including an inCas fused to a DNA modifying enzyme and methods of using the chimeric fusion proteins in gene editing are disclosed. The methods can be used to induce double-strand breaks and single-strand nicks in target DNAs, to generate gene disruptions, deletions, point mutations, gene replacements, insertions, inversions and other modifications of a genomic DNA within cells and organisms. | 02-12-2015 |
20150050739 | RECOMBINATION SYSTEM - The present invention relates to a method for carrying out recombination at a target locus. | 02-19-2015 |
20150056705 | METHODS AND COMPOSITIONS FOR TREATMENT OF A GENETIC CONDITION - Methods and compositions for genetic alteration of cells are provided. | 02-26-2015 |
20150064789 | COMPOSITIONS FOR LINKING DNA-BINDING DOMAINS AND CLEAVAGE DOMAINS - Disclosed herein are compositions for linking DNA binding domains and cleavage domains (or cleavage half-domains) to form non-naturally occurring nucleases. Also described are methods of making and using compositions comprising these linkers. | 03-05-2015 |
20150079680 | METHODS, CELLS & ORGANISMS - The invention relates to an approach for introducing one or more desired insertions and/or deletions of known sizes into one or more predefined locations in a nucleic acid (eg, in a cell or organism genome). They developed techniques to do this either in a sequential fashion or by inserting a discrete DNA fragment of defined size into the genome precisely in a predefined location or carrying out a discrete deletion of a defined size at a precise location. The technique is based on the observation that DNA single-stranded breaks are preferentially repaired through the HDR pathway, and this reduces the chances of indels (eg, produced by NHEJ) in the present invention and thus is more efficient than prior art techniques. The invention also provides sequential insertion and/or deletions using single- or double-stranded DNA cutting. | 03-19-2015 |
20150079681 | CRISPR-CAS COMPONENT SYSTEMS, METHODS AND COMPOSITIONS FOR SEQUENCE MANIPULATION - The invention provides for systems, methods, and compositions for manipulation of sequences and/or activities of target sequences. Provided are vectors and vector systems, some of which encode one or more components of a CRISPR complex, as well as methods for the design and use of such vectors. Also provided are methods of directing CRISPR complex formation in eukaryotic cells and methods for selecting specific cells by introducing precise mutations utilizing the CRISPR/Cas system. | 03-19-2015 |
20150118755 | REPROGRAMMING OF SOMATIC CELLS - The disclosure relates to a method of reprogramming one or more somatic cells, e.g., partially differentiated or fully/terminally differentiated somatic cells, to a less differentiated state, e.g., a pluripotent or multipotent state. In further embodiments the invention also relates to reprogrammed somatic cells produced by methods of the invention, to uses of said cells, and to methods for identifying agents useful for reprogramming somatic cells. | 04-30-2015 |
20150125958 | METHODS FOR CONTROLLING STEM CELL DIFFERENTIATION - Disclosed herein are methods for controlling stem cell differentiation through the introduction of transgenes having Xic, Tsix, or Xite sequences to block differentiation and the removal of the transgenes to allow differentiation. Also disclosed are small RNA molecules and methods for using the small RNA molecules to control stem cell differentiation. Also disclosed are stem cells genetically modified by the introduction of Xic, Tsix, or Xite sequences. | 05-07-2015 |
20150140664 | Large Gene Excision and Insertion - Methods of simultaneously excising large nucleic acid sequences from a target nucleic acid and inserting large foreign nucleic sequences into the target nucleic acid sequence using DNA binding protein nucleases are described. | 05-21-2015 |
