AU2015349692B2 - Methods and compositions for targeted genetic modification using paired guide RNAs - Google Patents

Methods and compositions for targeted genetic modification using paired guide RNAs Download PDF

Info

Publication number
AU2015349692B2
AU2015349692B2 AU2015349692A AU2015349692A AU2015349692B2 AU 2015349692 B2 AU2015349692 B2 AU 2015349692B2 AU 2015349692 A AU2015349692 A AU 2015349692A AU 2015349692 A AU2015349692 A AU 2015349692A AU 2015349692 B2 AU2015349692 B2 AU 2015349692B2
Authority
AU
Australia
Prior art keywords
dna
gene
targeting
targeted
deletion
Prior art date
Legal status (The legal status 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 status listed.)
Active
Application number
AU2015349692A
Other languages
English (en)
Other versions
AU2015349692A1 (en
Inventor
Wojtek Auerbach
Gustavo Droguett
David Frendewey
Anthony Gagliardi
Ka-Man Venus Lai
Lynn Macdonald
Andrew J. Murphy
David M. Valenzuela
Vera VORONINA
George D. Yancopoulos
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Regeneron Pharmaceuticals Inc
Original Assignee
Regeneron Pharmaceuticals Inc
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 Pharmaceuticals Inc filed Critical Regeneron Pharmaceuticals Inc
Publication of AU2015349692A1 publication Critical patent/AU2015349692A1/en
Application granted granted Critical
Publication of AU2015349692B2 publication Critical patent/AU2015349692B2/en
Priority to AU2021290301A priority Critical patent/AU2021290301B2/en
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • 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
    • A01K67/0275—Genetically modified vertebrates, e.g. transgenic
    • C—CHEMISTRY; METALLURGY
    • 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
    • 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
    • C12N15/10—Processes for the isolation, preparation or purification of DNA or RNA
    • C12N15/102—Mutagenizing nucleic acids
    • C—CHEMISTRY; METALLURGY
    • 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
    • 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
    • C—CHEMISTRY; METALLURGY
    • 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
    • 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
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • 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
    • C—CHEMISTRY; METALLURGY
    • 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
    • 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 [RNase]; Deoxyribonucleases [DNase]
    • 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
    • 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
    • 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
    • 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
    • C—CHEMISTRY; METALLURGY
    • 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 [CRISPR]
    • 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

Landscapes

  • Life Sciences & Earth Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Engineering & Computer Science (AREA)
  • Zoology (AREA)
  • Organic Chemistry (AREA)
  • Wood Science & Technology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Biotechnology (AREA)
  • General Engineering & Computer Science (AREA)
  • Molecular Biology (AREA)
  • Biomedical Technology (AREA)
  • General Health & Medical Sciences (AREA)
  • Biochemistry (AREA)
  • Microbiology (AREA)
  • Biophysics (AREA)
  • Physics & Mathematics (AREA)
  • Plant Pathology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Analytical Chemistry (AREA)
  • Environmental Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Animal Husbandry (AREA)
  • Biodiversity & Conservation Biology (AREA)
  • Mycology (AREA)
  • Immunology (AREA)
  • Cell Biology (AREA)
  • Crystallography & Structural Chemistry (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
  • Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Medicinal Preparation (AREA)
AU2015349692A 2014-11-21 2015-11-20 Methods and compositions for targeted genetic modification using paired guide RNAs Active AU2015349692B2 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU2021290301A AU2021290301B2 (en) 2014-11-21 2021-12-22 METHODS AND COMPOSITIONS FOR TARGETED GENETIC MODIFICATION USING PAIRED GUIDE RNAs

Applications Claiming Priority (7)

Application Number Priority Date Filing Date Title
US201462083005P 2014-11-21 2014-11-21
US62/083,005 2014-11-21
US201562182314P 2015-06-19 2015-06-19
US62/182,314 2015-06-19
US201562211421P 2015-08-28 2015-08-28
US62/211,421 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

Related Child Applications (1)

Application Number Title Priority Date Filing Date
AU2021290301A Division AU2021290301B2 (en) 2014-11-21 2021-12-22 METHODS AND COMPOSITIONS FOR TARGETED GENETIC MODIFICATION USING PAIRED GUIDE RNAs

Publications (2)

Publication Number Publication Date
AU2015349692A1 AU2015349692A1 (en) 2017-06-08
AU2015349692B2 true AU2015349692B2 (en) 2021-10-28

Family

ID=54771219

Family Applications (2)

Application Number Title Priority Date Filing Date
AU2015349692A Active AU2015349692B2 (en) 2014-11-21 2015-11-20 Methods and compositions for targeted genetic modification using paired guide RNAs
AU2021290301A Active AU2021290301B2 (en) 2014-11-21 2021-12-22 METHODS AND COMPOSITIONS FOR TARGETED GENETIC MODIFICATION USING PAIRED GUIDE RNAs

Family Applications After (1)

Application Number Title Priority Date Filing Date
AU2021290301A Active AU2021290301B2 (en) 2014-11-21 2021-12-22 METHODS AND COMPOSITIONS FOR TARGETED GENETIC MODIFICATION USING PAIRED GUIDE RNAs

Country Status (25)

