JP6625971B2 - 配列操作のためのタンデムガイド系、方法および組成物の送達、エンジニアリングおよび最適化 - Google Patents

配列操作のためのタンデムガイド系、方法および組成物の送達、エンジニアリングおよび最適化 Download PDF

Info

Publication number
JP6625971B2
JP6625971B2 JP2016521449A JP2016521449A JP6625971B2 JP 6625971 B2 JP6625971 B2 JP 6625971B2 JP 2016521449 A JP2016521449 A JP 2016521449A JP 2016521449 A JP2016521449 A JP 2016521449A JP 6625971 B2 JP6625971 B2 JP 6625971B2
Authority
JP
Japan
Prior art keywords
sequence
tracr
cas9
composition
target
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
JP2016521449A
Other languages
English (en)
Japanese (ja)
Other versions
JP2016521993A5 (enExample
JP2016521993A (ja
Inventor
フェン チャン
フェン チャン
チェ ユ リン
チェ ユ リン
フェイ ラン
フェイ ラン
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.)
Massachusetts Institute of Technology
Broad Institute Inc
Original Assignee
Massachusetts Institute of Technology
Broad Institute 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 Massachusetts Institute of Technology, Broad Institute Inc filed Critical Massachusetts Institute of Technology
Publication of JP2016521993A publication Critical patent/JP2016521993A/ja
Publication of JP2016521993A5 publication Critical patent/JP2016521993A5/ja
Application granted granted Critical
Publication of JP6625971B2 publication Critical patent/JP6625971B2/ja
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N9/00Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
    • C12N9/14Hydrolases (3)
    • C12N9/16Hydrolases (3) acting on ester bonds (3.1)
    • C12N9/22Ribonucleases [RNase]; Deoxyribonucleases [DNase]
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09Recombinant DNA-technology
    • C12N15/87Introduction of foreign genetic material using processes not otherwise provided for, e.g. co-transformation
    • C12N15/90Stable introduction of foreign DNA into chromosome
    • C12N15/902Stable introduction of foreign DNA into chromosome using homologous recombination
    • C12N15/907Stable introduction of foreign DNA into chromosome using homologous recombination in mammalian cells
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09Recombinant DNA-technology
    • C12N15/10Processes for the isolation, preparation or purification of DNA or RNA
    • C12N15/102Mutagenizing nucleic acids
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09Recombinant DNA-technology
    • C12N15/10Processes for the isolation, preparation or purification of DNA or RNA
    • C12N15/1034Isolating an individual clone by screening libraries
    • C12N15/1082Preparation or screening gene libraries by chromosomal integration of polynucleotide sequences, HR-, site-specific-recombination, transposons, viral vectors
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09Recombinant DNA-technology
    • C12N15/63Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00Structure or type of the nucleic acid
    • C12N2310/10Type of nucleic acid
    • C12N2310/20Type of nucleic acid involving clustered regularly interspaced short palindromic repeats [CRISPR]
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00Structure or type of the nucleic acid
    • C12N2310/30Chemical structure
    • C12N2310/35Nature of the modification
    • C12N2310/351Conjugate
    • C12N2310/3519Fusion with another nucleic acid
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2800/00Nucleic acids vectors
    • C12N2800/80Vectors containing sites for inducing double-stranded breaks, e.g. meganuclease restriction sites

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Wood Science & Technology (AREA)
  • Zoology (AREA)
  • Biotechnology (AREA)
  • General Engineering & Computer Science (AREA)
  • Biomedical Technology (AREA)
  • Molecular Biology (AREA)
  • General Health & Medical Sciences (AREA)
  • Microbiology (AREA)
  • Biochemistry (AREA)
  • Biophysics (AREA)
  • Plant Pathology (AREA)
  • Physics & Mathematics (AREA)
  • Crystallography & Structural Chemistry (AREA)
  • Medicinal Chemistry (AREA)
  • Virology (AREA)
  • Bioinformatics & Computational Biology (AREA)
  • Mycology (AREA)
  • Cell Biology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Enzymes And Modification Thereof (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Breeding Of Plants And Reproduction By Means Of Culturing (AREA)
JP2016521449A 2013-06-17 2014-06-10 配列操作のためのタンデムガイド系、方法および組成物の送達、エンジニアリングおよび最適化 Active JP6625971B2 (ja)

Applications Claiming Priority (15)

Application Number Priority Date Filing Date Title
US201361836123P 2013-06-17 2013-06-17
US61/836,123 2013-06-17
US201361847537P 2013-07-17 2013-07-17
US61/847,537 2013-07-17
US201361862355P 2013-08-05 2013-08-05
US201361862468P 2013-08-05 2013-08-05
US61/862,355 2013-08-05
US61/862,468 2013-08-05
US201361871301P 2013-08-28 2013-08-28
US61/871,301 2013-08-28
US201361915407P 2013-12-12 2013-12-12
US61/915,407 2013-12-12
US201461979942P 2014-04-15 2014-04-15
US61/979,942 2014-04-15
PCT/US2014/041800 WO2014204724A1 (en) 2013-06-17 2014-06-10 Delivery, engineering and optimization of tandem guide systems, methods and compositions for sequence manipulation

Related Child Applications (1)

Application Number Title Priority Date Filing Date
JP2019215361A Division JP2020054354A (ja) 2013-06-17 2019-11-28 配列操作のためのタンデムガイド系、方法および組成物の送達、エンジニアリングおよび最適化

Publications (3)

Publication Number Publication Date
JP2016521993A JP2016521993A (ja) 2016-07-28
JP2016521993A5 JP2016521993A5 (enExample) 2019-10-03
JP6625971B2 true JP6625971B2 (ja) 2019-12-25

