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
Other languages
English (en)
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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    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • C12N15/87—Introduction of foreign genetic material using processes not otherwise provided for, e.g. co-transformation
    • C12N15/90—Stable introduction of foreign DNA into chromosome
    • C12N15/902—Stable introduction of foreign DNA into chromosome using homologous recombination
    • C12N15/907—Stable introduction of foreign DNA into chromosome using homologous recombination in mammalian cells
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
    • A01K67/00—Rearing or breeding animals, not otherwise provided for; New or modified breeds of animals
    • A01K67/027—New or modified breeds of vertebrates
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    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
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    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
    • C12N15/113—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing
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    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
    • C12N15/79—Vectors or expression systems specially adapted for eukaryotic hosts
    • C12N15/85—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells
    • C12N15/8509—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells for producing genetically modified animals, e.g. transgenic
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
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    • C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
    • C12N9/14—Hydrolases (3)
    • C12N9/16—Hydrolases (3) acting on ester bonds (3.1)
    • C12N9/22—Ribonucleases RNAses, DNAses
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    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
    • C12Q1/6813—Hybridisation assays
    • C12Q1/6827—Hybridisation assays for detection of mutation or polymorphism
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    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
    • C12Q1/6876—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
    • C12Q1/6888—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for detection or identification of organisms
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
    • A01K2217/00—Genetically modified animals
    • A01K2217/07—Animals genetically altered by homologous recombination
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
    • A01K2227/00—Animals characterised by species
    • A01K2227/10—Mammal
    • A01K2227/105—Murine
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    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/10—Type of nucleic acid
    • C12N2310/20—Type of nucleic acid involving clustered regularly interspaced short palindromic repeats [CRISPRs]
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q2537/00—Reactions characterised by the reaction format or use of a specific feature
    • C12Q2537/10—Reactions characterised by the reaction format or use of a specific feature the purpose or use of
    • C12Q2537/16—Assays for determining copy number or wherein the copy number is of special importance

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  • Life Sciences & Earth Sciences (AREA)
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  • Genetics & Genomics (AREA)
  • Engineering & Computer Science (AREA)
  • Zoology (AREA)
  • Organic Chemistry (AREA)
  • Wood Science & Technology (AREA)
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  • Bioinformatics & Cheminformatics (AREA)
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  • General Health & Medical Sciences (AREA)
  • Microbiology (AREA)
  • Biochemistry (AREA)
  • Physics & Mathematics (AREA)
  • Biophysics (AREA)
  • Plant Pathology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Analytical Chemistry (AREA)
  • Environmental Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Biodiversity & Conservation Biology (AREA)
  • Animal Husbandry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Immunology (AREA)
  • Cell Biology (AREA)
  • Mycology (AREA)
  • Crystallography & Structural Chemistry (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
  • Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicinal Preparation (AREA)
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

Publications (1)