20150140665 | Site-Specific Integration of Transgenes into Human Cells - Methods for inserting a polynucleotide sequence into the genome of a human cell are provided. The present methods result in insertion of a polynucleotide sequence of interest into the H11 locus in the genome of a human cell. Also provided are nucleic acids that include sequences for integrating a polynucleotide sequence of interest into the H11 locus in the genome of a human cell. A transgenic human cell including site specific recombination sites at the H11 locus is also disclosed. | 05-21-2015 |
20150291951 | GENOME EDITING - This document provides materials and methods for editing a genome (e.g., an animal genome in vivo). For example, methods and materials for using a targeted endonuclease and a donor nucleic acid having a length within a particular range (e.g., from 20 to 95 nucleotides) to edit a genome are provided. | 10-15-2015 |
20150322457 | COMPOSITION FOR CLEAVING A TARGET DNA COMPRISING A GUIDE RNA SPECIFIC FOR THE TARGET DNA AND CAS PROTEIN-ENCODING NUCLEIC ACID OR CAS PROTEIN, AND USE THEREOF - The present invention relates to targeted genome editing in eukaryotic cells or organisms. More particularly, the present invention relates to a composition for cleaving a target DNA in eukaryotic cells or organisms comprising a guide RNA specific for the target DNA and Cas protein-encoding nucleic acid or Cas protein, and use thereof. | 11-12-2015 |
20150329875 | METHODS AND COMPOSITIONS FOR PREVENTION OR TREATMENT OF A DISEASE - Methods and compositions for treatment of a genetic disease are provided. | 11-19-2015 |
20150344912 | COMPOSITION FOR CLEAVING A TARGET DNA COMPRISING A GUIDE RNA SPECIFIC FOR THE TARGET DNA AND CAS PROTEIN-ENCODING NUCLEIC ACID OR CAS PROTEIN, AND USE THEREOF - The present invention relates to targeted genome editing in eukaryotic cells or organisms. More particularly, the present invention relates to a composition for cleaving a target DNA in eukaryotic cells or organisms comprising a guide RNA specific for the target DNA and Cas protein-encoding nucleic acid or Cas protein, and use thereof. | 12-03-2015 |
20160002670 | RNA-Guided Human Genome Engineering - A method of altering a eukaryotic cell is provided including transfecting the eukaryotic cell with a nucleic acid encoding RNA complementary to genomic DNA of the eukaryotic cell, transfecting the eukaryotic cell with a nucleic acid encoding an enzyme that interacts with the RNA and cleaves the genomic DNA in a site specific manner, wherein the cell expresses the RNA and the enzyme, the RNA binds to complementary genomic DNA and the enzyme cleaves the genomic DNA in a site specific manner. | 01-07-2016 |
20160017366 | CRISPR-BASED GENOME MODIFICATION AND REGULATION - The present invention provides RNA-guided endonucleases, which are engineered for expression in eukaryotic cells or embryos, and methods of using the RNA-guided endonuclease for targeted genome modification in eukaryotic cells or embryos. Also provided are fusion proteins, wherein each fusion protein comprises a CRISPR/Cas-like protein or fragment thereof and an effector domain. The effector domain can be a cleavage domain, an epigenetic modification domain, a transcriptional activation domain, or a transcriptional repressor domain. Also provided are methods for using the fusion proteins to modify a chromosomal sequence or regulate expression of a chromosomal sequence. | 01-21-2016 |
20160017372 | METHODS AND PRODUCTS FOR PRODUCING ENGINEERED MAMMALIAN CELL LINES WITH AMPLIFIED TRANSGENES - Methods of inserting genes into defined locations in the chromosomal DNA of cultured mammalian cell lines which are subject to gene amplification are disclosed. In particular, sequences of interest (e.g., genes encoding biotherapeutic proteins) are inserted proximal to selectable genes in amplifiable loci, and the transformed cells are subjected to selection to induce co-amplification of the selectable gene and the sequence of interest. The invention also relates to meganucleases, vectors and engineered cell lines necessary for performing the methods, to cell lines resulting from the application of the methods, and use of the cell lines to produce protein products of interest. | 01-21-2016 |