Family

ID=51059658

Family Applications (2)

Application Number Title Priority Date Filing Date
JP2016521449A Active JP6625971B2 (ja) 2013-06-17 2014-06-10 配列操作のためのタンデムガイド系、方法および組成物の送達、エンジニアリングおよび最適化
JP2019215361A Pending JP2020054354A (ja) 2013-06-17 2019-11-28 配列操作のためのタンデムガイド系、方法および組成物の送達、エンジニアリングおよび最適化

Family Applications After (1)

Application Number Title Priority Date Filing Date
JP2019215361A Pending JP2020054354A (ja) 2013-06-17 2019-11-28 配列操作のためのタンデムガイド系、方法および組成物の送達、エンジニアリングおよび最適化

Country Status (10)

Country Link
US (2) US11008588B2 (enExample)
EP (2) EP3011029B1 (enExample)
JP (2) JP6625971B2 (enExample)
KR (1) KR20160044457A (enExample)
CN (1) CN106062197A (enExample)
AU (1) AU2014281026B2 (enExample)
CA (1) CA2915834A1 (enExample)
DK (1) DK3011029T3 (enExample)
ES (1) ES2777217T3 (enExample)
WO (1) WO2014204724A1 (enExample)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US12447213B2 (en) 2016-10-07 2025-10-21 The Broad Institute, Inc. Modulation of novel immune checkpoint targets