Publication Number Publication Date
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 (es)
EP (2) EP3521437A1 (es)
JP (2) JP6727199B2 (es)
KR (3) KR102531016B1 (es)
CN (2) CN107208078B (es)
AU (2) AU2015349692B2 (es)
BR (1) BR112017010547A2 (es)
CA (2) CA2968440A1 (es)
CY (1) CY1121738T1 (es)
DK (1) DK3221457T3 (es)
ES (1) ES2731437T3 (es)
HR (1) HRP20190949T1 (es)
HU (1) HUE044907T2 (es)
IL (3) IL283585B2 (es)
LT (1) LT3221457T (es)
MX (2) MX2017006670A (es)
NZ (1) NZ731962A (es)
PL (1) PL3221457T3 (es)
PT (1) PT3221457T (es)
RS (1) RS58893B1 (es)
RU (2) RU2020134412A (es)
SG (2) SG11201703747RA (es)
SI (1) SI3221457T1 (es)
WO (1) WO2016081923A2 (es)

Families Citing this family (115)

* 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
AU2004242614B2 (en) 2003-05-30 2011-09-22 Merus N.V. 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
WO2013066438A2 (en) 2011-07-22 2013-05-10 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
CA2900992C (en) 2013-02-20 2023-02-28 Regeneron Pharmaceuticals, Inc. Genetic modification of rats
AU2014253942B9 (en) 2013-04-16 2020-08-13 Regeneron Pharmaceuticals, Inc. Targeted modification of rat genome
US20150044192A1 (en) 2013-08-09 2015-02-12 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
US9526784B2 (en) 2013-09-06 2016-12-27 President And Fellows Of Harvard College Delivery system for functional nucleases
US9340799B2 (en) 2013-09-06 2016-05-17 President And Fellows Of Harvard College MRNA-sensing switchable gRNAs
US9322037B2 (en) 2013-09-06 2016-04-26 President And Fellows Of Harvard College Cas9-FokI fusion proteins and uses thereof
JP2016536021A (ja) 2013-11-07 2016-11-24 エディタス・メディシン，インコーポレイテッド ＣＲＩＳＰＲ関連方法および支配ｇＲＮＡのある組成物
RU2725520C2 (ru) 2013-12-11 2020-07-02 Регенерон Фармасьютикалс, Инк. Способы и композиции для направленной модификации генома
US9068179B1 (en) 2013-12-12 2015-06-30 President And Fellows Of Harvard College Methods for correcting presenilin point mutations
KR102374379B1 (ko) 2014-06-06 2022-03-17 리제너론 파마슈티칼스 인코포레이티드 표적화된 좌를 변형시키는 방법 및 조성물
SG11201610633QA (en) 2014-06-26 2017-01-27 Regeneron Pharma Methods and compositions for targeted genetic modifications and methods of use
WO2016022363A2 (en) 2014-07-30 2016-02-11 President And Fellows Of Harvard College Cas9 proteins including ligand-dependent inteins
EP3561052A1 (en) 2014-10-15 2019-10-30 Regeneron Pharmaceuticals, Inc. Methods and compositions for generating or maintaining pluripotent cells
AU2015342749B2 (en) 2014-11-07 2022-01-27 Editas Medicine, Inc. Methods for improving CRISPR/Cas-mediated genome-editing
KR102531016B1 (ko) 2014-11-21 2023-05-10 리제너론 파마슈티칼스 인코포레이티드 쌍 형성된 가이드 rna를 사용하는 표적화된 유전자 변형을 위한 방법 및 조성물
CA2971213C (en) 2014-12-19 2023-09-26 Regeneron Pharmaceuticals, Inc. Methods and compositions for targeted genetic modification through single-step multiple targeting
US11390884B2 (en) 2015-05-11 2022-07-19 Editas Medicine, Inc. Optimized CRISPR/cas9 systems and methods for gene editing in stem cells
US10285388B2 (en) 2015-05-29 2019-05-14 Regeneron Pharmaceuticals, Inc. Non-human animals having a disruption in a C9ORF72 locus
KR20180031671A (ko) 2015-06-09 2018-03-28 에디타스 메디신, 인코포레이티드 이식의 개선을 위한 crispr/cas-관련 방법 및 조성물
JP7044373B2 (ja) 2015-07-15 2022-03-30 ラトガース，ザ ステート ユニバーシティ オブ ニュージャージー ヌクレアーゼ非依存的な標的化遺伝子編集プラットフォームおよびその用途
WO2017053879A1 (en) 2015-09-24 2017-03-30 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
IL294014B2 (en) 2015-10-23 2024-07-01 Harvard College Nucleobase editors and their uses
CN108471731A (zh) * 2015-11-06 2018-08-31 杰克逊实验室 大型基因组dna敲入及其用途
CA3011359A1 (en) 2016-01-13 2017-07-20 Regeneron Pharmaceuticals, Inc. Rodents having an engineered heavy chain diversity region
US11666666B2 (en) * 2016-02-11 2023-06-06 The Regents Of The University Of California Methods and compositions for modifying a mutant dystrophin gene in a cell's genome
EP3433363A1 (en) 2016-03-25 2019-01-30 Editas Medicine, Inc. Genome editing systems comprising repair-modulating enzyme molecules and methods of their use
US11236313B2 (en) 2016-04-13 2022-02-01 Editas Medicine, Inc. Cas9 fusion molecules, gene editing systems, and methods of use thereof
RU2745563C2 (ru) * 2016-05-20 2021-03-29 Регенерон Фармасьютикалс, Инк. Способы преодоления иммунологической толерантности с использованием множества направляющих рнк
US20210010022A1 (en) * 2016-05-27 2021-01-14 Cambridge Enterprise Limited Novel nucleic acid construct
WO2017219033A1 (en) * 2016-06-17 2017-12-21 Montana State University Bidirectional targeting for genome editing
