SG11201703747RA - METHODS AND COMPOSITIONS FOR TARGETED GENETIC MODIFICATION USING PAIRED GUIDE RNAs - Google Patents

METHODS AND COMPOSITIONS FOR TARGETED GENETIC MODIFICATION USING PAIRED GUIDE RNAs

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Publication number
SG11201703747RA
SG11201703747RA SG11201703747RA SG11201703747RA SG11201703747RA SG 11201703747R A SG11201703747R A SG 11201703747RA SG 11201703747R A SG11201703747R A SG 11201703747RA SG 11201703747R A SG11201703747R A SG 11201703747RA SG 11201703747R A SG11201703747R A SG 11201703747RA
Authority
SG
Singapore
Prior art keywords
compositions
methods
genetic modification
guide rnas
targeted genetic
Prior art date
Application number
SG11201703747RA
Inventor
Andrew J Murphy
David Frendewey
Ka-Man Venus Lai
Wojtek Auerbach
Gustavo Droguett
Anthony Gagliardi
David M Valenzuela
Vera Voronina
Lynn Macdonald
George D Yancopoulos
Original Assignee
Regeneron Pharma
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Regeneron Pharma filed Critical Regeneron Pharma
Publication of SG11201703747RA publication Critical patent/SG11201703747RA/en

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    • C12N15/09Recombinant DNA-technology
    • C12N15/87Introduction of foreign genetic material using processes not otherwise provided for, e.g. co-transformation
    • C12N15/90Stable introduction of foreign DNA into chromosome
    • C12N15/902Stable introduction of foreign DNA into chromosome using homologous recombination
    • C12N15/907Stable introduction of foreign DNA into chromosome using homologous recombination in mammalian cells
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    • C12N15/63Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
    • C12N15/79Vectors or expression systems specially adapted for eukaryotic hosts
    • C12N15/85Vectors or expression systems specially adapted for eukaryotic hosts for animal cells
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    • A01AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
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    • C12N2310/00Structure or type of the nucleic acid
    • C12N2310/10Type of nucleic acid
    • C12N2310/20Type of nucleic acid involving clustered regularly interspaced short palindromic repeats [CRISPRs]
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    • C12Q2537/00Reactions characterised by the reaction format or use of a specific feature
    • C12Q2537/10Reactions characterised by the reaction format or use of a specific feature the purpose or use of
    • C12Q2537/16Assays for determining copy number or wherein the copy number is of special importance

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  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
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SG11201703747RA 2014-11-21 2015-11-20 METHODS AND COMPOSITIONS FOR TARGETED GENETIC MODIFICATION USING PAIRED GUIDE RNAs SG11201703747RA (en)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US201462083005P 2014-11-21 2014-11-21
US201562182314P 2015-06-19 2015-06-19
US201562211421P 2015-08-28 2015-08-28
PCT/US2015/062023 WO2016081923A2 (en) 2014-11-21 2015-11-20 METHODS AND COMPOSITIONS FOR TARGETED GENETIC MODIFICATION USING PAIRED GUIDE RNAs

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SG11201703747RA true SG11201703747RA (en) 2017-06-29

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SG11201703747RA SG11201703747RA (en) 2014-11-21 2015-11-20 METHODS AND COMPOSITIONS FOR TARGETED GENETIC MODIFICATION USING PAIRED GUIDE RNAs
SG10201913829YA SG10201913829YA (en) 2014-11-21 2015-11-20 METHODS AND COMPOSITIONS FOR TARGETED GENETIC MODIFICATION USING PAIRED GUIDE RNAs

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US (4) US10457960B2 (en)
EP (2) EP3521437A1 (en)
JP (2) JP6727199B2 (en)
KR (3) KR20230070319A (en)
CN (2) CN107208078B (en)
AU (2) AU2015349692B2 (en)
BR (1) BR112017010547A2 (en)
CA (2) CA2968440A1 (en)
CY (1) CY1121738T1 (en)
DK (1) DK3221457T3 (en)
ES (1) ES2731437T3 (en)
HR (1) HRP20190949T1 (en)
HU (1) HUE044907T2 (en)
IL (3) IL283585B2 (en)
LT (1) LT3221457T (en)
MX (2) MX2017006670A (en)
NZ (1) NZ731962A (en)
PL (1) PL3221457T3 (en)
PT (1) PT3221457T (en)
RS (1) RS58893B1 (en)
RU (2) RU2020134412A (en)
SG (2) SG11201703747RA (en)
SI (1) SI3221457T1 (en)
WO (1) WO2016081923A2 (en)

Families Citing this family (111)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20050144655A1 (en) 2000-10-31 2005-06-30 Economides Aris N. Methods of modifying eukaryotic cells
US6596541B2 (en) 2000-10-31 2003-07-22 Regeneron Pharmaceuticals, Inc. Methods of modifying eukaryotic cells
WO2004106375A1 (en) 2003-05-30 2004-12-09 Merus Biopharmaceuticals B.V. I.O. Fab library for the preparation of anti vegf and anti rabies virus fabs
US20100069614A1 (en) 2008-06-27 2010-03-18 Merus B.V. Antibody producing non-human mammals
EP3613852A3 (en) 2011-07-22 2020-04-22 President and Fellows of Harvard College Evaluation and improvement of nuclease cleavage specificity
WO2013163628A2 (en) 2012-04-27 2013-10-31 Duke University Genetic correction of mutated genes
ES2904803T3 (en) 2013-02-20 2022-04-06 Regeneron Pharma Genetic modification of rats
PT3456831T (en) 2013-04-16 2021-09-10 Regeneron Pharma Targeted modification of rat genome
US9163284B2 (en) 2013-08-09 2015-10-20 President And Fellows Of Harvard College Methods for identifying a target site of a Cas9 nuclease
US9359599B2 (en) 2013-08-22 2016-06-07 President And Fellows Of Harvard College Engineered transcription activator-like effector (TALE) domains and uses thereof
US9737604B2 (en) 2013-09-06 2017-08-22 President And Fellows Of Harvard College Use of cationic lipids to deliver CAS9
US9388430B2 (en) 2013-09-06 2016-07-12 President And Fellows Of Harvard College Cas9-recombinase fusion proteins and uses thereof
US9340800B2 (en) 2013-09-06 2016-05-17 President And Fellows Of Harvard College Extended DNA-sensing GRNAS
CN106459995B (en) 2013-11-07 2020-02-21 爱迪塔斯医药有限公司 CRISPR-associated methods and compositions using dominant grnas
CN105980568B (en) 2013-12-11 2019-12-03 瑞泽恩制药公司 Method and composition for targeting modification genome
US20150166984A1 (en) 2013-12-12 2015-06-18 President And Fellows Of Harvard College Methods for correcting alpha-antitrypsin point mutations
LT3152312T (en) 2014-06-06 2020-04-27 Regeneron Pharmaceuticals, Inc. Methods and compositions for modifying a targeted locus
RU2771532C2 (en) 2014-06-26 2022-05-05 Регенерон Фармасьютикалз, Инк. Methods and compositions for targeted genetic modifications and their application methods
WO2016022363A2 (en) 2014-07-30 2016-02-11 President And Fellows Of Harvard College Cas9 proteins including ligand-dependent inteins
SG11201702309RA (en) 2014-10-15 2017-04-27 Regeneron Pharma Methods and compositions for generating or maintaining pluripotent cells
CA2963820A1 (en) 2014-11-07 2016-05-12 Editas Medicine, Inc. Methods for improving crispr/cas-mediated genome-editing
KR20230070319A (en) 2014-11-21 2023-05-22 리제너론 파마슈티칼스 인코포레이티드 METHODS AND COMPOSITIONS FOR TARGETED GENETIC MODIFICATION USING PAIRED GUIDE RNAs
BR112017013104A2 (en) 2014-12-19 2018-05-15 Regeneron Pharma methods for modifying a target genomic locus in a cell, for enhancing homologous recombination at a target genomic locus in a cell, and for producing an f0 generation from a nonhuman animal.