Families Citing this family (300)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CA2853829C (en) 2011-07-22 2023-09-26 President And Fellows Of Harvard College Evaluation and improvement of nuclease cleavage specificity
US10266850B2 (en) 2012-05-25 2019-04-23 The Regents Of The University Of California Methods and compositions for RNA-directed target DNA modification and for RNA-directed modulation of transcription
KR20230065381A (ko) * 2012-07-25 2023-05-11 더 브로드 인스티튜트, 인코퍼레이티드 유도 dna 결합 단백질 및 게놈 교란 도구 및 이의 적용
CN110669758A (zh) 2012-10-23 2020-01-10 基因工具股份有限公司 用于切割靶dna 的组合物及其用途
EP3434776A1 (en) 2012-12-12 2019-01-30 The Broad Institute, Inc. Methods, models, systems, and apparatus for identifying target sequences for cas enzymes or crispr-cas systems for target sequences and conveying results thereof
WO2014093701A1 (en) 2012-12-12 2014-06-19 The Broad Institute, Inc. Functional genomics using crispr-cas systems, compositions, methods, knock out libraries and applications thereof
EP4234696A3 (en) 2012-12-12 2023-09-06 The Broad Institute Inc. Crispr-cas component systems, methods and compositions for sequence manipulation
RU2721275C2 (ru) 2012-12-12 2020-05-18 Те Брод Инститьют, Инк. Доставка, конструирование и оптимизация систем, способов и композиций для манипуляции с последовательностями и применения в терапии
US10760064B2 (en) 2013-03-15 2020-09-01 The General Hospital Corporation RNA-guided targeting of genetic and epigenomic regulatory proteins to specific genomic loci
KR102271291B1 (ko) 2013-03-15 2021-07-02 더 제너럴 하스피탈 코포레이션 특정 게놈 좌위에 대한 유전적 및 후성적 조절 단백질의 rna-안내 표적화
LT2986729T (lt) 2013-04-16 2018-10-25 Regeneron Pharmaceuticals, Inc. Žiurkės genomo tikslinė modifikacija
WO2014204729A1 (en) * 2013-06-17 2014-12-24 The Broad Institute Inc. Delivery, use and therapeutic applications of the crispr-cas systems and compositions for targeting disorders and diseases using viral components
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
BR112015031608A2 (pt) 2013-06-17 2017-08-22 Massachusetts Inst Technology Aplicação e uso dos sistemas crispr-cas, vetores e composições para direcionamento e terapia hepáticos
CA2915837A1 (en) 2013-06-17 2014-12-24 The Broad Institute, Inc. Optimized crispr-cas double nickase systems, methods and compositions for sequence manipulation
EP3725885A1 (en) 2013-06-17 2020-10-21 The Broad Institute, Inc. Functional genomics using crispr-cas systems, compositions methods, screens and applications thereof
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
US9526784B2 (en) 2013-09-06 2016-12-27 President And Fellows Of Harvard College Delivery system for functional nucleases
US9322037B2 (en) 2013-09-06 2016-04-26 President And Fellows Of Harvard College Cas9-FokI fusion proteins and uses thereof
US9340800B2 (en) 2013-09-06 2016-05-17 President And Fellows Of Harvard College Extended DNA-sensing GRNAS
ES3013744T3 (en) 2013-09-18 2025-04-15 Kymab Ltd Methods, cells and organisms
WO2015065964A1 (en) 2013-10-28 2015-05-07 The Broad Institute Inc. Functional genomics using crispr-cas systems, compositions, methods, screens and applications thereof
WO2015066119A1 (en) 2013-10-30 2015-05-07 North Carolina State University Compositions and methods related to a type-ii crispr-cas system in lactobacillus buchneri
EP3066201B1 (en) 2013-11-07 2018-03-07 Editas Medicine, Inc. Crispr-related methods and compositions with governing grnas
CN110951779B (zh) 2013-12-11 2024-04-16 瑞泽恩制药公司 用于靶向修饰基因组的方法和组合物
US9840699B2 (en) 2013-12-12 2017-12-12 President And Fellows Of Harvard College Methods for nucleic acid 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
EP3080257A1 (en) 2013-12-12 2016-10-19 The Broad Institute Inc. Compositions and methods of use of crispr-cas systems in nucleotide repeat disorders
MX374529B (es) * 2013-12-12 2025-03-06 Broad Inst Inc Suministro, uso y aplicaciones terapeuticas de sistemas y composiciones crispr-cas para edicion del genoma.
WO2015089364A1 (en) 2013-12-12 2015-06-18 The Broad Institute Inc. Crystal structure of a crispr-cas system, and uses thereof
EP3080261B1 (en) 2013-12-12 2019-05-22 The Broad Institute, Inc. Delivery, use and therapeutic applications of the crispr-cas systems and compositions for hbv and viral diseases and disorders
WO2015089486A2 (en) 2013-12-12 2015-06-18 The Broad Institute Inc. Systems, methods and compositions for sequence manipulation with optimized functional crispr-cas systems
US10787654B2 (en) 2014-01-24 2020-09-29 North Carolina State University Methods and compositions for sequence guiding Cas9 targeting
AU2015222944A1 (en) 2014-02-27 2016-09-08 Massachusetts Institute Of Technology T cell balance gene expression, compositions of matters and methods of use thereof
JP2017512481A (ja) 2014-04-08 2017-05-25 ノースカロライナ ステート ユニバーシティーNorth Carolina State University Crispr関連遺伝子を用いた、rna依存性の転写抑制のための方法および組成物
WO2016022363A2 (en) 2014-07-30 2016-02-11 President And Fellows Of Harvard College Cas9 proteins including ligand-dependent inteins
EP3180426B1 (en) 2014-08-17 2019-12-25 The Broad Institute, Inc. Genome editing using cas9 nickases