EP3472338B1 (en) * 2016-06-20 2024-05-22 Octapharma AG Means and methods for modifying multiple alleles
DK3476865T5 (da) * 2016-06-28 2024-09-09 Biocytogen Pharmaceuticals Beijing Co Ltd Fremgangsmåde til konstruktion af pd-1-gen-modificeret humaniseret dyremodel og anvendelse deraf
AU2017295720B2 (en) 2016-07-13 2021-07-22 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
US10548302B2 (en) 2016-07-29 2020-02-04 Regeneron Pharmaceuticals, Inc. Fibrillin-1 mutations for modeling neonatal progeroid syndrome with congenital lipodystrophy
CA3032699A1 (en) 2016-08-03 2018-02-08 President And Fellows Of Harvard College Adenosine nucleobase editors and uses thereof
AU2017308889B2 (en) 2016-08-09 2023-11-09 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
WO2018064600A1 (en) 2016-09-30 2018-04-05 Regeneron Pharmaceuticals, Inc. Non-human animals having a hexanucleotide repeat expansion in a c9orf72 locus
WO2018071868A1 (en) 2016-10-14 2018-04-19 President And Fellows Of Harvard College Aav delivery of nucleobase editors
RU2021129958A (ru) 2016-11-04 2021-11-02 Регенерон Фармасьютикалс, Инк. Отличные от человека животные со сконструированным локусом легкой лямбда-цепи иммуноглобулина
CN106520831B (zh) * 2016-11-18 2020-05-26 青岛市畜牧兽医研究所 一种哺乳动物基因组修饰方法
US10745677B2 (en) 2016-12-23 2020-08-18 President And Fellows Of Harvard College Editing of CCR5 receptor gene to protect against HIV infection
JP7219972B2 (ja) 2017-01-05 2023-02-09 ラトガース，ザ ステート ユニバーシティ オブ ニュー ジャージー Ｄｎａ二本鎖切断に非依存的な標的化遺伝子編集プラットフォームおよびその用途
EP4095263A1 (en) 2017-01-06 2022-11-30 Editas Medicine, Inc. Methods of assessing nuclease cleavage
AU2018221730B2 (en) 2017-02-15 2024-06-20 Novo Nordisk A/S Donor repair templates multiplex genome editing
EP3592853A1 (en) 2017-03-09 2020-01-15 President and Fellows of Harvard College Suppression of pain by gene editing
JP2020510439A (ja) 2017-03-10 2020-04-09 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 シトシンからグアニンへの塩基編集因子
IL269458B2 (en) 2017-03-23 2024-02-01 Harvard College Nucleic base editors that include nucleic acid programmable DNA binding proteins
EP3615672A1 (en) 2017-04-28 2020-03-04 Editas Medicine, Inc. Methods and systems for analyzing guide rna molecules
WO2018209320A1 (en) 2017-05-12 2018-11-15 President And Fellows Of Harvard College Aptazyme-embedded guide rnas for use with crispr-cas9 in genome editing and transcriptional activation
JP2020520931A (ja) * 2017-05-16 2020-07-16 ジェネラス バイオファーマ リミティド アルツハイマー病の治療用組成物および治療方法
CN110997908A (zh) 2017-06-09 2020-04-10 爱迪塔斯医药公司 工程化的cas9核酸酶
CA3066945A1 (en) 2017-06-27 2019-01-03 Regeneron Pharmaceuticals, Inc. Non-human animals comprising a humanized asgr1 locus
US11866726B2 (en) 2017-07-14 2024-01-09 Editas Medicine, Inc. Systems and methods for targeted integration and genome editing and detection thereof using integrated priming sites
JP2020534795A (ja) 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 ファージによって支援される連続的進化（ｐａｃｅ）を用いて塩基編集因子を進化させるための方法および組成物
US11130999B2 (en) 2017-07-31 2021-09-28 Regeneron Pharmaceuticals, Inc. Cas-ready mouse embryonic stem cells and mice and uses thereof
CN111182790A (zh) 2017-07-31 2020-05-19 瑞泽恩制药公司 Crispr报告体非人类动物及其用途
US11319532B2 (en) 2017-08-30 2022-05-03 President And Fellows Of Harvard College High efficiency base editors comprising Gam
AU2018338790B2 (en) 2017-09-29 2022-09-15 Regeneron Pharmaceuticals, Inc. Non-human animals comprising a humanized TTR locus and methods of use
WO2019072241A1 (en) 2017-10-13 2019-04-18 Beijing Biocytogen Co., Ltd NON-HUMAN ANIMAL GENETICALLY MODIFIED WITH PD-1 HUMAN OR CHIMERIC
US11795443B2 (en) 2017-10-16 2023-10-24 The Broad Institute, Inc. Uses of adenosine base editors
KR102444458B1 (ko) 2017-11-10 2022-09-19 리제너론 파마슈티칼스 인코포레이티드 Slc30a8 돌연변이를 포함하는 비인간 동물 및 사용 방법
IL274740B2 (en) 2017-11-30 2024-06-01 Regeneron Pharma Non-human animals containing a human TRKB locus
BR112020011184A2 (pt) 2017-12-05 2020-11-17 Regeneron Pharmaceuticals, Inc. roedor geneticamente modificado, células de roedor isolada, célula imortalizada, embrião de roedor, uso de um roedor, célula b isolada, anticorpo preparado por um método, métodos para produzir um roedor geneticamente modificado, um anticorpo, uma cadeia pesada totalmente humana ou uma cadeia leve totalmente humana, uma sequência nucleotídica, para gerar uma ¿ sequência de domínio variável de cadeia pesada ou leve humana e gerar uma ¿ sequência da região variável de cadeia pesada ou leve humana, célula-tronco embrionária, célula es de roedor, e, célula es isolada de roedor.