Country Link
US (4) US10457960B2 (cg-RX-API-DMAC7.html)
EP (2) EP3221457B1 (cg-RX-API-DMAC7.html)
JP (2) JP6727199B2 (cg-RX-API-DMAC7.html)
KR (3) KR102683423B1 (cg-RX-API-DMAC7.html)
CN (2) CN107208078B (cg-RX-API-DMAC7.html)
AU (2) AU2015349692B2 (cg-RX-API-DMAC7.html)
BR (1) BR112017010547A2 (cg-RX-API-DMAC7.html)
CA (2) CA3176380A1 (cg-RX-API-DMAC7.html)
CY (1) CY1121738T1 (cg-RX-API-DMAC7.html)
DK (1) DK3221457T3 (cg-RX-API-DMAC7.html)
ES (2) ES2731437T3 (cg-RX-API-DMAC7.html)
HR (1) HRP20190949T1 (cg-RX-API-DMAC7.html)
HU (1) HUE044907T2 (cg-RX-API-DMAC7.html)
IL (3) IL301900A (cg-RX-API-DMAC7.html)
LT (1) LT3221457T (cg-RX-API-DMAC7.html)
MX (2) MX389266B (cg-RX-API-DMAC7.html)
NZ (1) NZ731962A (cg-RX-API-DMAC7.html)
PL (1) PL3221457T3 (cg-RX-API-DMAC7.html)
PT (1) PT3221457T (cg-RX-API-DMAC7.html)
RS (1) RS58893B1 (cg-RX-API-DMAC7.html)
RU (2) RU2734770C2 (cg-RX-API-DMAC7.html)
SG (2) SG11201703747RA (cg-RX-API-DMAC7.html)
SI (1) SI3221457T1 (cg-RX-API-DMAC7.html)
SM (1) SMT201900354T1 (cg-RX-API-DMAC7.html)
WO (1) WO2016081923A2 (cg-RX-API-DMAC7.html)