US10450584B2 (en) 2014-08-28 2019-10-22 North Carolina State University Cas9 proteins and guiding features for DNA targeting and genome editing
WO2016049251A1 (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 mutations in leukocytes
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
CA2963693A1 (en) 2014-10-10 2016-04-14 Editas Medicine, Inc. Compositions and methods for promoting homology directed repair
DK3207124T3 (da) 2014-10-15 2019-08-12 Regeneron Pharma Fremgangsmåder og sammensætninger til generering eller bevaring af pluripotente celler
US20170247762A1 (en) 2014-10-27 2017-08-31 The Board Institute Inc. Compositions, methods and use of synthetic lethal screening
US10725041B2 (en) * 2014-11-04 2020-07-28 Versiti Blood Research Institute Foundation, Inc. Method to bioengineer designer platelets using gene editing and stem cell methodologies
AU2015342749B2 (en) 2014-11-07 2022-01-27 Editas Medicine, Inc. Methods for improving CRISPR/Cas-mediated genome-editing
CA3176380A1 (en) 2014-11-21 2016-05-26 Regeneron Pharmaceuticals, Inc. Methods and compositions for targeted genetic modification using paired guide rnas
EP3224381B1 (en) 2014-11-25 2019-09-04 The Brigham and Women's Hospital, Inc. Method of identifying a person having a predisposition to or afflicted with a cardiometabolic disease
CA2969619A1 (en) 2014-12-03 2016-06-09 Agilent Technologies, Inc. Guide rna with chemical modifications
JP6830437B2 (ja) 2014-12-10 2021-02-17 リージェンツ オブ ザ ユニバーシティ オブ ミネソタ 疾患を処置するための遺伝子改変された細胞、組織および臓器
EP3230452B1 (en) 2014-12-12 2025-06-11 The Broad Institute, Inc. Dead guides for crispr transcription factors
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)
EP3985115A1 (en) 2014-12-12 2022-04-20 The Broad Institute, Inc. Protected guide rnas (pgrnas)
WO2016094874A1 (en) 2014-12-12 2016-06-16 The Broad Institute Inc. Escorted and functionalized guides for crispr-cas systems
WO2016100974A1 (en) 2014-12-19 2016-06-23 The Broad Institute Inc. Unbiased identification of double-strand breaks and genomic rearrangement by genome-wide insert capture sequencing
WO2016106236A1 (en) 2014-12-23 2016-06-30 The Broad Institute Inc. Rna-targeting system
EP3702456A1 (en) 2014-12-24 2020-09-02 The Broad Institute, Inc. Crispr having or associated with destabilization domains
WO2016108926A1 (en) 2014-12-30 2016-07-07 The Broad Institute Inc. Crispr mediated in vivo modeling and genetic screening of tumor growth and metastasis
US11339399B2 (en) 2014-12-31 2022-05-24 Viridos, Inc. Compositions and methods for high efficiency in vivo genome editing
RU2713328C2 (ru) * 2015-01-28 2020-02-04 Пайонир Хай-Бред Интернэшнл, Инк. Гибридные днк/рнк-полинуклеотиды crispr и способы применения
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
EP3262193A2 (en) 2015-02-26 2018-01-03 The Broad Institute Inc. T cell balance gene expression, compositions of matters and methods of use thereof
US9944912B2 (en) 2015-03-03 2018-04-17 The General Hospital Corporation Engineered CRISPR-Cas9 nucleases with altered PAM specificity
AU2016246450B2 (en) 2015-04-06 2022-03-17 Agilent Technologies, Inc. Chemically modified guide RNAs for CRISPR/Cas-mediated gene regulation
GB201506509D0 (en) 2015-04-16 2015-06-03 Univ Wageningen Nuclease-mediated genome editing
WO2016182893A1 (en) 2015-05-08 2016-11-17 Teh Broad Institute Inc. Functional genomics using crispr-cas systems for saturating mutagenesis of non-coding elements, compositions, methods, libraries and applications thereof
EP3294896A1 (en) 2015-05-11 2018-03-21 Editas Medicine, Inc. Optimized crispr/cas9 systems and methods for gene editing in stem cells
AU2016265255B2 (en) * 2015-05-16 2022-03-17 Genzyme Corporation Gene editing of deep intronic mutations
US10136649B2 (en) 2015-05-29 2018-11-27 North Carolina State University Methods for screening bacteria, archaea, algae, and yeast using CRISPR nucleic acids
EP3302709B1 (en) 2015-06-01 2021-05-19 Temple University - Of The Commonwealth System of Higher Education Methods and compositions for rna-guided treatment of hiv infection
KR102796744B1 (ko) 2015-06-09 2025-04-15 에디타스 메디신, 인코포레이티드 이식의 개선을 위한 crispr/cas-관련 방법 및 조성물
CN115537421A (zh) 2015-06-15 2022-12-30 北卡罗来纳州立大学 有效递送核酸和基于rna的抗微生物剂的方法和组合物
WO2016205728A1 (en) 2015-06-17 2016-12-22 Massachusetts Institute Of Technology Crispr mediated recording of cellular events
WO2016205613A1 (en) 2015-06-18 2016-12-22 The Broad Institute Inc. Crispr enzyme mutations reducing off-target effects
WO2016205749A1 (en) * 2015-06-18 2016-12-22 The Broad Institute Inc. Novel crispr enzymes and systems
CA3012631A1 (en) 2015-06-18 2016-12-22 The Broad Institute Inc. Novel crispr enzymes and systems
US10648020B2 (en) 2015-06-18 2020-05-12 The Broad Institute, Inc. CRISPR enzymes and systems
WO2016205745A2 (en) * 2015-06-18 2016-12-22 The Broad Institute Inc. Cell sorting
US9790490B2 (en) 2015-06-18 2017-10-17 The Broad Institute Inc. CRISPR enzymes and systems
WO2016205759A1 (en) 2015-06-18 2016-12-22 The Broad Institute Inc. Engineering and optimization of systems, methods, enzymes and guide scaffolds of cas9 orthologs and variants for sequence manipulation