WO2019143675A1 (en) * 2018-01-17 2019-07-25 Vertex Pharmaceuticals Incorporated Dna-pk inhibitors
US12005127B2 (en) 2018-01-17 2024-06-11 Vertex Pharmaceuticals Incorporated DNA-PK inhibitors
US11643670B2 (en) 2018-01-29 2023-05-09 Massachusetts Institute Of Technology Methods of enhancing chromosomal homologous recombination
CN111885915B (zh) 2018-03-19 2023-04-28 瑞泽恩制药公司 使用crispr/cas系统对动物进行转录调制
CN112534051A (zh) 2018-03-29 2021-03-19 学校法人自治医科大学 基因组编辑方法、组合物、细胞、细胞制剂、以及细胞制剂的制造方法
WO2019213183A1 (en) * 2018-04-30 2019-11-07 The Trustees Of The University Of Pennsylvania In utero crispr-mediated therapeutic editing of genes
US20210230637A1 (en) * 2018-05-08 2021-07-29 Osaka University Method for producing homozygous cells
GB2589246A (en) 2018-05-16 2021-05-26 Synthego Corp Methods and systems for guide RNA design and use
SG11202012084WA (en) 2018-06-14 2021-01-28 Regeneron Pharma Non-human animals capable of dh-dh rearrangement in the immunoglobulin heavy chain coding sequences
KR20210049859A (ko) * 2018-08-28 2021-05-06 플래그쉽 파이어니어링 이노베이션스 브이아이, 엘엘씨 게놈을 조절하는 방법 및 조성물
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 (ja) * 2018-09-05 2021-08-30 学校法人慶應義塾 相同組換え効率上昇剤及びその使用
JP7222075B2 (ja) 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 Ｃ３糸球体症のモデルとしての補体因子ｈ遺伝子ノックアウトラット
JP7250031B2 (ja) * 2018-09-25 2023-03-31 公益財団法人微生物化学研究会 新規ウイルスベクターおよびその製造方法と使用方法
WO2020131632A1 (en) 2018-12-20 2020-06-25 Regeneron Pharmaceuticals, Inc. Nuclease-mediated repeat expansion
DE112020001342T5 (de) 2019-03-19 2022-01-13 President and Fellows of Harvard College Verfahren und Zusammensetzungen zum Editing von Nukleotidsequenzen
CN114206108B (zh) 2019-04-04 2023-09-29 瑞泽恩制药公司 包括人源化凝血因子12基因座的非人动物
WO2020247452A1 (en) 2019-06-04 2020-12-10 Regeneron Pharmaceuticals, Inc. Non-human animals comprising a humanized ttr locus with a beta-slip mutation and methods of use
WO2020247623A1 (en) 2019-06-05 2020-12-10 Regeneron Pharmaceuticals, Inc. Non-human animals having a limited lambda light chain repertoire expressed from the kappa locus and uses thereof
SG11202111256XA (en) 2019-06-07 2021-11-29 Regeneron Pharma Non-human animals comprising a humanized albumin locus
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
WO2021158883A1 (en) 2020-02-07 2021-08-12 Regeneron Pharmaceuticals, Inc. Non-human animals comprising a humanized klkb1 locus and methods of use
WO2021188526A1 (en) * 2020-03-16 2021-09-23 Pairwise Plants Services, Inc. Natural guide architectures and methods of making and using the same
WO2021195079A1 (en) 2020-03-23 2021-09-30 Regeneron Pharmaceuticals, Inc. Non-human animals comprising a humanized ttr locus comprising a v30m mutation and methods of use
JP6867635B1 (ja) * 2020-04-06 2021-04-28 株式会社Ｌｏｇｏｍｉｘ ゲノム改変方法及びゲノム改変キット
JP2023515710A (ja) * 2020-04-27 2023-04-13 デューク ユニバーシティ ＣＲＩＳＰＲ媒介式エクソン欠失用の最適なｇＲＮＡ対を発見するためのハイスループットスクリーニング法
DE112021002672T5 (de) 2020-05-08 2023-04-13 President And Fellows Of Harvard College Vefahren und zusammensetzungen zum gleichzeitigen editieren beider stränge einer doppelsträngigen nukleotid-zielsequenz
EP4171215A2 (en) 2020-06-26 2023-05-03 Regeneron Pharmaceuticals, Inc. Non-human animals comprising a humanized ace2 locus
CN112481297A (zh) * 2020-11-02 2021-03-12 深圳先进技术研究院 一种制造染色体结构变异的方法
CN112382339B (zh) * 2020-11-17 2024-08-13 中国人民解放军军事科学院军事医学研究院 一种识别合子型基因激活zga基因的方法及装置
US20240317849A1 (en) 2020-12-23 2024-09-26 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 (zh) * 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 一种用于敲除猪免疫球蛋白重链IGHG区的gRNA及其应用
JPWO2023054573A1 (es) * 2021-09-30 2023-04-06
CN118251491A (zh) 2021-10-28 2024-06-25 瑞泽恩制药公司 用于敲除C5的CRISPR/Cas相关方法及组合物
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
US20230257432A1 (en) 2022-02-11 2023-08-17 Regeneron Pharmaceuticals, Inc. Compositions and methods for screening 4r tau targeting agents
WO2023250511A2 (en) 2022-06-24 2023-12-28 Tune Therapeutics, Inc. Compositions, systems, and methods for reducing low-density lipoprotein through targeted gene repression
US20240224964A9 (en) 2022-09-29 2024-07-11 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
AU2391000A (en) 1998-12-31 2000-07-31 J. David Gladstone Institutes, The Transgenic rodents and rodent cell lines expressing hiv co-receptors
JP2002535995A (ja) 1999-02-03 2002-10-29 ザ チルドレンズ メディカル センター コーポレイション 染色体標的部位での二本鎖ｄｎａ切断の誘導を含む遺伝子修復