Families Citing this family (135)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6596541B2 (en) 2000-10-31 2003-07-22 Regeneron Pharmaceuticals, Inc. Methods of modifying eukaryotic cells
US20050144655A1 (en) 2000-10-31 2005-06-30 Economides Aris N. Methods of modifying eukaryotic cells
EP2395017A3 (en) 2003-05-30 2012-12-19 Merus B.V. Design and use of paired variable regions of specific binding molecules
US20100069614A1 (en) 2008-06-27 2010-03-18 Merus B.V. Antibody producing non-human mammals
EP2734621B1 (en) 2011-07-22 2019-09-04 President and Fellows of Harvard College Evaluation and improvement of nuclease cleavage specificity
EP2841572B1 (en) 2012-04-27 2019-06-19 Duke University Genetic correction of mutated genes
EP3561050B1 (en) 2013-02-20 2021-12-08 Regeneron Pharmaceuticals, Inc. Genetic modification of rats
US9828582B2 (en) 2013-03-19 2017-11-28 Duke University Compositions and methods for the induction and tuning of gene expression
HUE040575T2 (hu) 2013-04-16 2019-03-28 Regeneron Pharma A patkány genom célzott módosítása
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
US9322037B2 (en) 2013-09-06 2016-04-26 President And Fellows Of Harvard College Cas9-FokI fusion proteins and uses thereof
US9228207B2 (en) 2013-09-06 2016-01-05 President And Fellows Of Harvard College Switchable gRNAs comprising aptamers
US9526784B2 (en) 2013-09-06 2016-12-27 President And Fellows Of Harvard College Delivery system for functional nucleases
CN106459995B (zh) 2013-11-07 2020-02-21 爱迪塔斯医药有限公司 使用统治型gRNA的CRISPR相关方法和组合物
US9546384B2 (en) 2013-12-11 2017-01-17 Regeneron Pharmaceuticals, Inc. Methods and compositions for the targeted modification of a mouse genome
US9840699B2 (en) 2013-12-12 2017-12-12 President And Fellows Of Harvard College Methods for nucleic acid editing
LT3152312T (lt) 2014-06-06 2020-04-27 Regeneron Pharmaceuticals, Inc. Tikslinio lokuso modifikavimo būdai ir kompozicijos
EP3461885B1 (en) 2014-06-26 2021-10-20 Regeneron Pharmaceuticals, Inc. Methods and compositions for targeted genetic modifications and methods of use
US10077453B2 (en) 2014-07-30 2018-09-18 President And Fellows Of Harvard College CAS9 proteins including ligand-dependent inteins
EP3204496A1 (en) 2014-10-10 2017-08-16 Editas Medicine, Inc. Compositions and methods for promoting homology directed repair
JP2017536811A (ja) 2014-10-15 2017-12-14 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Ｒｅｇｅｎｅｒｏｎ Ｐｈａｒｍａｃｅｕｔｉｃａｌｓ， Ｉｎｃ． 多能性細胞の樹立又は維持のための方法及び組成物
WO2016073990A2 (en) 2014-11-07 2016-05-12 Editas Medicine, Inc. Methods for improving crispr/cas-mediated genome-editing
HUE044907T2 (hu) 2014-11-21 2019-11-28 Regeneron Pharma Módszerek és készítmények célzott genetikai módosításhoz, párosított mutató RNS-ek használatával
NZ732895A (en) 2014-12-19 2022-05-27 Regeneron Pharma Methods and compositions for targeted genetic modification through single-step multiple targeting
US10676726B2 (en) 2015-02-09 2020-06-09 Duke University Compositions and methods for epigenome editing
JP7030522B2 (ja) 2015-05-11 2022-03-07 エディタス・メディシン、インコーポレイテッド 幹細胞における遺伝子編集のための最適化ｃｒｉｓｐｒ／ｃａｓ９システムおよび方法
ES3009538T3 (en) 2015-05-29 2025-03-27 Regeneron Pharma Rodent cells having a disruption in a c9orf72 locus
US11911415B2 (en) 2015-06-09 2024-02-27 Editas Medicine, Inc. CRISPR/Cas-related methods and compositions for improving transplantation
WO2017011721A1 (en) 2015-07-15 2017-01-19 Rutgers, The State University Of New Jersey Nuclease-independent targeted gene editing platform and uses thereof
CA2999500A1 (en) 2015-09-24 2017-03-30 Editas Medicine, Inc. Use of exonucleases to improve crispr/cas-mediated genome editing
US11970710B2 (en) 2015-10-13 2024-04-30 Duke University Genome engineering with Type I CRISPR systems in eukaryotic cells
SG10202104041PA (en) 2015-10-23 2021-06-29 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
EP3384055B1 (en) 2015-11-30 2025-07-16 Duke University Therapeutic targets for the correction of the human dystrophin gene by gene editing and methods of use
KR102482103B1 (ko) 2016-01-13 2022-12-28 리제너론 파마슈티칼스 인코포레이티드 조작된 중쇄 다양성 영역을 갖는 설치류
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
US20190127713A1 (en) 2016-04-13 2019-05-02 Duke University Crispr/cas9-based repressors for silencing gene targets in vivo and methods of use
WO2017180694A1 (en) 2016-04-13 2017-10-19 Editas Medicine, Inc. Cas9 fusion molecules gene editing systems, and methods of use thereof
AU2017268458B2 (en) 2016-05-20 2022-07-21 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
WO2017219033A1 (en) * 2016-06-17 2017-12-21 Montana State University Bidirectional targeting for genome editing
WO2017220527A1 (en) * 2016-06-20 2017-12-28 Glycotope Gmbh Means and methods for modifying multiple alleles
WO2018001241A1 (zh) * 2016-06-28 2018-01-04 北京百奥赛图基因生物技术有限公司 一种pd-1基因修饰人源化动物模型的构建方法及其应用
CN109863143B (zh) 2016-07-13 2021-10-15 威泰克斯制药公司 提高基因组编辑效率的方法、组合物和试剂盒
US12214056B2 (en) 2016-07-19 2025-02-04 Duke University Therapeutic applications of CPF1-based genome editing
EP3491130B1 (en) 2016-07-28 2022-07-27 DSM IP Assets B.V. An assembly system for a eukaryotic cell
CN109803530A (zh) 2016-07-29 2019-05-24 瑞泽恩制药公司 包含引起c-截短的原纤维蛋白-1表达的突变的小鼠
KR102827276B1 (ko) 2016-08-03 2025-07-01 프레지던트 앤드 펠로우즈 오브 하바드 칼리지 아데노신 핵염기 편집제 및 그의 용도
WO2018031683A1 (en) 2016-08-09 2018-02-15 President And Fellows Of Harvard College Programmable cas9-recombinase fusion proteins and uses thereof
WO2018039438A1 (en) 2016-08-24 2018-03-01 President And Fellows Of Harvard College Incorporation of unnatural amino acids into proteins using base editing
KR102294755B1 (ko) 2016-09-30 2021-08-31 리제너론 파마슈티칼스 인코포레이티드 C9orf72 유전자좌에서 헥사뉴클레오티드 반복 확장을 갖는 비인간 동물
CN110214180A (zh) 2016-10-14 2019-09-06 哈佛大学的校长及成员们 核碱基编辑器的aav递送
PL3766343T3 (pl) 2016-11-04 2022-09-26 Regeneron Pharmaceuticals, Inc. Zwierzęta inne niż człowiek posiadające zmodyfikowany sposobami inżynierii locus łańcucha lekkiego lambda immunoglobuliny
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
US12286727B2 (en) 2016-12-19 2025-04-29 Editas Medicine, Inc. Assessing nuclease cleavage
US10745677B2 (en) 2016-12-23 2020-08-18 President And Fellows Of Harvard College Editing of CCR5 receptor gene to protect against HIV infection
US12065666B2 (en) 2017-01-05 2024-08-20 Rutgers, The State University Of New Jersey Targeted gene editing platform independent of DNA double strand break and uses thereof
JP7229923B2 (ja) 2017-01-06 2023-02-28 エディタス・メディシン、インコーポレイテッド ヌクレアーゼ切断を評価する方法
CA3053499A1 (en) 2017-02-15 2018-08-23 Bluebird Bio, Inc. Donor repair templates multiplex genome editing
JP2020510038A (ja) 2017-03-09 2020-04-02 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 がんワクチン
WO2018165504A1 (en) 2017-03-09 2018-09-13 President And Fellows Of Harvard College Suppression of pain by gene editing