EP4545544A3 (en) 2015-06-29 2025-10-08 Ionis Pharmaceuticals, Inc. Modified crispr rna and modified single crispr rna and uses thereof
CA2993431A1 (en) 2015-07-31 2017-02-09 Regents Of The University Of Minnesota Nuclease based knockouts of immunological checkpoint genes in immune cells
US20180230450A1 (en) * 2015-08-03 2018-08-16 President And Fellows Of Harvard College Cas9 Genome Editing and Transcriptional Regulation
EP4512819A3 (en) 2015-08-12 2025-08-06 The General Hospital Corporation Compositions and methods that promote hypoxia or the hypoxia response for treatment and prevention of mitochondrial dysfunction and oxidative stress disorders
US11214800B2 (en) 2015-08-18 2022-01-04 The Broad Institute, Inc. Methods and compositions for altering function and structure of chromatin loops and/or domains
US9926546B2 (en) 2015-08-28 2018-03-27 The General Hospital Corporation Engineered CRISPR-Cas9 nucleases
US9512446B1 (en) 2015-08-28 2016-12-06 The General Hospital Corporation Engineered CRISPR-Cas9 nucleases
JP6799058B2 (ja) 2015-09-21 2020-12-09 アークトゥラス・セラピューティクス・インコーポレイテッドArcturus Therapeutics,Inc. アレル選択的な遺伝子編集およびその使用
CA2999500A1 (en) 2015-09-24 2017-03-30 Editas Medicine, Inc. Use of exonucleases to improve crispr/cas-mediated genome editing
WO2017058751A1 (en) 2015-09-28 2017-04-06 North Carolina State University Methods and compositions for sequence specific antimicrobials
WO2017069958A2 (en) 2015-10-09 2017-04-27 The Brigham And Women's Hospital, Inc. Modulation of novel immune checkpoint targets
AU2016342038B2 (en) 2015-10-22 2022-09-08 Massachusetts Institute Of Technology Type VI-B CRISPR enzymes and systems
IL294014B2 (en) 2015-10-23 2024-07-01 Harvard College Nucleobase editors and uses thereof
EP3368687B1 (en) 2015-10-27 2021-09-29 The Broad Institute, Inc. Compositions and methods for targeting cancer-specific sequence variations
WO2017075465A1 (en) 2015-10-28 2017-05-04 The Broad Institute Inc. Compositions and methods for evaluating and modulating immune responses by detecting and targeting gata3
WO2017075294A1 (en) 2015-10-28 2017-05-04 The Board Institute Inc. Assays for massively combinatorial perturbation profiling and cellular circuit reconstruction
EP3368689B1 (en) 2015-10-28 2020-06-17 The Broad Institute, Inc. Composition for modulating immune responses by use of immune cell gene signature
WO2017075451A1 (en) 2015-10-28 2017-05-04 The Broad Institute Inc. Compositions and methods for evaluating and modulating immune responses by detecting and targeting pou2af1
US11092607B2 (en) 2015-10-28 2021-08-17 The Board Institute, Inc. Multiplex analysis of single cell constituents
US11001622B2 (en) 2015-11-19 2021-05-11 The Brigham And Women's Hospital, Inc. Method of treating autoimmune disease with lymphocyte antigen CD5-like (CD5L) protein
WO2017106657A1 (en) 2015-12-18 2017-06-22 The Broad Institute Inc. Novel crispr enzymes and systems
US11542466B2 (en) 2015-12-22 2023-01-03 North Carolina State University Methods and compositions for delivery of CRISPR based antimicrobials
EP4219689A3 (en) 2015-12-30 2023-12-20 Novartis AG Immune effector cell therapies with enhanced efficacy
CA3012042A1 (en) * 2016-01-26 2017-08-03 Cedars-Sinai Medical Center Systems and methods for in vivo dual recombinase-mediated cassette exchange (drmce) and disease models thereof
WO2017147196A1 (en) 2016-02-22 2017-08-31 Massachusetts Institute Of Technology Methods for identifying and modulating immune phenotypes
US11427861B2 (en) 2016-03-17 2022-08-30 Massachusetts Institute Of Technology Methods for identifying and modulating co-occurant cellular phenotypes
EP3219799A1 (en) 2016-03-17 2017-09-20 IMBA-Institut für Molekulare Biotechnologie GmbH Conditional crispr sgrna expression
US11597924B2 (en) 2016-03-25 2023-03-07 Editas Medicine, Inc. Genome editing systems comprising repair-modulating enzyme molecules and methods of their use
EP3443086B1 (en) 2016-04-13 2021-11-24 Editas Medicine, Inc. Cas9 fusion molecules, gene editing systems, and methods of use thereof
CA3026055A1 (en) 2016-04-19 2017-10-26 The Broad Institute, Inc. Novel crispr enzymes and systems
US11286478B2 (en) 2016-04-19 2022-03-29 The Broad Institute, Inc. Cpf1 complexes with reduced indel activity
US20200263190A1 (en) * 2016-04-19 2020-08-20 The Broad Institute, Inc. Novel crispr enzymes and systems
CN109475109B (zh) 2016-05-20 2021-10-29 瑞泽恩制药公司 用于使用多个引导rna来破坏免疫耐受性的方法
US10767175B2 (en) 2016-06-08 2020-09-08 Agilent Technologies, Inc. High specificity genome editing using chemically modified guide RNAs
CN109642231A (zh) 2016-06-17 2019-04-16 博德研究所 Vi型crispr直向同源物和系统
AU2017295720B2 (en) 2016-07-13 2021-07-22 Vertex Pharmaceuticals Incorporated Methods, compositions and kits for increasing genome editing efficiency
JP7026304B2 (ja) * 2016-07-29 2022-02-28 マックス-プランク-ゲゼルシャフト ツア フェルデルンク デア ヴィッセンシャフテン エー.ファウ. 部位特異的dna開裂及び修復による標的化原位置タンパク質多様化
AU2017306676B2 (en) 2016-08-03 2024-02-22 President And Fellows Of Harvard College Adenosine nucleobase editors and uses thereof
EP3497214B1 (en) 2016-08-09 2023-06-28 President and Fellows of Harvard College Programmable cas9-recombinase fusion proteins and uses thereof