WO2016182959A1 (en) 2015-05-11 2016-11-17 Editas Medicine, Inc. Optimized crispr/cas9 systems and methods for gene editing in stem cells
EP3302048B1 (en) 2015-05-29 2020-02-19 Regeneron Pharmaceuticals, Inc. Non-human animals having a disruption in a c9orf72 locus
CN108026526B (en) 2015-06-09 2023-05-12 爱迪塔斯医药公司 CRISPR/CAS related methods and compositions for improving transplantation
CA2992580C (en) 2015-07-15 2022-09-20 Rutgers, The State University Of New Jersey Nuclease-independent targeted gene editing platform and uses thereof
EP3786294A1 (en) 2015-09-24 2021-03-03 Editas Medicine, Inc. Use of exonucleases to improve crispr/cas-mediated genome editing
EP4089175A1 (en) 2015-10-13 2022-11-16 Duke University Genome engineering with type i crispr systems in eukaryotic cells
IL258821B (en) 2015-10-23 2022-07-01 Harvard College Nucleobase editors and uses thereof
EP3370513A1 (en) * 2015-11-06 2018-09-12 The Jackson Laboratory Large genomic dna knock-in and uses thereof
KR102482103B1 (en) 2016-01-13 2022-12-28 리제너론 파마슈티칼스 인코포레이티드 Rodents with Engineered Heavy Chain Diversity Regions
JP6998313B2 (en) * 2016-02-11 2022-02-04 ザ リージェンツ オブ ザ ユニバーシティ オブ カリフォルニア Methods and Compositions for Modifying Mutant Dystrophin Genes in Cellular Genome
US11597924B2 (en) 2016-03-25 2023-03-07 Editas Medicine, Inc. Genome editing systems comprising repair-modulating enzyme molecules and methods of their use
EP3443086B1 (en) 2016-04-13 2021-11-24 Editas Medicine, Inc. Cas9 fusion molecules, gene editing systems, and methods of use thereof
WO2017201476A1 (en) * 2016-05-20 2017-11-23 Regeneron Pharmaceuticals, Inc. Methods for breaking immunological tolerance using multiple guide rnas
US20210010022A1 (en) * 2016-05-27 2021-01-14 Cambridge Enterprise Limited Novel nucleic acid construct
US20190323038A1 (en) * 2016-06-17 2019-10-24 Montana State Univesity Bidirectional targeting for genome editing
WO2017220527A1 (en) * 2016-06-20 2017-12-28 Glycotope Gmbh Means and methods for modifying multiple alleles
EP3476865B1 (en) * 2016-06-28 2023-09-13 Biocytogen Pharmaceuticals (Beijing) Co., Ltd. Method for constructing pd-1 gene-modified humanized animal model and use thereof
EP4219462A1 (en) 2016-07-13 2023-08-02 Vertex Pharmaceuticals Incorporated Methods, compositions and kits for increasing genome editing efficiency
EP3491130B1 (en) * 2016-07-28 2022-07-27 DSM IP Assets B.V. An assembly system for a eukaryotic cell
WO2018023014A1 (en) 2016-07-29 2018-02-01 Regeneron Pharmaceuticals, Inc. Mice comprising mutations resulting in expression of c-truncated fibrillin-1
SG11201900907YA (en) 2016-08-03 2019-02-27 Harvard College Adenosine nucleobase editors and uses thereof
US11661590B2 (en) 2016-08-09 2023-05-30 President And Fellows Of Harvard College Programmable CAS9-recombinase fusion proteins and uses thereof
US11542509B2 (en) 2016-08-24 2023-01-03 President And Fellows Of Harvard College Incorporation of unnatural amino acids into proteins using base editing
SG10202102997UA (en) 2016-09-30 2021-04-29 Regeneron Pharma Non-human animals having a hexanucleotide repeat expansion in a c9orf72 locus
GB2573062A (en) 2016-10-14 2019-10-23 Harvard College AAV delivery of nucleobase editors
LT3407709T (en) 2016-11-04 2020-10-12 Regeneron Pharmaceuticals, Inc. Non-human animals having an engineered immunoglobulin lambda light chain locus
CN106520831B (en) * 2016-11-18 2020-05-26 青岛市畜牧兽医研究所 Method for modifying mammalian genome
WO2018119359A1 (en) 2016-12-23 2018-06-28 President And Fellows Of Harvard College Editing of ccr5 receptor gene to protect against hiv infection
US20190330658A1 (en) * 2017-01-05 2019-10-31 Rutgers, The State University Targeted gene editing platform independent of dna double strand break and uses thereof
CN110446781A (en) 2017-02-15 2019-11-12 蓝鸟生物公司 Donor recovery template multiple gene group editor
EP3592853A1 (en) 2017-03-09 2020-01-15 President and Fellows of Harvard College Suppression of pain by gene editing
WO2018165629A1 (en) 2017-03-10 2018-09-13 President And Fellows Of Harvard College Cytosine to guanine base editor
CA3057192A1 (en) 2017-03-23 2018-09-27 President And Fellows Of Harvard College Nucleobase editors comprising nucleic acid programmable dna binding proteins
WO2018201086A1 (en) 2017-04-28 2018-11-01 Editas Medicine, Inc. Methods and systems for analyzing guide rna molecules
US11560566B2 (en) 2017-05-12 2023-01-24 President And Fellows Of Harvard College Aptazyme-embedded guide RNAs for use with CRISPR-Cas9 in genome editing and transcriptional activation
CN111132694A (en) * 2017-05-16 2020-05-08 健艾仕生物医药有限公司 Compositions and methods for treating alzheimer's disease
EP3635104A1 (en) 2017-06-09 2020-04-15 Editas Medicine, Inc. Engineered cas9 nucleases