KR20190127797A (ko) 2017-03-10 2019-11-13 프레지던트 앤드 펠로우즈 오브 하바드 칼리지 시토신에서 구아닌으로의 염기 편집제
GB2575930A (en) 2017-03-23 2020-01-29 Harvard College Nucleobase editors comprising 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
CN111132694B (zh) * 2017-05-16 2024-12-03 健艾仕生物医药有限公司 治疗阿尔茨海默病的组合物和方法
EP3635104A1 (en) 2017-06-09 2020-04-15 Editas Medicine, Inc. Engineered cas9 nucleases
SG11201911886PA (en) 2017-06-27 2020-01-30 Regeneron Pharma 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
US11732274B2 (en) 2017-07-28 2023-08-22 President And Fellows Of Harvard College Methods and compositions for evolving base editors using phage-assisted continuous evolution (PACE)
ES3033963T3 (en) 2017-07-31 2025-08-11 Regeneron Pharma Method of testing the ability of a crispr/cas9 nuclease to modify a target genomic locus in vivo, by making use of a cas-transgenic mouse or rat which comprises a cas9 expression cassette in its genome
US11021719B2 (en) 2017-07-31 2021-06-01 Regeneron Pharmaceuticals, Inc. Methods and compositions for assessing CRISPER/Cas-mediated disruption or excision and CRISPR/Cas-induced recombination with an exogenous donor nucleic acid in vivo
EP3676376B1 (en) 2017-08-30 2025-01-15 President and Fellows of Harvard College High efficiency base editors comprising gam
WO2019067875A1 (en) 2017-09-29 2019-04-04 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
CA3082251A1 (en) 2017-10-16 2019-04-25 The Broad Institute, Inc. Uses of adenosine base editors
US20190141966A1 (en) 2017-11-10 2019-05-16 Regeneron Pharmaceuticals, Inc. Non-Human Animals Comprising SLC30A8 Mutation And Methods Of Use
AU2018375796B2 (en) 2017-11-30 2024-11-21 Regeneron Pharmaceuticals, Inc. Non-human animals comprising a humanized TRKB locus
PT3720279T (pt) 2017-12-05 2022-10-06 Regeneron Pharma Ratinhos tendo uma cadeia leve lambda de imunoglobulina manipulada e seus usos
EP3724214A4 (en) 2017-12-15 2021-09-01 The Broad Institute Inc. SYSTEMS AND METHODS FOR PREDICTING REPAIR RESULTS IN GENETIC ENGINEERING
BR112020013626A2 (pt) 2018-01-17 2020-12-01 Vertex Pharmaceuticals Incorporated compostos de quinoxalinona, composições, métodos e kits para aumentar a eficiência de edição de genoma
EA202091709A1 (ru) * 2018-01-17 2020-11-10 Вертекс Фармасьютикалз Инкорпорейтед Ингибиторы днк-пк
AU2019209293B2 (en) 2018-01-17 2023-07-27 Vertex Pharmaceuticals Incorporated DNA-PK inhibitors
WO2019148166A1 (en) * 2018-01-29 2019-08-01 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
WO2019189573A1 (ja) 2018-03-29 2019-10-03 学校法人自治医科大学 ゲノム編集方法、組成物、細胞、細胞製剤、及び細胞製剤の製造方法
WO2019213183A1 (en) * 2018-04-30 2019-11-07 The Trustees Of The University Of Pennsylvania In utero crispr-mediated therapeutic editing of genes
CN112218945A (zh) * 2018-05-08 2021-01-12 国立大学法人大阪大学 纯合细胞的制作方法
WO2019222545A1 (en) 2018-05-16 2019-11-21 Synthego Corporation Methods and systems for guide rna design and use
WO2019226953A1 (en) 2018-05-23 2019-11-28 The Broad Institute, Inc. Base editors and uses thereof
IL318469A (en) 2018-06-14 2025-03-01 Regeneron Pharma Non-human animals capable of reorganizing transgenic DH-DH, and their uses
EP3823633A4 (en) 2018-06-29 2023-05-03 Editas Medicine, Inc. SYNTHETIC LEAD MOLECULES, COMPOSITIONS AND METHODS RELATED THERETO
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 (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
US20220053741A1 (en) 2018-09-13 2022-02-24 Regeneron Pharmaceuticals, Inc. Complement Factor H Gene Knockout Rat as a Model of C3 Glomerulopathy
WO2020067004A1 (ja) * 2018-09-25 2020-04-02 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
US12281338B2 (en) 2018-10-29 2025-04-22 The Broad Institute, Inc. Nucleobase editors comprising GeoCas9 and uses thereof
CN113423831B (zh) 2018-12-20 2023-03-10 瑞泽恩制药公司 核酸酶介导的重复扩增
US12351837B2 (en) 2019-01-23 2025-07-08 The Broad Institute, Inc. Supernegatively charged proteins and uses thereof
DE112020001306T5 (de) 2019-03-19 2022-01-27 Massachusetts Institute Of Technology Verfahren und zusammensetzungen zur editierung von nukleotidsequenzen
IL286905B2 (en) 2019-04-04 2024-06-01 Regeneron Pharma Non-human animals containing the human coagulation factor 12 locus
US12473543B2 (en) 2019-04-17 2025-11-18 The Broad Institute, Inc. Adenine base editors with reduced off-target effects
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
CA3136478A1 (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
US12435330B2 (en) 2019-10-10 2025-10-07 The Broad Institute, Inc. Methods and compositions for prime editing RNA
WO2021108363A1 (en) 2019-11-25 2021-06-03 Regeneron Pharmaceuticals, Inc. Crispr/cas-mediated upregulation of humanized ttr allele
US12250931B2 (en) 2020-01-28 2025-03-18 Regeneron Pharmaceuticals, Inc. Genetically modified mouse with a humanized PNPLA3 gene 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 (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
AU2021267940A1 (en) 2020-05-08 2022-12-08 President And Fellows Of Harvard College Methods and compositions for simultaneous editing of both strands of a target double-stranded nucleotide sequence
US20230232796A1 (en) 2020-06-26 2023-07-27 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
KR20220064170A (ko) 2020-11-11 2022-05-18 삼성전자주식회사 이미지 센서를 포함하는 전자 장치 및 그 동작 방법
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
EP4559939A3 (en) 2020-12-23 2025-09-24 Regeneron Pharmaceuticals, Inc. Nucleic acids encoding anchor modified antibodies and uses therof
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
US20250027116A1 (en) * 2021-09-24 2025-01-23 Immunocan Biotech Co. Ltd. Methods for large-size chromosomal transfer and modified chromosomes and organisims using same
JP7672012B2 (ja) * 2021-09-30 2025-05-07 国立大学法人大阪大学 相同染色体の一方に特異的なｄｎａ欠失を有する細胞を製造する方法
EP4423271A2 (en) 2021-10-28 2024-09-04 Regeneron Pharmaceuticals, Inc. Crispr/cas-related methods and compositions for knocking out c5
IL312971A (en) 2021-12-08 2024-07-01 Regeneron Pharma 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
EP4475671A1 (en) 2022-02-07 2024-12-18 Regeneron Pharmaceuticals, Inc. Compositions and methods for defining optimal treatment timeframes in lysosomal disease
KR20240144138A (ko) 2022-02-11 2024-10-02 리제너론 파마슈티칼스 인코포레이티드 4r 타우 표적화제를 스크리닝하기 위한 조성물 및 방법
CA3260237A1 (en) 2022-06-24 2023-12-28 Tune Therapeutics, Inc. Compositions, systems and methods for reducing low-density lipoprotein by 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
KR20250027489A (ko) * 2023-08-16 2025-02-26 기초과학연구원 단일가닥 절단 활성을 가지는 CRISPR/Cas 시스템과 PARP 억제제를 이용하는 세포 사멸 방법
WO2025250495A1 (en) 2024-05-28 2025-12-04 Regeneron Pharmaceuticals, Inc. Acceleration of human hepatocyte engraftment in humanized liver animals by supplementing paracrine ligands or agonists that activate human liver regeneration signals