WO2018035364A1 (en) 2016-08-17 2018-02-22 The Broad Institute Inc. Product and methods useful for modulating and evaluating immune responses
US12431216B2 (en) 2016-08-17 2025-09-30 Broad Institute, Inc. Methods for identifying class 2 crispr-cas systems
EP3500670B1 (en) 2016-08-17 2024-07-10 The Broad Institute, Inc. Method for selecting target sequences for guide rna of crispr systems
EP4485466A3 (en) 2016-08-17 2025-04-02 The Broad Institute Inc. Novel crispr enzymes and systems
EP3500677A4 (en) * 2016-08-20 2020-04-01 Avellino Lab USA, Inc. Single guide rna, crispr/cas9 systems, and methods of use 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
US20190262399A1 (en) 2016-09-07 2019-08-29 The Broad Institute, Inc. Compositions and methods for evaluating and modulating immune responses
US12188059B2 (en) 2016-09-13 2025-01-07 The Broad Institute, Inc. Proximity-dependent biotinylation and uses thereof
US20190225974A1 (en) 2016-09-23 2019-07-25 BASF Agricultural Solutions Seed US LLC Targeted genome optimization in plants
EP3516056B1 (en) * 2016-09-23 2024-11-27 DSM IP Assets B.V. A guide-rna expression system for a host cell
WO2018064208A1 (en) 2016-09-28 2018-04-05 The Broad Institute, Inc. Systematic screening and mapping of regulatory elements in non-coding genomic regions, methods, compositions, and applications thereof
WO2018071868A1 (en) 2016-10-14 2018-04-19 President And Fellows Of Harvard College Aav delivery of nucleobase editors
EP4338799A3 (en) 2016-10-18 2024-06-05 Regents of the University of Minnesota Tumor infiltrating lymphocytes and methods of therapy
WO2018083606A1 (en) 2016-11-01 2018-05-11 Novartis Ag Methods and compositions for enhancing gene editing
US12227578B2 (en) 2016-11-11 2025-02-18 The Broad Institute, Inc. Modulation of intestinal epithelial cell differentiation, maintenance and/or function through T cell action
WO2018088694A2 (ko) 2016-11-14 2018-05-17 주식회사 툴젠 인위적으로 조작된 sc 기능 조절 시스템
WO2018107103A1 (en) 2016-12-09 2018-06-14 The Broad Institute, Inc. Crispr-systems for modifying a trait of interest in a plant
EP3555297A1 (en) 2016-12-19 2019-10-23 Editas Medicine, Inc. Assessing nuclease cleavage
WO2018119359A1 (en) 2016-12-23 2018-06-28 President And Fellows Of Harvard College Editing of ccr5 receptor gene to protect against hiv infection
WO2018129486A2 (en) * 2017-01-06 2018-07-12 President And Fellows Of Harvard College Composition and methods for enhanced knock-in reporter gene expression
EP3565907B1 (en) 2017-01-06 2022-05-04 Editas Medicine, Inc. Methods of assessing nuclease cleavage
TW201839136A (zh) 2017-02-06 2018-11-01 瑞士商諾華公司 治療血色素異常症之組合物及方法
WO2018148511A1 (en) * 2017-02-10 2018-08-16 Zymergen Inc. A modular universal plasmid design strategy for the assembly and editing of multiple dna constructs for multiple hosts
GB201702847D0 (en) * 2017-02-22 2017-04-05 Cancer Res Tech Ltd Cell labelling, tracking and retrieval
WO2018165631A1 (en) 2017-03-09 2018-09-13 President And Fellows Of Harvard College Cancer vaccine
EP3592853A1 (en) 2017-03-09 2020-01-15 President and Fellows of Harvard College Suppression of pain by gene editing
WO2018165629A1 (en) 2017-03-10 2018-09-13 President And Fellows Of Harvard College Cytosine to guanine base editor
EP3596207B1 (en) 2017-03-15 2023-12-20 The Broad Institute, Inc. Novel cas13b orthologues crispr enzymes and systems
WO2018170515A1 (en) 2017-03-17 2018-09-20 The Broad Institute, Inc. Methods for identifying and modulating co-occurant cellular phenotypes
KR20240116572A (ko) 2017-03-23 2024-07-29 프레지던트 앤드 펠로우즈 오브 하바드 칼리지 핵산 프로그램가능한 dna 결합 단백질을 포함하는 핵염기 편집제
WO2018175924A1 (en) 2017-03-24 2018-09-27 The Broad Institute, Inc. Methods and compositions for regulating innate lymphoid cell inflammatory responses
CA3050616A1 (en) * 2017-03-24 2018-09-27 Curevac Ag Nucleic acids encoding crispr-associated proteins and uses thereof
US11963966B2 (en) 2017-03-31 2024-04-23 Dana-Farber Cancer Institute, Inc. Compositions and methods for treating ovarian tumors
WO2018183921A1 (en) 2017-04-01 2018-10-04 The Broad Institute, Inc. Methods and compositions for detecting and modulating an immunotherapy resistance gene signature in cancer
KR20240155360A (ko) 2017-04-12 2024-10-28 더 브로드 인스티튜트, 인코퍼레이티드 신규 타입 vi crispr 오르소로그 및 시스템
US12331319B2 (en) 2017-04-12 2025-06-17 The Broad Institute, Inc. Respiratory and sweat gland ionocytes
US20200071773A1 (en) 2017-04-12 2020-03-05 Massachusetts Eye And Ear Infirmary Tumor signature for metastasis, compositions of matter methods of use thereof
US12350368B2 (en) 2017-04-14 2025-07-08 The Broad Institute, Inc. Delivery of large payloads
MX2019012398A (es) 2017-04-18 2020-09-25 Broad Inst Inc Composiciones para detectar secreciones y metodos de uso.
EP3612232A1 (en) 2017-04-21 2020-02-26 The Broad Institute, Inc. Targeted delivery to beta cells
EP3615672A1 (en) 2017-04-28 2020-03-04 Editas Medicine, Inc. Methods and systems for analyzing guide rna molecules
WO2018204777A2 (en) 2017-05-05 2018-11-08 The Broad Institute, Inc. Methods for identification and modification of lncrna associated with target genotypes and phenotypes
EP3622092A4 (en) 2017-05-11 2021-06-23 The Broad Institute, Inc. METHODS AND COMPOSITIONS OF USE OF CD8 + TUMOR-INFILTRATING LYMPHOCYTE SUBTYPES AND GENE SIGNATURES THEREOF