US11696572B2 (en) 2017-06-27 2023-07-11 Regeneron Pharmaceuticals, Inc. Non-human animals comprising a humanized ASGR1 locus
EP3652312A1 (en) 2017-07-14 2020-05-20 Editas Medicine, Inc. Systems and methods for targeted integration and genome editing and detection thereof using integrated priming sites
JP2020534795A (en) 2017-07-28 2020-12-03 プレジデント アンド フェローズ オブ ハーバード カレッジ Methods and Compositions for Evolving Base Editing Factors Using Phage-Supported Continuous Evolution (PACE)
AU2018309708A1 (en) 2017-07-31 2020-02-06 Regeneron Pharmaceuticals, Inc. CRISPR reporter non-human animals and uses thereof
WO2019028032A1 (en) 2017-07-31 2019-02-07 Regeneron Pharmaceuticals, Inc. Cas-transgenic mouse embryonic stem cells and mice and uses thereof
US11319532B2 (en) 2017-08-30 2022-05-03 President And Fellows Of Harvard College High efficiency base editors comprising Gam
CN111163633B (en) 2017-09-29 2022-09-09 瑞泽恩制药公司 Non-human animals comprising humanized TTR loci and methods of use thereof
WO2019072241A1 (en) 2017-10-13 2019-04-18 Beijing Biocytogen Co., Ltd Genetically modified non-human animal with human or chimeric pd-1
US11795443B2 (en) 2017-10-16 2023-10-24 The Broad Institute, Inc. Uses of adenosine base editors
ES2911249T3 (en) 2017-11-10 2022-05-18 Regeneron Pharma Non-human animals comprising a slc30a8 mutation and methods of use
JP7361031B2 (en) 2017-11-30 2023-10-13 リジェネロン・ファーマシューティカルズ・インコーポレイテッド Non-human animals containing a humanized TRKB locus
CA3084049A1 (en) 2017-12-05 2019-06-13 Regeneron Pharmaceuticals, Inc. Non-human animals having an engineered immunoglobulin lambda light chain and uses thereof
CA3088788A1 (en) * 2018-01-17 2019-07-25 Vertex Pharmaceuticals Incorporated Dna-pk inhibitors
US11643670B2 (en) 2018-01-29 2023-05-09 Massachusetts Institute Of Technology Methods of enhancing chromosomal homologous recombination
WO2019183123A1 (en) 2018-03-19 2019-09-26 Regeneron Pharmaceuticals, Inc. Transcription modulation in animals using crispr/cas systems
EP3778888A4 (en) 2018-03-29 2022-04-13 Jichi Medical University Genome editing method, composition, cell, cell preparation, and method for producing cell preparation
WO2019213183A1 (en) * 2018-04-30 2019-11-07 The Trustees Of The University Of Pennsylvania In utero crispr-mediated therapeutic editing of genes
CN112218945A (en) * 2018-05-08 2021-01-12 国立大学法人大阪大学 Method for producing homozygous cells
JP2021523745A (en) 2018-05-16 2021-09-09 シンテゴ コーポレイション Methods and systems for guide RNA design and use
KR102617284B1 (en) 2018-06-14 2023-12-27 리제너론 파마슈티칼스 인코포레이티드 Non-human animals capable of dh-dh rearrangement in the immunoglobulin heavy chain coding sequences
WO2020047124A1 (en) * 2018-08-28 2020-03-05 Flagship Pioneering, Inc. Methods and compositions for modulating a genome
US11845958B2 (en) * 2018-09-05 2023-12-19 Wisconsin Alumni Research Foundation Genetically modified genes and cells, and methods of using same for silencing virus gene expression
JPWO2020050294A1 (en) * 2018-09-05 2021-08-30 学校法人慶應義塾 Homologous recombination efficiency enhancer and its use
JP7222075B2 (en) 2018-09-13 2023-02-14 リジェネロン・ファーマシューティカルズ・インコーポレイテッド Complement factor H gene knockout rats as a model of C3 glomerulopathy
JP7449291B2 (en) 2018-12-20 2024-03-13 リジェネロン・ファーマシューティカルズ・インコーポレイテッド Nuclease-mediated repeat expansion
WO2020191153A2 (en) 2019-03-19 2020-09-24 The Broad Institute, Inc. Methods and compositions for editing nucleotide sequences
WO2020206139A1 (en) 2019-04-04 2020-10-08 Regeneron Pharmaceuticals, Inc. Non-human animals comprising a humanized coagulation factor 12 locus
JP2022534867A (en) 2019-06-04 2022-08-04 リジェネロン・ファーマシューティカルズ・インコーポレイテッド Non-human animals containing humanized TTR loci with beta slip mutations and methods of use
AU2020289554A1 (en) 2019-06-05 2021-11-18 Regeneron Pharmaceuticals, Inc. Non-human animals having a limited lambda light chain repertoire expressed from the kappa locus and uses thereof
BR112021022722A2 (en) 2019-06-07 2022-01-04 Regeneron Pharma Non-human animal, non-human animal cell, non-human animal genome, humanized non-human animal albumin gene, targeting vector, method of evaluating the activity of a reagent, and, method of optimizing the activity of a reagent
WO2021108363A1 (en) 2019-11-25 2021-06-03 Regeneron Pharmaceuticals, Inc. Crispr/cas-mediated upregulation of humanized ttr allele
AU2021212668A1 (en) 2020-01-28 2022-08-18 Regeneron Pharmaceuticals, Inc. Non-human animals comprising a humanized PNPLA3 locus and methods of use
US20230081547A1 (en) 2020-02-07 2023-03-16 Regeneron Pharmaceuticals, Inc. Non-human animals comprising a humanized klkb1 locus and methods of use
US20210292754A1 (en) * 2020-03-16 2021-09-23 Pairwise Plants Services, Inc. Natural guide architectures and methods of making and using the same