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
AU8587598A (en) 1997-07-26 1999-02-16 Wisconsin Alumni Research Foundation Trans-species nuclear transfer
WO2000039316A1 (en) 1998-12-31 2000-07-06 The J. David Gladstone Institutes Transgenic rodents and rodent cell lines expressing hiv co-receptors
US6503717B2 (en) 1999-12-06 2003-01-07 Sangamo Biosciences, Inc. Methods of using randomized libraries of zinc finger proteins for the identification of gene function
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
ATE387909T1 (de) 2000-05-31 2008-03-15 Novartis Vaccines & Diagnostic Verfahren und zusammensetzungen zur behandlung von neoplastischen erkrankungen mittels chemotherapie und strahlungssensibilisatoren
US20050144655A1 (en) 2000-10-31 2005-06-30 Economides Aris N. Methods of modifying eukaryotic cells
US6586251B2 (en) 2000-10-31 2003-07-01 Regeneron Pharmaceuticals, Inc. Methods of modifying eukaryotic cells
US6596541B2 (en) 2000-10-31 2003-07-22 Regeneron Pharmaceuticals, Inc. 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 (zh) 2002-01-23 2009-12-30 犹他大学研究基金会 使用锌指核酸酶的定向染色体诱变
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
WO2004063356A2 (en) 2003-01-13 2004-07-29 Rao Mahendra S Persistent expression of candidate molecule in proliferating stem and progenitor cells for delivery of therapeutic products
ATE521341T1 (de) 2003-12-01 2011-09-15 Kudos Pharm Ltd Dna-schäden-reparatur-hemmer zur behandlung von krebs
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
EP2003960B1 (en) 2006-03-31 2015-06-10 E. R. Squibb & Sons, L.L.C. Transgenic animals expressing chimeric antibodies for use in preparing human antibodies
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
EP2137310B1 (en) 2007-04-26 2010-11-24 Sangamo BioSciences, Inc. Targeted integration into the ppp1r12c locus
SI2602323T1 (en) 2007-06-01 2018-05-31 Open Monoclonal Technology, Inc. Compositions and procedures for inhibiting endogenous immunoglobin gene and the formation of transgenic human idiopathic antibodies
KR20160015400A (ko) 2008-08-22 2016-02-12 상가모 바이오사이언스 인코포레이티드 표적화된 단일가닥 분할 및 표적화된 통합을 위한 방법 및 조성물
CA2745031C (en) 2008-12-04 2018-08-14 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
US20120276537A1 (en) 2009-10-28 2012-11-01 Kuehn Ralf Homologous recombination in the oocyte
JP5908405B2 (ja) 2009-10-29 2016-04-26 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Ｒｅｇｅｎｅｒｏｎ Ｐｈａｒｍａｃｅｕｔｉｃａｌｓ， Ｉｎｃ． 多機能性対立遺伝子
US20120315670A1 (en) 2009-11-02 2012-12-13 Gen9, Inc. Compositions and Methods for the Regulation of Multiple Genes of Interest in a Cell
EP2508595B1 (en) 2009-12-01 2016-11-23 National Cancer Center Method for constructing chimeric rat using rat embryonic stem cells
AU2010335107B2 (en) 2009-12-21 2014-07-03 Keygene N.V. Improved techniques for transfecting protoplasts
KR101951489B1 (ko) 2010-01-22 2019-04-22 다우 아그로사이언시즈 엘엘씨 유전적으로 변형된 유기체에서 도입유전자의 절제
JP2013518602A (ja) 2010-02-09 2013-05-23 サンガモ バイオサイエンシーズ， インコーポレイテッド 部分的に一本鎖のドナー分子による標的化ゲノム改変
WO2011146121A1 (en) 2010-05-17 2011-11-24 Sangamo Biosciences, Inc. Novel dna-binding proteins and uses thereof
GB201009732D0 (en) 2010-06-10 2010-07-21 Gene Bridges Gmbh Direct cloning
CN102933074B (zh) 2010-06-11 2015-04-08 瑞泽恩制药公司 由xy es细胞制备能育的xy雌性动物
CA2805442C (en) 2010-07-21 2020-05-12 Sangamo Biosciences, Inc. Methods and compositions for modification of an 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
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
IN2014CN03890A (cg-RX-API-DMAC7.html) 2011-10-28 2015-10-16 Regeneron Pharma
WO2013141680A1 (en) 2012-03-20 2013-09-26 Vilnius University RNA-DIRECTED DNA CLEAVAGE BY THE Cas9-crRNA COMPLEX
US9637739B2 (en) 2012-03-20 2017-05-02 Vilnius University RNA-directed DNA cleavage by the Cas9-crRNA complex
PT2847335T (pt) 2012-04-25 2018-09-28 Regeneron Pharma Alvejamento mediado por nuclease com vetores de alvejamento grandes
AU2013259647B2 (en) 2012-05-07 2018-11-08 Corteva Agriscience Llc Methods and compositions for nuclease-mediated targeted integration of transgenes
WO2013176772A1 (en) 2012-05-25 2013-11-28 The Regents Of The University Of California Methods and compositions for rna-directed target dna modification and for rna-directed modulation of transcription
MX2014015204A (es) 2012-06-12 2015-08-07 Genentech Inc Metodos y composiciones para generar alelos con inactivacion condicional.
EP3808844A1 (en) 2012-07-25 2021-04-21 The Broad Institute, Inc. Inducible dna binding proteins and genome perturbation tools and applications thereof
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
CN110643600A (zh) 2012-10-23 2020-01-03 基因工具股份有限公司 用于切割靶dna的系统及其用途
LT3138910T (lt) 2012-12-06 2017-11-10 Sigma-Aldrich Co. Llc Crispr pagrįstas genomo modifikavimas ir reguliavimas
ES2786193T3 (es) 2012-12-12 2020-10-09 Broad Inst Inc Modificación por tecnología genética y optimización de sistemas, métodos y composiciones enzimáticas mejorados para la manipulación de secuencias
US8697359B1 (en) 2012-12-12 2014-04-15 The Broad Institute, Inc. CRISPR-Cas systems and methods for altering expression of gene products
SG10201707569YA (en) 2012-12-12 2017-10-30 Broad Inst Inc Delivery, Engineering and Optimization of Systems, Methods and Compositions for Sequence Manipulation and Therapeutic Applications
WO2014093655A2 (en) 2012-12-12 2014-06-19 The Broad Institute, Inc. Engineering and optimization of systems, methods and compositions for sequence manipulation with functional domains
EP2840140B2 (en) 2012-12-12 2023-02-22 The Broad Institute, Inc. Crispr-Cas based method for mutation of prokaryotic cells
US20140310830A1 (en) 2012-12-12 2014-10-16 Feng Zhang CRISPR-Cas Nickase Systems, Methods And Compositions For Sequence Manipulation in Eukaryotes
SG10201704932UA (en) 2012-12-17 2017-07-28 Harvard College Rna-guided human genome engineering
CN105025701B (zh) * 2012-12-27 2018-09-25 凯津公司 去除植物中遗传连锁的方法