US11560566B2 (en) 2017-05-12 2023-01-24 President And Fellows Of Harvard College Aptazyme-embedded guide RNAs for use with CRISPR-Cas9 in genome editing and transcriptional activation
CA3063739A1 (en) 2017-05-18 2018-11-22 The Broad Institute, Inc. Systems, methods, and compositions for targeted nucleic acid editing
EP3625342B1 (en) 2017-05-18 2022-08-24 The Broad Institute, Inc. Systems, methods, and compositions for targeted nucleic acid editing
EP3630975B1 (en) * 2017-05-26 2025-11-19 North Carolina State University Altered guide rnas for modulating cas9 activity and methods of use
US11603544B2 (en) 2017-06-05 2023-03-14 Fred Hutchinson Cancer Center Genomic safe harbors for genetic therapies in human stem cells and engineered nanoparticles to provide targeted genetic therapies
CA3065813A1 (en) 2017-06-09 2018-12-13 Editas Medicine, Inc. Engineered cas9 nucleases
US11897953B2 (en) 2017-06-14 2024-02-13 The Broad Institute, Inc. Compositions and methods targeting complement component 3 for inhibiting tumor growth
JP7454494B2 (ja) 2017-06-26 2024-03-22 ザ・ブロード・インスティテュート・インコーポレイテッド 標的化された核酸編集のためのcrispr/cas-アデニンデアミナーゼ系の組成物、系及び方法
EP3645721A1 (en) 2017-06-30 2020-05-06 Novartis AG Methods for the treatment of disease with gene editing systems
EP3645021A4 (en) 2017-06-30 2021-04-21 Intima Bioscience, Inc. ADENO-ASSOCIATED VIRAL VECTORS FOR GENE THERAPY
SG11202000145XA (en) * 2017-07-12 2020-02-27 Refuge Biotechnologies Inc Methods and systems for conditionally regulating gene expression
WO2019014581A1 (en) 2017-07-14 2019-01-17 The Broad Institute, Inc. METHODS AND COMPOSITIONS FOR MODULATING THE ACTIVITY OF A CYTOTOXIC LYMPHOCYTE
EP3652312A1 (en) 2017-07-14 2020-05-20 Editas Medicine, Inc. Systems and methods for targeted integration and genome editing and detection thereof using integrated priming sites
WO2019018440A1 (en) 2017-07-17 2019-01-24 The Broad Institute, Inc. HUMAN COLON CELL ATLAS IN GOOD HEALTH AND WITH HEMORRHAGIC RECTO-COLITIS
WO2019018694A1 (en) 2017-07-19 2019-01-24 Dana-Farber Cancer Institute, Inc. DIAGNOSIS AND TREATMENT OF CANCER
CN111801345A (zh) 2017-07-28 2020-10-20 哈佛大学的校长及成员们 使用噬菌体辅助连续进化(pace)的进化碱基编辑器的方法和组合物
EP3663310A4 (en) 2017-08-04 2021-08-11 Peking University TALE RVD SPECIFICALLY RECOGNIZING A DNA BASE MODIFIED BY METHYLATION AND CORRESPONDING APPLICATION
WO2019028686A1 (zh) 2017-08-08 2019-02-14 北京大学 基因敲除方法
CN111278450B (zh) 2017-08-23 2024-04-09 通用医疗公司 具有改变的PAM特异性的工程化的CRISPR-Cas9核酸酶
US11319532B2 (en) 2017-08-30 2022-05-03 President And Fellows Of Harvard College High efficiency base editors comprising Gam
WO2019060746A1 (en) 2017-09-21 2019-03-28 The Broad Institute, Inc. SYSTEMS, METHODS, AND COMPOSITIONS FOR THE TARGETED EDITING OF NUCLEIC ACIDS
WO2019070755A1 (en) 2017-10-02 2019-04-11 The Broad Institute, Inc. METHODS AND COMPOSITIONS FOR DETECTING AND MODULATING A GENETIC SIGNATURE OF IMMUNOTHERAPY RESISTANCE IN CANCER
US20200255828A1 (en) 2017-10-04 2020-08-13 The Broad Institute, Inc. Methods and compositions for altering function and structure of chromatin loops and/or domains
WO2019079362A1 (en) 2017-10-16 2019-04-25 Massachusetts Institute Of Technology HOST-PATHOGENIC INTERACTION OF MYCOBACTERIUM TUBERCULOSIS
WO2019079347A1 (en) 2017-10-16 2019-04-25 The Broad Institute, Inc. USES OF BASIC EDITORS ADENOSINE
AU2018351072B9 (en) 2017-10-20 2024-09-05 Fred Hutchinson Cancer Center Systems and methods to produce B cells genetically modified to express selected antibodies
WO2019135816A2 (en) 2017-10-23 2019-07-11 The Broad Institute, Inc. Novel nucleic acid modifiers
WO2019089803A1 (en) 2017-10-31 2019-05-09 The Broad Institute, Inc. Methods and compositions for studying cell evolution
US20210180053A1 (en) 2017-11-01 2021-06-17 Novartis Ag Synthetic rnas and methods of use
WO2019094955A1 (en) 2017-11-13 2019-05-16 The Broad Institute, Inc. Methods and compositions for targeting developmental and oncogenic programs in h3k27m gliomas
WO2019094984A1 (en) 2017-11-13 2019-05-16 The Broad Institute, Inc. Methods for determining spatial and temporal gene expression dynamics during adult neurogenesis in single cells
AU2018372763A1 (en) 2017-11-21 2020-05-28 Bayer Healthcare Llc Materials and methods for treatment of autosomal dominant Retinitis Pigmentosa
WO2019113506A1 (en) 2017-12-07 2019-06-13 The Broad Institute, Inc. Methods and compositions for multiplexing single cell and single nuclei sequencing
US12406749B2 (en) 2017-12-15 2025-09-02 The Broad Institute, Inc. Systems and methods for predicting repair outcomes in genetic engineering
US11994512B2 (en) 2018-01-04 2024-05-28 Massachusetts Institute Of Technology Single-cell genomic methods to generate ex vivo cell systems that recapitulate in vivo biology with improved fidelity
CN111741955B (zh) 2018-01-17 2024-02-23 沃泰克斯药物股份有限公司 Dna-pk抑制剂
EP3740483B1 (en) 2018-01-17 2023-01-11 Vertex Pharmaceuticals Incorporated Quinoxalinone compounds, compositions, methods, and kits for increasing genome editing efficiency
WO2019143678A1 (en) 2018-01-17 2019-07-25 Vertex Pharmaceuticals Incorporated Dna-pk inhibitors