EP4125348A1 (en) 2020-03-23 2023-02-08 Regeneron Pharmaceuticals, Inc. Non-human animals comprising a humanized ttr locus comprising a v30m mutation and methods of use
JP6867635B1 (en) * 2020-04-06 2021-04-28 株式会社Logomix Genome modification method and genome modification kit
EP4126224A1 (en) * 2020-04-27 2023-02-08 Duke University A high-throughput screening method to discover optimal grna pairs for crispr-mediated exon deletion
KR20230019843A (en) 2020-05-08 2023-02-09 더 브로드 인스티튜트, 인코퍼레이티드 Methods and compositions for simultaneous editing of both strands of a target double-stranded nucleotide sequence
WO2021263146A2 (en) 2020-06-26 2021-12-30 Regeneron Pharmaceuticals, Inc. Non-human animals comprising a humanized ace2 locus
CN112481297A (en) * 2020-11-02 2021-03-12 深圳先进技术研究院 Method for making chromosome structure variation
CN112382339A (en) * 2020-11-17 2021-02-19 中国人民解放军军事科学院军事医学研究院 Method and device for identifying zygote type gene activated ZGA gene
US20220195014A1 (en) 2020-12-23 2022-06-23 Regeneron Pharmaceuticals, Inc. Nucleic acids encoding anchor modified antibodies and uses thereof
US20220389461A1 (en) * 2021-05-26 2022-12-08 Inscripta, Inc. Crispr editing in diploid genomes
CN113832189B (en) * 2021-09-06 2022-10-21 中国人民解放军军事科学院军事医学研究院 gRNA for knocking out pig immunoglobulin heavy chain IGHG region and application thereof
JPWO2023054573A1 (en) * 2021-09-30 2023-04-06
WO2023077053A2 (en) 2021-10-28 2023-05-04 Regeneron Pharmaceuticals, Inc. Crispr/cas-related methods and compositions for knocking out c5
CA3238939A1 (en) 2021-12-08 2023-06-15 Gaurang Patel Mutant myocilin disease model and uses thereof
WO2023122506A1 (en) 2021-12-20 2023-06-29 Regeneron Pharmaceuticals, Inc. Non-human animals comprising humanized ace2 and tmprss loci
WO2023150798A1 (en) 2022-02-07 2023-08-10 Regeneron Pharmaceuticals, Inc. Compositions and methods for defining optimal treatment timeframes in lysosomal disease
WO2023154861A1 (en) 2022-02-11 2023-08-17 Regeneron Pharmaceuticals, Inc. Compositions and methods for screening 4r tau targeting agents
US20240130341A1 (en) 2022-09-29 2024-04-25 Regeneron Pharmaceuticals, Inc. Correction of hepatosteatosis in humanized liver animals through restoration of il6/il6r/gp130 signaling in human hepatocytes

Family Cites Families (181)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4516228A (en) 1983-08-25 1985-05-07 Mobil Oil Corporation Acoustic well logging device for detecting compressional and shear waves
US5830729A (en) 1996-04-18 1998-11-03 Institut Pasteur I Sce I-induced gene replacement and gene conversion in embryonic stem cells
WO1999005266A2 (en) 1997-07-26 1999-02-04 Wisconsin Alumni Research Foundation Trans-species nuclear transfer
JP2002533130A (en) 1998-12-31 2002-10-08 ザ ジェイ. デビッド グラッドストーン インスティテューツ Transgenic rodents and rodent cell lines expressing HIV co-receptors
WO2000046386A2 (en) 1999-02-03 2000-08-10 The Children's Medical Center Corporation Gene repair involving the induction of double-stranded dna cleavage at a chromosomal target site
DE60023936T2 (en) 1999-12-06 2006-05-24 Sangamo Biosciences Inc., Richmond METHODS OF USING RANDOMIZED ZINCFINGER PROTEIN LIBRARIES FOR IDENTIFYING GENERAL FUNCTIONS
JP2003534786A (en) 2000-05-31 2003-11-25 カイロン コーポレイション Compositions and methods for treating neoplastic diseases with chemotherapy and radiation sensitizers
US6596541B2 (en) 2000-10-31 2003-07-22 Regeneron Pharmaceuticals, Inc. Methods of modifying eukaryotic cells
US6586251B2 (en) 2000-10-31 2003-07-01 Regeneron Pharmaceuticals, Inc. Methods of modifying eukaryotic cells
US20050144655A1 (en) 2000-10-31 2005-06-30 Economides Aris N. Methods of modifying eukaryotic cells
US7105348B2 (en) 2000-10-31 2006-09-12 Regeneron Pharmaceuticals, Inc. Methods of modifying eukaryotic cells
AUPR451401A0 (en) 2001-04-20 2001-05-24 Monash University A method of nuclear transfer
CN100575485C (en) 2002-01-23 2009-12-30 犹他大学研究基金会 Use the directed karyomit(e) mutagenesis of Zinc finger nuclease
US7612250B2 (en) 2002-07-29 2009-11-03 Trustees Of Tufts College Nuclear transfer embryo formation method
US20030175968A1 (en) 2002-10-30 2003-09-18 Golic Kent G. Gene targeting method
KR20060002745A (en) 2003-01-13 2006-01-09 마헨드라 에스 라오 Persistent expression of candidate molecule in proliferating stem and progenitor cells for delivery of therapeutic products
DK2305221T3 (en) 2003-12-01 2015-08-24 Kudos Pharm Ltd DNA damage repair inhibitors for the treatment of cancer
PT1802193E (en) 2004-10-19 2014-06-23 Regeneron Pharma Method for generating a mouse homozygous for a genetic modification
FR2879622B1 (en) 2004-12-17 2008-02-01 Agronomique Inst Nat Rech IN VITRO PROCESS FOR THE PRODUCTION OF OOCYTES OR EGGS WITH TARGETED GENOMIC MODIFICATION
GB0615327D0 (en) 2006-03-30 2006-09-13 Univ Edinburgh Culture medium containing kinase inhibitors and uses thereof