20160024524 | Increasing Specificity for RNA-Guided Genome Editing - Methods for increasing specificity of RNA-guided genome editing, e.g., editing using CRISPR/Cas9 systems. | 01-28-2016 |
20160032274 | RNA-Guided Human Genome Engineering - A method of altering a eukaryotic cell is provided including transfecting the eukaryotic cell with a nucleic acid encoding RNA complementary to genomic DNA of the eukaryotic cell, transfecting the eukaryotic cell with a nucleic acid encoding an enzyme that interacts with the RNA and cleaves the genomic DNA in a site specific manner, wherein the cell expresses the RNA and the enzyme, the RNA binds to complementary genomic DNA and the enzyme cleaves the genomic DNA in a site specific manner. | 02-04-2016 |
20160032321 | METHODS OF NUCLEASE-BASED GENETIC ENGINEERING - The present invention relates to genetic techniques employing the direct ligatation of an external DNA fragment generated in situ by the same ZFNs that target the genome. ObLiGaRe, i.e., the obligated ligation-gated recombination, is a new method for genetic engineering using custom designed nucleases, and a strategy of site-specific gene insertion utilizing the NHEJ pathway. It applies a similar logic to the one used in unidirectional loxP sites(Oberdoerffer et al., 2003) but maintains all the advantages and flexibility of CDNs. | 02-04-2016 |
20160040189 | CIS-BLOCKED GUIDE RNA - This invention discloses reagents and methods for increasing specificity and efficiency of RNA-guided genome editing. | 02-11-2016 |
20160046963 | COMPOSITIONS AND METHODS OF NUCLEIC ACID-TARGETING NUCLEIC ACIDS - This disclosure provides for compositions and methods for the use of nucleic acid-targeting nucleic acids and complexes thereof. | 02-18-2016 |
20160060653 | METHODS AND COMPOSITIONS FOR RNA-DIRECTED TARGET DNA MODIFICATION AND FOR RNA-DIRECTED MODULATION OF TRANSCRIPTION - The present disclosure provides a DNA-targeting RNA that comprises a targeting sequence and, together with a modifying polypeptide, provides for site-specific modification of a target DNA and/or a polypeptide associated with the target DNA. The present disclosure further provides site-specific modifying polypeptides. The present disclosure further provides methods of site-specific modification of a target DNA and/or a polypeptide associated with the target DNA The present disclosure provides methods of modulating transcription of a target nucleic acid in a target cell, generally involving contacting the target nucleic acid with an enzymatically inactive Cas9 polypeptide and a DNA-targeting RNA. Kits and compositions for carrying out the methods are also provided. The present disclosure provides genetically modified cells that produce Cas9; and Cas9 transgenic non-human multicellular organisms. | 03-03-2016 |
20160060657 | METHODS AND COMPOSITIONS FOR THE TARGETED MODIFICATION OF A GENOME - Compositions and methods are provided for modifying a genomic locus of interest in a eukaryotic cell, a mammalian cell, a human cell or a non-human mammalian cell using a large targeting vector (LTVEC) comprising various endogenous or exogenous nucleic acid sequences as described herein. Further methods combine the use of the LTVEC with a CRISPR/Cas system. Compositions and methods for generating a genetically modified non-human animal comprising one or more targeted genetic modifications in their germline are also provided. | 03-03-2016 |
20160083746 | METHODS AND COMPOSITIONS FOR TARGETED GENE MODIFICATION - Disclosed herein are methods and compositions for gene targeting utilizing fusion molecules comprising a recombinase domain and a sequence-specific DNA-binding domain. | 03-24-2016 |
20160090607 | METHODS AND COMPOSITIONS FOR TREATMENT OF A GENETIC CONDITION - Methods and compositions comprising single guide RNAs targeted to endogenous gene for genetic alteration of cells are provided. | 03-31-2016 |