DE60023936T2 (de) 1999-12-06 2006-05-24 Sangamo Biosciences Inc., Richmond Methoden zur verwendung von randomisierten zinkfingerprotein-bibliotheken zur identifizierung von genfunktionen
US6974867B2 (en) 2000-05-31 2005-12-13 Chiron Corporation Compositions and methods for treating neoplastic disease using chemotherapy and radiation sensitizers
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
US6596541B2 (en) 2000-10-31 2003-07-22 Regeneron Pharmaceuticals, Inc. Methods of modifying eukaryotic cells
AUPR451401A0 (en) 2001-04-20 2001-05-24 Monash University A method of nuclear transfer
EP1476547B1 (en) 2002-01-23 2006-12-06 The University of Utah Research Foundation Targeted chromosomal mutagenesis using zinc finger nucleases
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
JP2006517101A (ja) 2003-01-13 2006-07-20 エス． ラオ、マヘンドラ 治療用産物を送達するための、増殖性の幹細胞および前駆細胞における候補分子の持続的発現
TWI338000B (en) 2003-12-01 2011-03-01 Kudos Pharm Ltd Dna damage repair inhibitors for treatment of cancer
PL1802193T3 (pl) 2004-10-19 2014-09-30 Regeneron Pharma Sposób wytwarzania myszy homozygotycznej pod względem modyfikacji genetycznej
FR2879622B1 (fr) 2004-12-17 2008-02-01 Agronomique Inst Nat Rech Procede in vitro de production d'ovocytes ou d'oeufs presentant une modification genomique ciblee
GB0615327D0 (en) 2006-03-30 2006-09-13 Univ Edinburgh Culture medium containing kinase inhibitors and uses thereof
JP5514539B2 (ja) 2006-03-31 2014-06-04 メダレックス・リミテッド・ライアビリティ・カンパニー ヒト抗体の調製に用いるためのキメラ抗体を発現するトランスジェニック動物
CN101117633B (zh) 2006-08-03 2011-07-20 上海交通大学附属儿童医院 一种细胞核移植方法
US7771967B2 (en) 2006-12-22 2010-08-10 The J. David Gladstone Institutes Nucleic acid encoding apolipoprotein E-I3
DE602008003684D1 (de) 2007-04-26 2011-01-05 Sangamo Biosciences Inc Gezielte integration in die ppp1r12c-position
AU2008259939B2 (en) 2007-06-01 2014-03-13 Open Monoclonal Technology, Inc. Compositions and methods for inhibiting endogenous immunoglobulin genes and producing transgenic human idiotype antibodies
CA2734235C (en) 2008-08-22 2019-03-26 Sangamo Biosciences, Inc. Methods and compositions for targeted single-stranded cleavage and targeted integration
EP3156494B8 (en) 2008-12-04 2018-09-19 Sangamo Therapeutics, Inc. Genome editing in rats using zinc-finger nucleases
NZ619886A (en) 2009-08-11 2015-03-27 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
PT3147362T (pt) 2009-10-29 2019-04-02 Regeneron Pharma Alelos multifuncionais
WO2011053957A2 (en) 2009-11-02 2011-05-05 Gen9, Inc. Compositions and methods for the regulation of multiple genes of interest in a cell
US9309537B2 (en) 2009-12-01 2016-04-12 National Cancer Center Chimeric rat produced using rat embryonic stem cells in the presence of an ES cell differentiation suppressant
ES2583060T3 (es) 2009-12-21 2016-09-16 Keygene N.V. Técnicas mejoradas para la transfección de protoplastos
NZ600546A (en) 2010-01-22 2014-08-29 Dow Agrosciences Llc Excision of transgenes in genetically modified organisms
CA2788850C (en) 2010-02-09 2019-06-25 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
WO2011156723A1 (en) 2010-06-11 2011-12-15 Regeneron Pharmaceuticals, Inc. Production of fertile xy female animals from xy es cells
WO2012012667A2 (en) 2010-07-21 2012-01-26 Sangamo Biosciences, Inc. Methods and compositions for modification of a hla locus
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
EP2718446A2 (en) 2011-06-07 2014-04-16 Helmholtz Zentrum München Deutsches Forschungszentrum für Gesundheit und Umwelt (GmbH) Improved recombination efficiency by inhibition of nhej dna repair
CN114891797A (zh) 2011-10-28 2022-08-12 瑞泽恩制药公司 T细胞受体基因修饰小鼠
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
PL2847335T3 (pl) 2012-04-25 2019-01-31 Regeneron Pharmaceuticals, Inc. Celowanie dużymi wektorami do celowania wspomagane nukleazą
WO2013169802A1 (en) 2012-05-07 2013-11-14 Sangamo Biosciences, Inc. Methods and compositions for nuclease-mediated targeted integration of transgenes
DE202013012241U1 (de) 2012-05-25 2016-01-18 Emmanuelle Charpentier Zusammensetzungen für die durch RNA gesteuerte Modifikation einer Ziel-DNA und für die durch RNA gesteuerte Modulation der Transkription
KR20150023670A (ko) 2012-06-12 2015-03-05 제넨테크, 인크. 조건적 녹아웃 대립유전자의 생성 방법 및 이를 위한 조성물