US7910798B2 (en) 2006-03-31 2011-03-22 Medarex, Inc. Transgenic animals expressing chimeric antibodies for use in preparing human antibodies
CN101117633B (en) 2006-08-03 2011-07-20 上海交通大学附属儿童医院 Nucleus transplantation method
US7771967B2 (en) 2006-12-22 2010-08-10 The J. David Gladstone Institutes Nucleic acid encoding apolipoprotein E-I3
US8110379B2 (en) 2007-04-26 2012-02-07 Sangamo Biosciences, Inc. Targeted integration into the PPP1R12C locus
WO2008151081A1 (en) 2007-06-01 2008-12-11 Omt, Inc. Compositions and methods for inhibiting endogenous immunoglobulin genes and producing transgenic human idiotype antibodies
EP2313515B1 (en) 2008-08-22 2015-03-04 Sangamo BioSciences, Inc. Methods and compositions for targeted single-stranded cleavage and targeted integration
WO2010065123A1 (en) 2008-12-04 2010-06-10 Sangamo Biosciences, Inc. Genome editing in rats using zinc-finger nucleases
CA2770312A1 (en) 2009-08-11 2011-02-17 Sangamo Biosciences, Inc. Organisms homozygous for targeted modification
WO2011020014A1 (en) 2009-08-14 2011-02-17 Regeneron Pharmaceuticals, Inc. Promoter-regulated differentiation-dependent self-deleting cassette
EP2493288B1 (en) 2009-10-28 2015-02-18 Helmholtz Zentrum München Deutsches Forschungszentrum für Gesundheit und Umwelt (GmbH) Homologous recombination in the oocyte
DK3147362T3 (en) 2009-10-29 2019-04-08 Regeneron Pharma Multifunctional alleles
WO2011053957A2 (en) 2009-11-02 2011-05-05 Gen9, Inc. Compositions and methods for the regulation of multiple genes of interest in a cell
CA2782596A1 (en) 2009-12-01 2011-06-09 National Cancer Center Method for constructing chimeric rat using rat embryonic stem cells
EP2516652B1 (en) 2009-12-21 2014-11-05 Keygene N.V. Improved techniques for transfecting protoplasts
KR101951489B1 (en) 2010-01-22 2019-04-22 다우 아그로사이언시즈 엘엘씨 Excision of transgenes in genetically modified organisms
WO2011100058A1 (en) 2010-02-09 2011-08-18 Sangamo Biosciences, Inc. Targeted genomic modification with partially single-stranded donor molecules
CA2798988C (en) 2010-05-17 2020-03-10 Sangamo Biosciences, Inc. Tal-effector (tale) dna-binding polypeptides and uses thereof
GB201009732D0 (en) 2010-06-10 2010-07-21 Gene Bridges Gmbh Direct cloning
MY172702A (en) 2010-06-11 2019-12-10 Regeneron Pharma Production of fertile xy female animals from xy es cells
JP6050230B2 (en) 2010-07-21 2016-12-21 サンガモ バイオサイエンシーズ, インコーポレイテッド Methods and compositions for modification of HLA loci
WO2012018726A1 (en) 2010-08-02 2012-02-09 Cellectis Sa Method for increasing double-strand break-induced gene targeting
WO2012129198A1 (en) 2011-03-23 2012-09-27 Transposagen Biopharmaceuticals, Inc. Genetically modified rat models for obesity and diabetes
WO2012168307A2 (en) 2011-06-07 2012-12-13 Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt (GmbH) Improved recombination efficiency by inhibition of nhej dna repair
DK3424947T3 (en) 2011-10-28 2021-02-22 Regeneron Pharma GENOMIFIED T-CELL RECEPTOR MOUSE
US9637739B2 (en) 2012-03-20 2017-05-02 Vilnius University RNA-directed DNA cleavage by the Cas9-crRNA complex
WO2013141680A1 (en) 2012-03-20 2013-09-26 Vilnius University RNA-DIRECTED DNA CLEAVAGE BY THE Cas9-crRNA COMPLEX
EP2847335B1 (en) 2012-04-25 2018-06-27 Regeneron Pharmaceuticals, Inc. Nuclease-mediated targeting with large targeting vectors
WO2013169802A1 (en) 2012-05-07 2013-11-14 Sangamo Biosciences, Inc. Methods and compositions for nuclease-mediated targeted integration of transgenes
PE20150336A1 (en) 2012-05-25 2015-03-25 Univ California METHODS AND COMPOSITIONS FOR RNA-DIRECTED MODIFICATION OF TARGET DNA AND FOR RNA-DIRECTED MODULATION OF TRANSCRIPTION
KR20150023670A (en) 2012-06-12 2015-03-05 제넨테크, 인크. Methods and compositions for generating conditional knock-out alleles
EP3808844A1 (en) 2012-07-25 2021-04-21 The Broad Institute, Inc. Inducible dna binding proteins and genome perturbation tools and applications thereof
JP5952141B2 (en) * 2012-08-31 2016-07-13 京セラメディカル株式会社 Artificial cardiopulmonary pump drive
CN116064533A (en) 2012-10-23 2023-05-05 基因工具股份有限公司 Composition for cleaving target DNA and use thereof
KR101844123B1 (en) 2012-12-06 2018-04-02 시그마-알드리치 컴퍼니., 엘엘씨 Crispr-based genome modification and regulation
WO2014093694A1 (en) 2012-12-12 2014-06-19 The Broad Institute, Inc. Crispr-cas nickase systems, methods and compositions for sequence manipulation in eukaryotes
ES2786193T3 (en) 2012-12-12 2020-10-09 Broad Inst Inc Genetic engineering and optimization of improved enzyme systems, methods, and compositions for sequence manipulation
MX2015007550A (en) 2012-12-12 2017-02-02 Broad Inst Inc Delivery, engineering and optimization of systems, methods and compositions for sequence manipulation and therapeutic applications.