WO2014127287A1 (en) 2013-02-14 2014-08-21 Massachusetts Institute Of Technology Method for in vivo tergated mutagenesis
EP3561050B1 (en) 2013-02-20 2021-12-08 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
WO2014143381A1 (en) * 2013-03-09 2014-09-18 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
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
EP2975942B1 (en) 2013-03-21 2018-08-08 Sangamo Therapeutics, Inc. Targeted disruption of t cell receptor genes using engineered zinc finger protein nucleases
CN115261411A (zh) 2013-04-04 2022-11-01 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
WO2014172458A1 (en) 2013-04-16 2014-10-23 University Of Washington Through Its Center For Commercialization Activating an alternative pathway for homology-directed repair to stimulate targeted gene correction and genome engineering
WO2014172470A2 (en) 2013-04-16 2014-10-23 Whitehead Institute For Biomedical Research Methods of mutating, modifying or modulating nucleic acid in a cell or nonhuman mammal
HUE040575T2 (hu) 2013-04-16 2019-03-28 Regeneron Pharma A patkány genom célzott módosítása
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
AU2014262867B2 (en) 2013-05-10 2019-12-05 Sangamo Therapeutics, Inc. Delivery methods and compositions for nuclease-mediated genome engineering
AU2014273082B2 (en) 2013-05-29 2018-11-08 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
EP3008181B1 (en) 2013-06-11 2019-11-06 The Regents of The University of California Methods and compositions for target dna modification
ES2777217T3 (es) 2013-06-17 2020-08-04 Broad Inst Inc Suministro, modificación y optimización de sistemas de guía en tándem, métodos y composiciones para la manipulación de secuencias
EP3825406A1 (en) 2013-06-17 2021-05-26 The Broad Institute Inc. Delivery and use of the crispr-cas systems, vectors and compositions for hepatic targeting and therapy
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
SG11201510327TA (en) 2013-06-17 2016-01-28 Broad Inst Inc Delivery, engineering and optimization of systems, methods and compositions for targeting and modeling diseases and disorders of post mitotic cells
WO2014204725A1 (en) 2013-06-17 2014-12-24 The Broad Institute Inc. Optimized crispr-cas double nickase systems, methods and compositions for sequence manipulation
CA2915795C (en) 2013-06-17 2021-07-13 The Broad Institute, Inc. Delivery, use and therapeutic applications of the crispr-cas systems and compositions for targeting disorders and diseases using viral components
JP2016523084A (ja) 2013-06-19 2016-08-08 シグマ−アルドリッチ・カンパニー・リミテッド・ライアビリティ・カンパニーＳｉｇｍａ−Ａｌｄｒｉｃｈ Ｃｏ．， ＬＬＣ 標的組込み
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
EP3019595A4 (en) 2013-07-09 2016-11-30 THERAPEUTIC USES OF A GENERIC CHANGE WITH CRISPR / CAS SYSTEMS
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
JP2016525004A (ja) 2013-07-24 2016-08-22 メディック アクティフ フェアトリープス ゲーエムベーハー 食材細断装置
US10563225B2 (en) 2013-07-26 2020-02-18 President And Fellows Of Harvard College Genome engineering
CA3221516A1 (en) * 2013-08-22 2015-02-26 E. I. Du Pont De Nemours And Company Plant genome modification using guide rna/cas endonuclease systems and methods of use
KR20160060659A (ko) 2013-08-29 2016-05-30 템플 유니버시티-오브 더 커먼웰쓰 시스템 오브 하이어 에듀케이션 Hiv 감염증의 rna-유도 치료를 위한 방법 및 조성물
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
US20160237455A1 (en) 2013-09-27 2016-08-18 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
US20160264995A1 (en) 2013-11-06 2016-09-15 Hiroshima University Vector for Nucleic Acid Insertion
CN106459995B (zh) 2013-11-07 2020-02-21 爱迪塔斯医药有限公司 使用统治型gRNA的CRISPR相关方法和组合物
US10787684B2 (en) 2013-11-19 2020-09-29 President And Fellows Of Harvard College Large gene excision and insertion
JP2016538001A (ja) 2013-11-28 2016-12-08 ホライズン・ジェノミクス・ゲーエムベーハー 体細胞半数体ヒト細胞株
US9546384B2 (en) 2013-12-11 2017-01-17 Regeneron Pharmaceuticals, Inc. Methods and compositions for the targeted modification of a mouse genome
AU2014362248A1 (en) 2013-12-12 2016-06-16 Massachusetts Institute Of Technology Compositions and methods of use of CRISPR-Cas systems in nucleotide repeat disorders
EP3080260B1 (en) 2013-12-12 2019-03-06 The Broad Institute, Inc. Crispr-cas systems and methods for altering expression of gene products, structural information and inducible modular cas enzymes
CN106536729A (zh) 2013-12-12 2017-03-22 布罗德研究所有限公司 使用粒子递送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
WO2015089465A1 (en) 2013-12-12 2015-06-18 The Broad Institute Inc. Delivery, use and therapeutic applications of the crispr-cas systems and compositions for hbv and viral diseases and disorders
AU2014361781B2 (en) 2013-12-12 2021-04-01 Massachusetts Institute Of Technology Delivery, use and therapeutic applications of the CRISPR -Cas systems and compositions for genome editing
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
MX2016007797A (es) 2013-12-19 2016-09-07 Amyris Inc Metodos para integracion genomica.
CN106133141B (zh) 2014-01-08 2021-08-20 哈佛学院董事及会员团体 Rna引导的基因驱动
EP3096609B1 (en) 2014-01-24 2021-09-22 Children's Medical Center Corporation High-throughput mouse model for optimizing antibody affinities
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
WO2015117041A1 (en) 2014-01-30 2015-08-06 Nair Ramesh B Gene modification-mediated methods and compositions for generating dominant traits in eukaryotic systems
EP3957735A1 (en) 2014-03-05 2022-02-23 Editas Medicine, Inc. Crispr/cas-related methods and compositions for treating usher syndrome and retinitis pigmentosa
EP3116997B1 (en) 2014-03-10 2019-05-15 Editas Medicine, Inc. Crispr/cas-related methods and compositions for treating leber's congenital amaurosis 10 (lca10)
ES2821149T3 (es) 2014-03-12 2021-04-23 Prec Biosciences Inc Eliminación del exón del gen de la distrofina mediante nucleasas modificadas genéticamente