ES2757623T3 (es) 2012-07-25 2020-04-29 Broad Inst Inc Proteínas de unión a ADN inducibles y herramientas de perturbación genómica y aplicaciones de las mismas
JP5952141B2 (ja) * 2012-08-31 2016-07-13 京セラメディカル株式会社 人工心肺ポンプ用駆動装置
ES2926021T3 (es) 2012-10-23 2022-10-21 Toolgen Inc Composición para escindir un ADN objetivo que comprende un ARN guía específico para el ADN objetivo y ácido nucleico codificador de proteína Cas o proteína Cas, y uso de la misma
PL2928496T3 (pl) 2012-12-06 2020-04-30 Sigma-Aldrich Co. Llc Modyfikacja i regulacja genomu w oparciu o CRISPR
WO2014093694A1 (en) 2012-12-12 2014-06-19 The Broad Institute, Inc. Crispr-cas nickase systems, methods and compositions for sequence manipulation in eukaryotes
US8697359B1 (en) 2012-12-12 2014-04-15 The Broad Institute, Inc. CRISPR-Cas systems and methods for altering expression of gene products
BR112015013784A2 (pt) 2012-12-12 2017-07-11 Massachusetts Inst Technology aplicação, manipulação e otimização de sistemas, métodos e composições para manipulação de sequência e aplicações terapêuticas
PL2898075T3 (pl) 2012-12-12 2016-09-30 PROJEKTOWANIE i OPTYMALIZACJA ULEPSZONYCH SYSTEMÓW, SPOSOBY I KOMPOZYCJE ENZYMÓW DO MANIPULACJI SEKWENCJĄ
EP2825654B1 (en) 2012-12-12 2017-04-26 The Broad Institute, Inc. Crispr-cas component systems, methods and compositions for sequence manipulation
US8993233B2 (en) 2012-12-12 2015-03-31 The Broad Institute Inc. Engineering and optimization of systems, methods and compositions for sequence manipulation with functional domains
RU2699523C2 (ru) 2012-12-17 2019-09-05 Президент Энд Фэллоуз Оф Харвард Коллидж Рнк-направляемая инженерия генома человека
JP6583918B2 (ja) * 2012-12-27 2019-10-02 キージーン ナムローゼ フェンノートシャップ 植物における遺伝連鎖を解消するための方法
WO2014127287A1 (en) 2013-02-14 2014-08-21 Massachusetts Institute Of Technology Method for in vivo tergated mutagenesis
CA2900992C (en) 2013-02-20 2023-02-28 Regeneron Pharmaceuticals, Inc. Genetic modification of rats
US10227610B2 (en) 2013-02-25 2019-03-12 Sangamo Therapeutics, Inc. Methods and compositions for enhancing nuclease-mediated gene disruption
WO2014131833A1 (en) 2013-02-27 2014-09-04 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
NZ712727A (en) 2013-03-14 2017-05-26 Caribou Biosciences Inc Compositions and methods of nucleic acid-targeting nucleic acids
US20140273230A1 (en) 2013-03-15 2014-09-18 Sigma-Aldrich Co., Llc Crispr-based genome modification and regulation
US9234213B2 (en) 2013-03-15 2016-01-12 System Biosciences, Llc Compositions and methods directed to CRISPR/Cas genomic engineering systems
WO2014153470A2 (en) 2013-03-21 2014-09-25 Sangamo Biosciences, Inc. Targeted disruption of t cell receptor genes using engineered zinc finger protein nucleases
CN105518146B (zh) 2013-04-04 2022-07-15 哈佛学院校长同事会 利用CRISPR/Cas系统的基因组编辑的治疗性用途
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
AU2014253942B9 (en) * 2013-04-16 2020-08-13 Regeneron Pharmaceuticals, Inc. Targeted modification of rat genome
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
WO2014182700A1 (en) 2013-05-10 2014-11-13 Sangamo Biosciences, Inc. Delivery methods and compositions for nuclease-mediated genome engineering
WO2014191518A1 (en) 2013-05-29 2014-12-04 Cellectis 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
WO2014201015A2 (en) 2013-06-11 2014-12-18 The Regents Of The University Of California Methods and compositions for target dna modification
CN105793425B (zh) 2013-06-17 2021-10-26 布罗德研究所有限公司 使用病毒组分靶向障碍和疾病的crispr-cas系统和组合物的递送、用途和治疗应用
EP3011029B1 (en) 2013-06-17 2019-12-11 The Broad Institute, Inc. Delivery, engineering and optimization of tandem guide systems, methods and compositions for sequence manipulation
WO2014204723A1 (en) 2013-06-17 2014-12-24 The Broad Institute Inc. Oncogenic models based on delivery and use of the crispr-cas systems, vectors and compositions
KR20160034901A (ko) 2013-06-17 2016-03-30 더 브로드 인스티튜트, 인코퍼레이티드 서열 조작에 최적화된 ｃｒｉｓｐｒ-ｃａｓ 이중 닉카아제 시스템, 방법 및 조성물
ES2767318T3 (es) 2013-06-17 2020-06-17 Broad Inst Inc Suministro, modificación y optimización de sistemas, métodos y composiciones para generar modelos y actuar sobre enfermedades y trastornos de células posmitóticas
CN107995927B (zh) 2013-06-17 2021-07-30 布罗德研究所有限公司 用于肝靶向和治疗的crispr-cas系统、载体和组合物的递送与用途
MX2015017110A (es) 2013-06-19 2016-08-03 Sigma Aldrich Co Llc Integracion dirigida.