US8697359B1 (en) 2012-12-12 2014-04-15 The Broad Institute, Inc. CRISPR-Cas systems and methods for altering expression of gene products
DK2931898T3 (en) 2012-12-12 2016-06-20 Massachusetts Inst Technology CONSTRUCTION AND OPTIMIZATION OF SYSTEMS, PROCEDURES AND COMPOSITIONS FOR SEQUENCE MANIPULATION WITH FUNCTIONAL DOMAINS
EP3252160B1 (en) 2012-12-12 2020-10-28 The Broad Institute, Inc. Crispr-cas component systems, methods and compositions for sequence manipulation
RU2699523C2 (en) 2012-12-17 2019-09-05 Президент Энд Фэллоуз Оф Харвард Коллидж Rna-guided engineering of human genome
ES2705033T3 (en) * 2012-12-27 2019-03-21 Keygene Nv Method to eliminate a genetic link in a plant
WO2014127287A1 (en) 2013-02-14 2014-08-21 Massachusetts Institute Of Technology Method for in vivo tergated mutagenesis
ES2904803T3 (en) 2013-02-20 2022-04-06 Regeneron Pharma Genetic modification of rats
WO2014130955A1 (en) 2013-02-25 2014-08-28 Sangamo Biosciences, Inc. Methods and compositions for enhancing nuclease-mediated gene disruption
EP2922393B2 (en) 2013-02-27 2022-12-28 Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt (GmbH) Gene editing in the oocyte by cas9 nucleases
US10612043B2 (en) * 2013-03-09 2020-04-07 Agilent Technologies, Inc. Methods of in vivo engineering of large sequences using multiple CRISPR/cas selections of recombineering events
ES2901396T3 (en) 2013-03-14 2022-03-22 Caribou Biosciences Inc Nucleic Acid Targeting Nucleic Acid Compositions and Methods
US9234213B2 (en) 2013-03-15 2016-01-12 System Biosciences, Llc Compositions and methods directed to CRISPR/Cas genomic engineering systems
US20140273230A1 (en) 2013-03-15 2014-09-18 Sigma-Aldrich Co., Llc Crispr-based genome modification and regulation
JP6346266B2 (en) 2013-03-21 2018-06-20 サンガモ セラピューティクス, インコーポレイテッド Targeted disruption of T cell receptor genes using engineered zinc finger protein nucleases
WO2014165825A2 (en) 2013-04-04 2014-10-09 President And Fellows Of Harvard College Therapeutic uses of genome editing with crispr/cas systems
PT3456831T (en) 2013-04-16 2021-09-10 Regeneron Pharma Targeted modification of rat genome
US20160186208A1 (en) 2013-04-16 2016-06-30 Whitehead Institute For Biomedical Research Methods of Mutating, Modifying or Modulating Nucleic Acid in a Cell or Nonhuman Mammal
US20160040155A1 (en) 2013-04-16 2016-02-11 University Of Washington Through Its Center For Commercialization Activating an alternative pathway for homology-directed repair to stimulate targeted gene correction and genome engineering
EP2796558A1 (en) 2013-04-23 2014-10-29 Rheinische Friedrich-Wilhelms-Universität Bonn Improved gene targeting and nucleic acid carrier molecule, in particular for use in plants
EP2994531B1 (en) 2013-05-10 2018-03-28 Sangamo Therapeutics, Inc. Delivery methods and compositions for nuclease-mediated genome engineering
EP3004349B1 (en) 2013-05-29 2018-03-28 Cellectis S.A. A method for producing precise dna cleavage using cas9 nickase activity
US20140359795A1 (en) 2013-05-31 2014-12-04 Recombinetics, Inc. Genetic techniques for making animals with sortable sperm
US9982277B2 (en) 2013-06-11 2018-05-29 The Regents Of The University Of California Methods and compositions for target DNA modification
DK3011031T3 (en) 2013-06-17 2020-12-21 Broad Inst Inc PERFORMANCE AND APPLICATION OF CRISPR-CAS SYSTEMS, VECTORS AND COMPOSITIONS FOR LIVER TARGET DIRECTION AND THERAPY
DK3011032T3 (en) 2013-06-17 2020-01-20 Broad Inst Inc MANUFACTURING, MODIFICATION AND OPTIMIZATION OF SYSTEMS, PROCEDURES AND COMPOSITIONS FOR TARGETING AGAINST AND MODELING DISEASES AND DISORDERS IN POSTMITOTIC CELLS
EP3011035B1 (en) 2013-06-17 2020-05-13 The Broad Institute, Inc. Assay for quantitative evaluation of target site cleavage by one or more crispr-cas guide sequences
SG11201510286QA (en) 2013-06-17 2016-01-28 Broad Inst Inc Delivery, use and therapeutic applications of the crispr-cas systems and compositions for targeting disorders and diseases using viral components
KR20160034901A (en) 2013-06-17 2016-03-30 더 브로드 인스티튜트, 인코퍼레이티드 Optimized crispr-cas double nickase systems, methods and compositions for sequence manipulation
ES2777217T3 (en) 2013-06-17 2020-08-04 Broad Inst Inc Supply, modification and optimization of tandem guidance systems, methods and compositions for sequence manipulation
SG11201510297QA (en) 2013-06-19 2016-01-28 Sigma Aldrich Co Llc Targeted integration
US10011850B2 (en) 2013-06-21 2018-07-03 The General Hospital Corporation Using RNA-guided FokI Nucleases (RFNs) to increase specificity for RNA-Guided Genome Editing
WO2015006498A2 (en) 2013-07-09 2015-01-15 President And Fellows Of Harvard College Therapeutic uses of genome editing with crispr/cas systems
US11060083B2 (en) 2013-07-19 2021-07-13 Larix Bioscience Llc Methods and compositions for producing double allele knock outs
US9663782B2 (en) 2013-07-19 2017-05-30 Larix Bioscience Llc Methods and compositions for producing double allele knock outs
EP3024521B1 (en) 2013-07-24 2018-10-17 Medic Activ Vertriebs Gmbh Replacement cartridge
US11306328B2 (en) 2013-07-26 2022-04-19 President And Fellows Of Harvard College Genome engineering
LT3036327T (en) * 2013-08-22 2019-06-25 Pioneer Hi-Bred International, Inc. Genome modification using guide polynucleotide/cas endonuclease systems and methods of use
KR20160060659A (en) 2013-08-29 2016-05-30 템플 유니버시티-오브 더 커먼웰쓰 시스템 오브 하이어 에듀케이션 Methods and compositions for rna-guided treatment of hiv infection
CN105637087A (en) 2013-09-18 2016-06-01 科马布有限公司 Methods, cells and organisms
US10822606B2 (en) 2013-09-27 2020-11-03 The Regents Of The University Of California Optimized small guide RNAs and methods of use
WO2015048577A2 (en) 2013-09-27 2015-04-02 Editas Medicine, Inc. Crispr-related methods and compositions
WO2015052231A2 (en) 2013-10-08 2015-04-16 Technical University Of Denmark Multiplex editing system
AU2014337248B2 (en) 2013-10-17 2020-09-24 Sangamo Therapeutics, Inc. Delivery methods and compositions for nuclease-mediated genome engineering
JP5900942B2 (en) 2013-11-06 2016-04-06 国立大学法人広島大学 Nucleic acid insertion vector
CN106459995B (en) 2013-11-07 2020-02-21 爱迪塔斯医药有限公司 CRISPR-associated methods and compositions using dominant grnas
US10787684B2 (en) 2013-11-19 2020-09-29 President And Fellows Of Harvard College Large gene excision and insertion
US10450586B2 (en) 2013-11-28 2019-10-22 Horizon Discovery Limited Somatic haploid human cell line
CN105980568B (en) 2013-12-11 2019-12-03 瑞泽恩制药公司 Method and composition for targeting modification genome
AU2014361834B2 (en) 2013-12-12 2020-10-22 Massachusetts Institute Of Technology CRISPR-Cas systems and methods for altering expression of gene products, structural information and inducible modular Cas enzymes
JP6625055B2 (en) 2013-12-12 2020-01-08 ザ・ブロード・インスティテュート・インコーポレイテッド Compositions and methods of using the CRISPR-CAS system in nucleotide repeat disorders
DK3079725T3 (en) 2013-12-12 2020-01-20 Broad Inst Inc ADMINISTRATION, USE, AND THERAPEUTICAL APPLICATIONS OF CRISPR CAS SYSTEMS AND COMPOSITIONS FOR RETURNING
KR20160089526A (en) 2013-12-12 2016-07-27 더 브로드 인스티튜트, 인코퍼레이티드 Delivery, use and therapeutic applications of the crispr-cas systems and compositions for targeting disorders and diseases using particle delivery components
EP4219699A1 (en) 2013-12-12 2023-08-02 The Broad Institute, Inc. Engineering of systems, methods and optimized guide compositions with new architectures for sequence manipulation
CN111269902A (en) 2013-12-12 2020-06-12 布罗德研究所有限公司 Delivery and use of CRISPR-CAS systems and compositions
MX2016007797A (en) 2013-12-19 2016-09-07 Amyris Inc Methods for genomic integration.