UA124375C2 (uk) 2014-03-14 2021-09-08 Кібус Юс Ллс Спосіб здійснення спрямованої генетичної зміни днк в клітині рослини з використанням нуклеази crispr і модифікованого gron
AU2015236033B2 (en) 2014-03-26 2018-06-07 University Of Maryland, College Park Targeted genome editing in zygotes of domestic large animals
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
US20170088819A1 (en) 2014-05-16 2017-03-30 Vrije Universiteit Brussel Genetic correction of myotonic dystrophy type 1
US20160060655A1 (en) 2014-05-30 2016-03-03 The Board Of Trustees Of The Leland Stanford Junior University Compositions and methods to treat latent viral infections
LT3152312T (lt) 2014-06-06 2020-04-27 Regeneron Pharmaceuticals, Inc. Tikslinio lokuso modifikavimo būdai ir kompozicijos
EP3155101B1 (en) 2014-06-16 2020-01-29 The Johns Hopkins University Compositions and methods for the expression of crispr guide rnas using the h1 promoter
EP3461885B1 (en) 2014-06-26 2021-10-20 Regeneron Pharmaceuticals, Inc. Methods and compositions for targeted genetic modifications and methods of use
CA2954414A1 (en) 2014-07-15 2016-01-21 Juno Therapeutics, Inc. 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
WO2016033246A1 (en) 2014-08-27 2016-03-03 Caribou Biosciences, Inc. Methods for increasing cas9-mediated engineering efficiency
EP3188763B1 (en) 2014-09-02 2020-05-13 The Regents of The University of California Methods and compositions for rna-directed target dna modification
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
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
WO2016049258A2 (en) 2014-09-25 2016-03-31 The Broad Institute Inc. Functional screening with optimized functional crispr-cas systems
SG11201702074VA (en) 2014-09-29 2017-04-27 Jackson Lab High efficiency, high throughput generation of genetically modified mammals by electroporation
IL287561B2 (en) 2014-10-01 2024-03-01 Massachusetts Gen Hospital Methods for increasing efficiency of nuclease-induced homology-directed repair
EP3204496A1 (en) 2014-10-10 2017-08-16 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
JP2017536811A (ja) 2014-10-15 2017-12-14 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Ｒｅｇｅｎｅｒｏｎ Ｐｈａｒｍａｃｅｕｔｉｃａｌｓ， Ｉｎｃ． 多能性細胞の樹立又は維持のための方法及び組成物
US10308947B2 (en) 2014-10-17 2019-06-04 The Penn State Research Foundation Methods and compositions for multiplex RNA guided genome editing and other RNA technologies
WO2016065364A1 (en) 2014-10-24 2016-04-28 Life Technologies Corporation Compositions and methods for enhancing homologous recombination
US12180263B2 (en) 2014-11-06 2024-12-31 President And Fellows Of Harvard College Cells lacking B2M surface expression and methods for allogeneic administration of such cells
WO2016073990A2 (en) 2014-11-07 2016-05-12 Editas Medicine, Inc. Methods for improving crispr/cas-mediated genome-editing
HUE044907T2 (hu) 2014-11-21 2019-11-28 Regeneron Pharma Módszerek és készítmények célzott genetikai módosításhoz, párosított mutató RNS-ek használatával
KR20170081268A (ko) 2014-11-27 2017-07-11 단지거 이노베이션즈 엘티디. 게놈 편집용 핵산 구조체
WO2016089866A1 (en) 2014-12-01 2016-06-09 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)
WO2016094874A1 (en) 2014-12-12 2016-06-16 The Broad Institute Inc. Escorted and functionalized guides for crispr-cas systems
EP3230452B1 (en) 2014-12-12 2025-06-11 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
NZ732895A (en) 2014-12-19 2022-05-27 Regeneron Pharma Methods and compositions for targeted genetic modification through single-step multiple targeting
JPWO2016104716A1 (ja) 2014-12-26 2017-10-05 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
WO2016112242A1 (en) 2015-01-08 2016-07-14 President And Fellows Of Harvard College Split cas9 proteins
EP3242938B1 (en) 2015-01-09 2020-01-08 Bio-Rad Laboratories, Inc. Detection of genome editing
WO2016115326A1 (en) 2015-01-15 2016-07-21 The Board Of Trustees Of The Leland Stanford Junior University Methods for modulating genome editing
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
US12129471B2 (en) 2015-02-23 2024-10-29 Vertex Pharmaceuticals Incorporated Materials and methods for treatment of human genetic diseases including hemoglobinopathies
GB2535532B (en) 2015-02-23 2021-05-12 Knorr Bremse Systeme Fuer Nutzfahrzeuge Gmbh Brake valve arrangement
CN107532168A (zh) 2015-02-23 2018-01-02 克里斯珀医疗股份公司 治疗血红蛋白病的材料和方法
US11261466B2 (en) 2015-03-02 2022-03-01 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
EP4269601A3 (en) 2015-03-27 2024-01-10 President and Fellows of Harvard College Modified t cells and methods of making and using the same
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
WO2016168890A1 (en) 2015-04-22 2016-10-27 Genea Ip Holdings Pty Ltd Generation of muscle-lineage cells from stem cells
CA2983364A1 (en) 2015-04-27 2016-11-03 Genethon Compositions and methods for the treatment of nucleotide repeat expansion disorders
EP4008780A1 (en) 2015-04-30 2022-06-08 The Trustees of Columbia University in the City of New York Gene therapy for autosomal dominant diseases
AU2016265255B2 (en) 2015-05-16 2022-03-17 Genzyme Corporation Gene editing of deep intronic mutations
US9790490B2 (en) 2015-06-18 2017-10-17 The Broad Institute Inc. CRISPR enzymes and systems
KR102880582B1 (ko) 2015-10-08 2025-11-05 프레지던트 앤드 펠로우즈 오브 하바드 칼리지 다중화 게놈 편집
EP3365439A1 (en) 2015-10-20 2018-08-29 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
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
EP3443080B1 (en) 2016-04-13 2021-08-11 University of Massachusetts Repairing compound heterozygous recessive mutations by allele exchange
AU2017268458B2 (en) 2016-05-20 2022-07-21 Regeneron Pharmaceuticals, Inc. Methods for breaking immunological tolerance using multiple guide RNAS
WO2019148166A1 (en) 2018-01-29 2019-08-01 Massachusetts Institute Of Technology Methods of enhancing chromosomal homologous recombination