20160097059 | ENHANCED EXPRESSION AND STABILITY REGIONS - Expression-enhancing nucleotide sequences for expression in eukaryotic systems are provided that allow for enhanced and stable expression of recombinant proteins in eukaryotic cells. Enhanced expression and stability regions (EESYRs) are provided for expression of a gene of interest in a eukaryotic cell. Chromosomal loci, sequences, and vectors are provided for enhanced and stable expression of genes in eukaryotic cells. | 04-07-2016 |
20160102319 | CMP-ACETYLNEURAMINIC ACID HYDROXYLASE TARGETING VECTOR, TRANSGENIC ANIMAL FOR XENOTRANSPLANTATION INTRODUCED WITH THE VECTOR, AND METHOD OF MANUFACTURING THE SAME - There is provided a CMP-acetylneuraminic acid hydroxylase targeting vector, a transgenic animal for xenotransplantation introduced with the vector, and a method of manufacturing the same. The targeting vector and the cell line for transformation prepared by the present invention can be used for the efficient production of cloned pigs for xenotransplantation by the complex regulation of the expression of the genes involved in the immunological rejection responses. | 04-14-2016 |
20160102322 | CRISPR OLIGONUCLEOTIDES AND GENE EDITING - The present disclosure generally relates to compositions and methods for the genetic modification of cells. In particular, the disclosure relates to CRISPR reagents and the use of such reagents. | 04-14-2016 |
20160130608 | METHODS AND COMPOSITIONS FOR RNA-DIRECTED TARGET DNA MODIFICATION AND FOR RNA-DIRECTED MODULATION OF TRANSCRIPTION - The present disclosure provides a DNA-targeting RNA that comprises a targeting sequence and, together with a modifying polypeptide, provides for site-specific modification of a target DNA and/or a polypeptide associated with the target DNA. The present disclosure further provides site-specific modifying polypeptides. The present disclosure further provides methods of site-specific modification of a target DNA and/or a polypeptide associated with the target DNA The present disclosure provides methods of modulating transcription of a target nucleic acid in a target cell, generally involving contacting the target nucleic acid with an enzymatically inactive Cas9 polypeptide and a DNA-targeting RNA. Kits and compositions for carrying out the methods are also provided. The present disclosure provides genetically modified cells that produce Cas9; and Cas9 transgenic non-human multicellular organisms. | 05-12-2016 |
20160130609 | METHODS AND COMPOSITIONS FOR RNA-DIRECTED TARGET DNA MODIFICATION AND FOR RNA-DIRECTED MODULATION OF TRANSCRIPTION - The present disclosure provides a DNA-targeting RNA that comprises a targeting sequence and, together with a modifying polypeptide, provides for site-specific modification of a target DNA and/or a polypeptide associated with the target DNA. The present disclosure further provides site-specific modifying polypeptides. The present disclosure further provides methods of site-specific modification of a target DNA and/or a polypeptide associated with the target DNA. The present disclosure provides methods of modulating transcription of a target nucleic acid in a target cell, generally involving contacting the target nucleic acid with an enzymatically inactive Cas9 polypeptide and a DNA-targeting RNA. Kits and compositions for carrying out the methods are also provided. The present disclosure provides genetically modified cells that produce Cas9; and Cas9 transgenic non-human multicellular organisms. | 05-12-2016 |
20160153003 | Using RNA-guided FokI Nucleases (RFNs) to Increase Specificity for RNA-Guided Genome Editing | 06-02-2016 |
20160168592 | Multiplex RNA-Guided Genome Engineering | 06-16-2016 |
20160168593 | METHODS AND COMPOSITIONS FOR ENHANCING TARGETED TRANSGENE INTEGRATION | 06-16-2016 |
20160177340 | Methods, Cells & Organisms | 06-23-2016 |
20160376610 | CELL CYCLE DEPENDENT GENOME REGULATION AND MODIFICATION - Fusion protein comprising a programmable DNA modification protein and a cell cycle regulated protein, and methods of using the fusion protein to modify chromosomal sequences and/or regulate gene expression in a cell cycle dependent manner. | 12-29-2016 |
20170233765 | NON-DISRUPTIVE GENE TARGETING | 08-17-2017 |
20190144852 | Combinatorial Metabolic Engineering Using a CRISPR System | 05-16-2019 |