CN106133141B (en) 2014-01-08 2021-08-20 哈佛学院董事及会员团体 RNA-guided gene driving
US10034463B2 (en) 2014-01-24 2018-07-31 Children's Medical Center Corporation High-throughput mouse model for optimizing antibody affinities
US20150291969A1 (en) 2014-01-30 2015-10-15 Chromatin, Inc. Compositions for reduced lignin content in sorghum and improving cell wall digestibility, and methods of making the same
US10233456B2 (en) 2014-01-30 2019-03-19 The Board Of Trustees Of The University Of Arkansas Method, vectors, cells, seeds and kits for stacking genes into a single genomic site
EP3957735A1 (en) 2014-03-05 2022-02-23 Editas Medicine, Inc. Crispr/cas-related methods and compositions for treating usher syndrome and retinitis pigmentosa
DK3116997T3 (en) 2014-03-10 2019-08-19 Editas Medicine Inc CRISPR / CAS-RELATED PROCEDURES AND COMPOSITIONS TO TREAT LEVER'S CONGENITAL AMAUROSIS 10 (LCA10)
EP3116533B1 (en) 2014-03-12 2020-08-12 Precision Biosciences, Inc. Dystrophin gene exon deletion using engineered nucleases
UA124375C2 (en) 2014-03-14 2021-09-08 Кібус Юс Ллс Methods and compositions for increasing efficiency of targeted gene modification using oligonucleotide-mediated gene repair
JP6815986B2 (en) 2014-03-26 2021-01-20 ユニバーシティ オブ メリーランド, カレッジ パーク Targeted genome editing in zygotes of large livestock
GB201406968D0 (en) 2014-04-17 2014-06-04 Green Biologics Ltd Deletion mutants
KR101823661B1 (en) 2014-04-24 2018-01-30 기초과학연구원 A method of selecting a nuclease target sequence for gene knockout based on microhomology
GB201407852D0 (en) 2014-05-02 2014-06-18 Iontas Ltd Preparation of libraries od protein variants expressed in eukaryotic cells and use for selecting binding molecules
EP3142706A1 (en) 2014-05-16 2017-03-22 Vrije Universiteit Brussel Genetic correction of myotonic dystrophy type 1
WO2015184262A1 (en) 2014-05-30 2015-12-03 The Board Of Trustees Of The Leland Stanford Junior University Compositions and methods of delivering treatments for latent viral infections
LT3152312T (en) 2014-06-06 2020-04-27 Regeneron Pharmaceuticals, Inc. Methods and compositions for modifying a targeted locus
ES2788426T3 (en) 2014-06-16 2020-10-21 Univ Johns Hopkins Compositions and Methods for the Expression of CRISPR Guide RNAs Using the H1 Promoter
RU2771532C2 (en) 2014-06-26 2022-05-05 Регенерон Фармасьютикалз, Инк. Methods and compositions for targeted genetic modifications and their application methods
JP7113618B2 (en) 2014-07-15 2022-08-05 ジュノー セラピューティクス インコーポレイテッド Engineered cells for adoptive cell therapy
EP3193944B1 (en) 2014-07-17 2021-04-07 University of Pittsburgh - Of the Commonwealth System of Higher Education Methods of treating cells containing fusion genes
US9944933B2 (en) 2014-07-17 2018-04-17 Georgia Tech Research Corporation Aptamer-guided gene targeting
SG11201701245QA (en) 2014-08-27 2017-03-30 Caribou Biosciences Inc Methods for increasing cas9-mediated engineering efficiency
WO2016036754A1 (en) 2014-09-02 2016-03-10 The Regents Of The University Of California Methods and compositions for rna-directed target dna modification
WO2016049024A2 (en) 2014-09-24 2016-03-31 The Broad Institute Inc. Delivery, use and therapeutic applications of the crispr-cas systems and compositions for modeling competition of multiple cancer mutations in vivo
WO2016049163A2 (en) 2014-09-24 2016-03-31 The Broad Institute Inc. Use and production of chd8+/- transgenic animals with behavioral phenotypes characteristic of autism spectrum disorder
WO2016049258A2 (en) 2014-09-25 2016-03-31 The Broad Institute Inc. Functional screening with optimized functional crispr-cas systems
JP2017534295A (en) 2014-09-29 2017-11-24 ザ ジャクソン ラボラトリー High-efficiency, high-throughput generation of genetically modified mammals by electroporation
KR102630014B1 (en) 2014-10-01 2024-01-25 더 제너럴 하스피탈 코포레이션 Methods for increasing efficiency of nuclease-induced homology-directed repair
US20180250424A1 (en) 2014-10-10 2018-09-06 Editas Medicine, Inc. Compositions and methods for promoting homology directed repair
WO2016061073A1 (en) 2014-10-14 2016-04-21 Memorial Sloan-Kettering Cancer Center Composition and method for in vivo engineering of chromosomal rearrangements
SG11201702309RA (en) 2014-10-15 2017-04-27 Regeneron Pharma Methods and compositions for generating or maintaining pluripotent cells
BR112017007923B1 (en) 2014-10-17 2023-12-12 The Penn State Research Foundation METHOD FOR PRODUCING GENETIC MANIPULATION MEDIATED BY MULTIPLEX REACTIONS WITH RNA IN A RECEIVING CELL, CONSTRUCTION OF NUCLEIC ACID, EXPRESSION CASSETTE, VECTOR, RECEIVING CELL AND GENETICALLY MODIFIED CELL
WO2016065364A1 (en) 2014-10-24 2016-04-28 Life Technologies Corporation Compositions and methods for enhancing homologous recombination