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
JP2016528890A (ja) 2013-07-09 2016-09-23 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 ＣＲＩＳＰＲ／Ｃａｓ系を用いるゲノム編集の治療用の使用
US11060083B2 (en) 2013-07-19 2021-07-13 Larix Bioscience Llc Methods and compositions for producing double allele knock outs
JP6482546B2 (ja) 2013-07-19 2019-03-13 ラリクス・バイオサイエンス・リミテッド・ライアビリティ・カンパニーＬａｒｉｘ Ｂｉｏｓｃｉｅｎｃｅ， Ｌｌｃ 二重対立遺伝子ノックアウトを生成するための方法および組成物
CN105705188A (zh) 2013-07-24 2016-06-22 梅迪克艾克提乌销售有限公司 可更换盒
US10563225B2 (en) 2013-07-26 2020-02-18 President And Fellows Of Harvard College Genome engineering
EP3036334A1 (en) * 2013-08-22 2016-06-29 E. I. du Pont de Nemours and Company A soybean u6 polymerase iii promoter and methods of use
SG11201601313TA (en) 2013-08-29 2016-03-30 Univ Temple Methods and compositions for rna-guided treatment of hiv infection
DE202014010413U1 (de) 2013-09-18 2015-12-08 Kymab Limited Zellen und Organismen
WO2015048690A1 (en) 2013-09-27 2015-04-02 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
CN116836957A (zh) 2013-10-17 2023-10-03 桑格摩生物科学股份有限公司 用于核酸酶介导的基因组工程改造的递送方法和组合物
JP5900942B2 (ja) 2013-11-06 2016-04-06 国立大学法人広島大学 核酸挿入用ベクター
JP2016536021A (ja) 2013-11-07 2016-11-24 エディタス・メディシン，インコーポレイテッド ＣＲＩＳＰＲ関連方法および支配ｇＲＮＡのある組成物
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
RU2725520C2 (ru) 2013-12-11 2020-07-02 Регенерон Фармасьютикалс, Инк. Способы и композиции для направленной модификации генома
CA2932472A1 (en) 2013-12-12 2015-06-18 Massachusetts Institute Of Technology Compositions and methods of use of crispr-cas systems in nucleotide repeat disorders
AU2014361784A1 (en) 2013-12-12 2016-06-23 Massachusetts Institute Of Technology Delivery, use and therapeutic applications of the CRISPR-Cas systems and compositions for HBV and viral diseases and disorders
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
EP3080259B1 (en) 2013-12-12 2023-02-01 The Broad Institute, Inc. Engineering of systems, methods and optimized guide compositions with new architectures for sequence manipulation
JP2017501149A (ja) 2013-12-12 2017-01-12 ザ・ブロード・インスティテュート・インコーポレイテッド 粒子送達構成成分を用いた障害及び疾患の標的化のためのｃｒｉｓｐｒ−ｃａｓ系及び組成物の送達、使用及び治療適用
KR20160089527A (ko) 2013-12-12 2016-07-27 더 브로드 인스티튜트, 인코퍼레이티드 게놈 편집을 위한 ｃｒｉｓｐｒ-ｃａｓ 시스템 및 조성물의 전달, 용도 및 치료적 응용
CN106029886B (zh) 2013-12-19 2021-02-05 阿迈瑞斯公司 基因组整合的方法
AU2015204784B2 (en) 2014-01-08 2021-01-28 President And Fellows Of Harvard College RNA-guided gene drives
CA2936976A1 (en) 2014-01-24 2015-07-30 Children's Medical Center Corporation High-throughput mouse model for optimizing antibody affinities
WO2015116969A2 (en) 2014-01-30 2015-08-06 The Board Of Trustees Of The University Of Arkansas Method, vectors, cells, seeds and kits for stacking genes into a single genomic site
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
US11028388B2 (en) 2014-03-05 2021-06-08 Editas Medicine, Inc. CRISPR/Cas-related methods and compositions for treating Usher syndrome and retinitis pigmentosa
ES2745769T3 (es) 2014-03-10 2020-03-03 Editas Medicine Inc Procedimientos y composiciones relacionados con CRISPR/CAS para tratar la amaurosis congénita de Leber 10 (LCA10)
CA2942268A1 (en) 2014-03-12 2015-09-17 Precision Biosciences, Inc. Dystrophin gene exon deletion using engineered nucleases
KR102569558B1 (ko) 2014-03-14 2023-08-22 시버스 유에스 엘엘씨 올리고뉴클레오타이드 매개 유전자 보수를 사용한 표적화된 유전자 변형의 효율을 증가시키기 위한 방법 및 조성물
JP6815986B2 (ja) 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 大型家畜の接合体における標的化ゲノム編集
GB201406968D0 (en) 2014-04-17 2014-06-04 Green Biologics Ltd Deletion mutants
WO2015163733A1 (en) 2014-04-24 2015-10-29 Institute For Basic Science 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
WO2015173436A1 (en) 2014-05-16 2015-11-19 Vrije Universiteit Brussel Genetic correction of myotonic dystrophy type 1
BR112016028023A2 (pt) 2014-05-30 2017-08-22 Univ Leland Stanford Junior Composições e métodos de administração de tratamentos para infecções virais latentes
KR102374379B1 (ko) 2014-06-06 2022-03-17 리제너론 파마슈티칼스 인코포레이티드 표적화된 좌를 변형시키는 방법 및 조성물
EA039693B1 (ru) 2014-06-16 2022-02-28 Дзе Джонс Хопкинс Юниверсити Композиции и способы для экспрессии рнк-проводников crispr с использованием промотора h1
SG11201610633QA (en) 2014-06-26 2017-01-27 Regeneron Pharma Methods and compositions for targeted genetic modifications and methods of use
EP3169773B1 (en) 2014-07-15 2023-07-12 Juno Therapeutics, Inc. Engineered cells for adoptive cell therapy
US9944933B2 (en) 2014-07-17 2018-04-17 Georgia Tech Research Corporation Aptamer-guided gene targeting
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