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
K. YOSHIMI ET AL, "Allele-specific genome editing and correction of disease-associated phenotypes in rats using the CRISPR-Cas platform", NATURE COMMUNICATIONS, (2014-06-26), vol. 5, doi:10.1038/ncomms5240 *

Also Published As

Publication number Publication date
RU2017121367A3 (cg-RX-API-DMAC7.html) 2019-11-05
WO2016081923A3 (en) 2016-07-07
US20200002730A1 (en) 2020-01-02
ES3013183T3 (en) 2025-04-11
SG11201703747RA (en) 2017-06-29
CN107208078A (zh) 2017-09-26
CA3176380A1 (en) 2016-05-26
KR102683423B1 (ko) 2024-07-10
KR102415093B1 (ko) 2022-07-04
KR20170102234A (ko) 2017-09-08
IL252181B (en) 2021-06-30
JP6727199B2 (ja) 2020-07-22
EP3521437B1 (en) 2025-01-15
CA2968440A1 (en) 2016-05-26
CN113444747A (zh) 2021-09-28
JP2020191880A (ja) 2020-12-03
KR102531016B1 (ko) 2023-05-10
RU2017121367A (ru) 2018-12-21
IL252181A0 (en) 2017-07-31
SMT201900354T1 (it) 2019-07-11
RU2020134412A (ru) 2020-11-11
EP3221457A2 (en) 2017-09-27
US20160145646A1 (en) 2016-05-26
PL3221457T3 (pl) 2019-09-30
US10457960B2 (en) 2019-10-29
JP7101211B2 (ja) 2022-07-14
HUE044907T2 (hu) 2019-11-28
US11697828B2 (en) 2023-07-11
MX2022000378A (es) 2022-02-10
ES2731437T3 (es) 2019-11-15
PT3221457T (pt) 2019-06-27
SI3221457T1 (sl) 2019-08-30
CY1121738T1 (el) 2020-07-31
HRP20190949T1 (hr) 2019-07-26
MX2017006670A (es) 2018-03-01
IL283585B2 (en) 2023-09-01
AU2015349692A1 (en) 2017-06-08
AU2021290301A1 (en) 2022-01-27
IL283585B1 (en) 2023-05-01
KR20230070319A (ko) 2023-05-22
LT3221457T (lt) 2019-06-10
RU2734770C2 (ru) 2020-10-23
KR20220093013A (ko) 2022-07-04
EP3221457B1 (en) 2019-03-20
RS58893B1 (sr) 2019-08-30
JP2017535271A (ja) 2017-11-30
US20230332185A1 (en) 2023-10-19
DK3221457T3 (da) 2019-06-03
SG10201913829YA (en) 2020-03-30
CN107208078B (zh) 2021-07-16
IL283585A (en) 2021-07-29
EP3521437C0 (en) 2025-01-15
AU2021290301B2 (en) 2024-02-29
EP3521437A1 (en) 2019-08-07
US20200002731A1 (en) 2020-01-02
NZ731962A (en) 2022-07-01
WO2016081923A2 (en) 2016-05-26
BR112017010547A2 (pt) 2018-02-27
CN113444747B (zh) 2025-02-11
IL301900A (en) 2023-06-01
MX389266B (es) 2025-03-20

Similar Documents

Publication Publication Date Title
AU2021290301B2 (en) METHODS AND COMPOSITIONS FOR TARGETED GENETIC MODIFICATION USING PAIRED GUIDE RNAs
KR102661748B1 (ko) 다중 가이드 RNAs를 이용한 면역학적 내성 파괴 방법
KR102530821B1 (ko) 단일 단계 다중 표적화를 통한 표적화된 유전자 변형을 위한 방법 및 조성물
HK40009103B (en) Methods for targeted genetic modification using paired guide rnas
HK40009103A (en) Methods for targeted genetic modification using paired guide rnas
HK1236222A1 (en) Methods and compositions for targeted genetic modification using paired guide rnas
HK1236222B (en) Methods and compositions for targeted genetic modification using paired guide rnas

Legal Events

Date Code Title Description
FGA Letters patent sealed or granted (standard patent)