WO2016073955A2 (en) 2014-11-06 2016-05-12 President And Fellows Of Harvard College Cells lacking b2m surface expression and methods for allogeneic administration of such cells
CA2963820A1 (en) 2014-11-07 2016-05-12 Editas Medicine, Inc. Methods for improving crispr/cas-mediated genome-editing
KR20230070319A (en) 2014-11-21 2023-05-22 리제너론 파마슈티칼스 인코포레이티드 METHODS AND COMPOSITIONS FOR TARGETED GENETIC MODIFICATION USING PAIRED GUIDE RNAs
CA2968808A1 (en) 2014-11-27 2016-06-02 Danziger Innovations Ltd. Nucleic acid constructs for genome editing
WO2016089866A1 (en) 2014-12-01 2016-06-09 President And Fellows Of Harvard College Rna-guided systems for in vivo gene editing
WO2016094874A1 (en) 2014-12-12 2016-06-16 The Broad Institute Inc. Escorted and functionalized guides for crispr-cas systems
WO2016094880A1 (en) 2014-12-12 2016-06-16 The Broad Institute Inc. Delivery, use and therapeutic applications of crispr systems and compositions for genome editing as to hematopoietic stem cells (hscs)
EP3230452A1 (en) 2014-12-12 2017-10-18 The Broad Institute Inc. Dead guides for crispr transcription factors
WO2016097751A1 (en) 2014-12-18 2016-06-23 The University Of Bath Method of cas9 mediated genome engineering
BR112017013104A2 (en) 2014-12-19 2018-05-15 Regeneron Pharma methods for modifying a target genomic locus in a cell, for enhancing homologous recombination at a target genomic locus in a cell, and for producing an f0 generation from a nonhuman animal.
US10863730B2 (en) 2014-12-26 2020-12-15 Riken Gene knockout method
WO2016112242A1 (en) 2015-01-08 2016-07-14 President And Fellows Of Harvard College Split cas9 proteins
CN113388670B (en) 2015-01-09 2024-02-02 生物辐射实验室股份有限公司 Detecting genome editing
CN107429263A (en) 2015-01-15 2017-12-01 斯坦福大学托管董事会 The method of controlling gene group editor
WO2016130697A1 (en) 2015-02-11 2016-08-18 Memorial Sloan Kettering Cancer Center Methods and kits for generating vectors that co-express multiple target molecules
BR112017017812A2 (en) 2015-02-23 2018-04-10 Crispr Therapeutics Ag Materials and methods for treatment of hemoglobinopathies
GB2535532B (en) 2015-02-23 2021-05-12 Knorr Bremse Systeme Fuer Nutzfahrzeuge Gmbh Brake valve arrangement
EP3262173A2 (en) 2015-02-23 2018-01-03 Crispr Therapeutics AG Materials and methods for treatment of human genetic diseases including hemoglobinopathies
WO2016138574A1 (en) 2015-03-02 2016-09-09 Sinai Health System Homologous recombination factors
GB201504223D0 (en) 2015-03-12 2015-04-29 Genome Res Ltd Biallelic genetic modification
WO2016154579A2 (en) 2015-03-26 2016-09-29 Editas Medicine, Inc. Crispr/cas-mediated gene conversion
WO2016160721A1 (en) 2015-03-27 2016-10-06 President And Fellows Of Harvard College Modified t cells and methods of making and using the same
AU2016244033A1 (en) 2015-04-01 2017-10-19 Editas Medicine, Inc. CRISPR/CAS-related methods and compositions for treating Duchenne Muscular Dystrophy and Becker Muscular Dystrophy
US10155938B2 (en) 2015-04-14 2018-12-18 City Of Hope Coexpression of CAS9 and TREX2 for targeted mutagenesis
EP3286301B1 (en) 2015-04-22 2021-07-28 Sonic Master Limited Generation of muscle-lineage cells from stem cells
WO2016174056A1 (en) 2015-04-27 2016-11-03 Genethon Compositions and methods for the treatment of nucleotide repeat expansion disorders
DK3289080T3 (en) 2015-04-30 2021-11-08 Univ Columbia GENERATION THERAPY FOR AUTOSOMAL DOMINANT DISEASES
IL296365A (en) 2015-05-16 2022-11-01 Genzyme Corp Gene editing of deep intronic mutations
US9790490B2 (en) 2015-06-18 2017-10-17 The Broad Institute Inc. CRISPR enzymes and systems
EP3359661A4 (en) 2015-10-08 2019-05-15 President and Fellows of Harvard College Multiplexed genome editing
AU2016341041A1 (en) 2015-10-20 2018-03-15 Pioneer Hi-Bred International, Inc. Methods and compositions for marker-free genome modification
EP3370513A1 (en) 2015-11-06 2018-09-12 The Jackson Laboratory Large genomic dna knock-in and uses thereof
US11597924B2 (en) 2016-03-25 2023-03-07 Editas Medicine, Inc. Genome editing systems comprising repair-modulating enzyme molecules and methods of their use
WO2017173004A1 (en) 2016-03-30 2017-10-05 Mikuni Takayasu A method for in vivo precise genome editing
WO2017180859A1 (en) 2016-04-13 2017-10-19 University Of Massachusetts Repairing compound heterozygous recessive mutations by allele exchange
WO2017201476A1 (en) 2016-05-20 2017-11-23 Regeneron Pharmaceuticals, Inc. Methods for breaking immunological tolerance using multiple guide rnas
US11643670B2 (en) 2018-01-29 2023-05-09 Massachusetts Institute Of Technology Methods of enhancing chromosomal homologous recombination

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