CA2959070C (en) 2014-08-27 2020-11-10 Caribou Biosciences, Inc. Methods for increasing cas9-mediated engineering efficiency
US10570418B2 (en) 2014-09-02 2020-02-25 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
AU2015323973A1 (en) 2014-09-29 2017-04-20 The Jackson Laboratory High efficiency, high throughput generation of genetically modified mammals by electroporation
CA2963080A1 (en) 2014-10-01 2016-04-07 The General Hospital Corporation Methods for increasing efficiency of nuclease-induced homology-directed repair
AU2015330699B2 (en) 2014-10-10 2021-12-02 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
EP3561052A1 (en) 2014-10-15 2019-10-30 Regeneron Pharmaceuticals, Inc. Methods and compositions for generating or maintaining pluripotent cells
BR112017007923B1 (pt) 2014-10-17 2023-12-12 The Penn State Research Foundation Método para produzir manipulação genética mediada por reações multiplex com rna em uma célula receptora, construção de ácido nucleico,cassete de expressão, vetor, célula receptora e célula geneticamente modificada
US20170306306A1 (en) 2014-10-24 2017-10-26 Life Technologies Corporation Compositions and Methods for Enhancing Homologous Recombination
EP3215623A4 (en) 2014-11-06 2018-09-26 President and Fellows of Harvard College Cells lacking b2m surface expression and methods for allogeneic administration of such cells
AU2015342749B2 (en) 2014-11-07 2022-01-27 Editas Medicine, Inc. Methods for improving CRISPR/Cas-mediated genome-editing
KR102531016B1 (ko) 2014-11-21 2023-05-10 리제너론 파마슈티칼스 인코포레이티드 쌍 형성된 가이드 rna를 사용하는 표적화된 유전자 변형을 위한 방법 및 조성물
US10883111B2 (en) 2014-11-27 2021-01-05 Danziger Innovations Ltd. Nucleic acid constructs for genome editing
US20170266320A1 (en) 2014-12-01 2017-09-21 President And Fellows Of Harvard College RNA-Guided Systems for In Vivo Gene Editing
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)
WO2016094872A1 (en) 2014-12-12 2016-06-16 The Broad Institute Inc. Dead guides for crispr transcription factors
WO2016094874A1 (en) 2014-12-12 2016-06-16 The Broad Institute Inc. Escorted and functionalized guides for crispr-cas systems
WO2016097751A1 (en) 2014-12-18 2016-06-23 The University Of Bath Method of cas9 mediated genome engineering
CA2971213C (en) 2014-12-19 2023-09-26 Regeneron Pharmaceuticals, Inc. Methods and compositions for targeted genetic modification through single-step multiple targeting
WO2016104716A1 (ja) 2014-12-26 2016-06-30 国立研究開発法人理化学研究所 遺伝子のノックアウト方法
US20180155708A1 (en) 2015-01-08 2018-06-07 President And Fellows Of Harvard College Split Cas9 Proteins
US10280451B2 (en) 2015-01-09 2019-05-07 Bio-Rad Laboratories, Inc. Detection of genome editing
CN107429263A (zh) 2015-01-15 2017-12-01 斯坦福大学托管董事会 调控基因组编辑的方法
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
WO2016135559A2 (en) 2015-02-23 2016-09-01 Crispr Therapeutics Ag Materials and methods for treatment of human genetic diseases including hemoglobinopathies
BR112017017810A2 (pt) 2015-02-23 2018-04-10 Crispr Therapeutics Ag materiais e métodos para tratamento de hemoglobinopatias
GB2535532B (en) 2015-02-23 2021-05-12 Knorr Bremse Systeme Fuer Nutzfahrzeuge Gmbh Brake valve arrangement
EP3265560B1 (en) 2015-03-02 2021-12-08 Sinai Health System Homologous recombination factors
GB201504223D0 (en) 2015-03-12 2015-04-29 Genome Res Ltd Biallelic genetic modification
US20160281111A1 (en) 2015-03-26 2016-09-29 Editas Medicine, Inc. Crispr/cas-mediated gene conversion
CN115537396A (zh) 2015-03-27 2022-12-30 哈佛学院校长同事会 经过修饰的t细胞及其制备和使用方法
EP3748004A1 (en) 2015-04-01 2020-12-09 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
PT3289080T (pt) 2015-04-30 2021-11-19 Univ Columbia Terapia genética para doenças autossómicas dominantes
CA2986021A1 (en) 2015-05-16 2016-11-24 Genzyme Corporation Gene editing of deep intronic mutations
US9790490B2 (en) 2015-06-18 2017-10-17 The Broad Institute Inc. CRISPR enzymes and systems
KR20180054871A (ko) 2015-10-08 2018-05-24 프레지던트 앤드 펠로우즈 오브 하바드 칼리지 다중화 게놈 편집
CA2996329A1 (en) 2015-10-20 2017-04-27 Pioneer Hi-Bred International, Inc. Restoring function to a non-functional gene product via guided cas systems and methods of use
CN108471731A (zh) 2015-11-06 2018-08-31 杰克逊实验室 大型基因组dna敲入及其用途
EP3433363A1 (en) 2016-03-25 2019-01-30 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
RU2745563C2 (ru) 2016-05-20 2021-03-29 Регенерон Фармасьютикалс, Инк. Способы преодоления иммунологической толерантности с использованием множества направляющих рнк
US11643670B2 (en) 2018-01-29 2023-05-09 Massachusetts Institute Of Technology Methods of enhancing chromosomal homologous recombination

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