WO2019178550A1 (en) 2018-03-16 2019-09-19 Cedars-Sinai Medical Center Methods and compositions for inducible expression of neurotrophic factors
CN108424934A (zh) * 2018-04-16 2018-08-21 和元生物技术(上海)股份有限公司 一种慢病毒cag-cmv双启动子改造载体构建及应用
WO2019204585A1 (en) 2018-04-19 2019-10-24 Massachusetts Institute Of Technology Single-stranded break detection in double-stranded dna
ES2922902T3 (es) 2018-04-24 2022-09-21 Kws Saat Se & Co Kgaa Plantas con digestibilidad mejorada y haplotipos marcadores
US11957695B2 (en) 2018-04-26 2024-04-16 The Broad Institute, Inc. Methods and compositions targeting glucocorticoid signaling for modulating immune responses
US12281301B2 (en) 2018-04-27 2025-04-22 The Broad Institute, Inc. Sequencing-based proteomics
US20210386829A1 (en) 2018-05-04 2021-12-16 The Broad Institute, Inc. Compositions and methods for modulating cgrp signaling to regulate innate lymphoid cell inflammatory responses
EP3797160A1 (en) 2018-05-23 2021-03-31 The Broad Institute Inc. Base editors and uses thereof
US20210371932A1 (en) 2018-06-01 2021-12-02 Massachusetts Institute Of Technology Methods and compositions for detecting and modulating microenvironment gene signatures from the csf of metastasis patients
EP3578658A1 (en) 2018-06-08 2019-12-11 Johann Wolfgang Goethe-Universität Frankfurt Method for generating a gene editing vector with fixed guide rna pairs
CN108846258B (zh) * 2018-06-08 2021-05-18 中国人民解放军军事科学院军事医学研究院 一种自动检测分节段rna病毒重配的方法
US12036240B2 (en) 2018-06-14 2024-07-16 The Broad Institute, Inc. Compositions and methods targeting complement component 3 for inhibiting tumor growth
WO2019237399A1 (zh) * 2018-06-16 2019-12-19 深圳市博奥康生物科技有限公司 CRISPR-Cas9特异性敲除人C2orf40基因的方法及其特异的sgRNA
WO2020006049A1 (en) 2018-06-26 2020-01-02 The Broad Institute, Inc. Crispr/cas and transposase based amplification compositions, systems and methods
AU2019294630A1 (en) 2018-06-26 2020-12-17 Massachusetts Institute Of Technology Crispr effector system based amplification methods, systems, and diagnostics
EP3823633A4 (en) 2018-06-29 2023-05-03 Editas Medicine, Inc. SYNTHETIC LEAD MOLECULES, COMPOSITIONS AND METHODS RELATED THERETO
WO2020014261A1 (en) 2018-07-09 2020-01-16 The Broad Institute, Inc. Rna programmable epigenetic rna modifiers and uses thereof
AU2019314433A1 (en) 2018-07-31 2021-03-25 Massachusetts Institute Of Technology Novel CRISPR enzymes and systems
US20210163944A1 (en) 2018-08-07 2021-06-03 The Broad Institute, Inc. Novel cas12b enzymes and systems
US12421507B2 (en) 2018-08-20 2025-09-23 The Broad Institute, Inc. Methods and compositions for optochemical control of CRISPR-CAS9
WO2020041387A1 (en) 2018-08-20 2020-02-27 The Brigham And Women's Hospital, Inc. Degradation domain modifications for spatio-temporal control of rna-guided nucleases
US20210317479A1 (en) 2018-09-06 2021-10-14 The Broad Institute, Inc. Nucleic acid assemblies for use in targeted delivery
EP3849565A4 (en) 2018-09-12 2022-12-28 Fred Hutchinson Cancer Research Center REDUCTION OF CD33 EXPRESSION TO SELECTIVELY PROTECT THERAPEUTIC CELLS
AU2019343045A1 (en) 2018-09-18 2021-05-13 Vnv Newco Inc. ARC-based capsids and uses thereof
WO2020072254A1 (en) 2018-10-01 2020-04-09 North Carolina State University Recombinant type i crispr-cas system and uses thereof for killing target cells
US12203123B2 (en) 2018-10-01 2025-01-21 North Carolina State University Recombinant type I CRISPR-Cas system and uses thereof for screening for variant cells
US10711267B2 (en) 2018-10-01 2020-07-14 North Carolina State University Recombinant type I CRISPR-Cas system
WO2020072250A1 (en) 2018-10-01 2020-04-09 North Carolina State University Recombinant type i crispr-cas system and uses thereof for genome modification and alteration of expression
US20220411783A1 (en) 2018-10-12 2022-12-29 The Broad Institute, Inc. Method for extracting nuclei or whole cells from formalin-fixed paraffin-embedded tissues
US20210379057A1 (en) 2018-10-16 2021-12-09 Massachusetts Institute Of Technology Nutlin-3a for use in treating a mycobacterium tuberculosis infection
WO2020092453A1 (en) 2018-10-29 2020-05-07 The Broad Institute, Inc. Nucleobase editors comprising geocas9 and uses thereof
WO2020097360A1 (en) * 2018-11-07 2020-05-14 The Regents Of The University Of Colorado, A Body Corporate Methods and compositions for genome-wide analysis and use of genome cutting and repair
US12165743B2 (en) 2018-11-09 2024-12-10 The Broad Institute, Inc. Compressed sensing for screening and tissue imaging
WO2020131586A2 (en) 2018-12-17 2020-06-25 The Broad Institute, Inc. Methods for identifying neoantigens
US11384344B2 (en) 2018-12-17 2022-07-12 The Broad Institute, Inc. CRISPR-associated transposase systems and methods of use thereof
WO2020125762A1 (en) * 2018-12-20 2020-06-25 Peking University Compositions and methods for highly efficient genetic screening using barcoded guide rna constructs
CN111349654B (zh) * 2018-12-20 2023-01-24 北京大学 使用加标签的向导rna构建体进行高效基因筛选的组合物和方法
US11739156B2 (en) 2019-01-06 2023-08-29 The Broad Institute, Inc. Massachusetts Institute of Technology Methods and compositions for overcoming immunosuppression
WO2020154500A1 (en) 2019-01-23 2020-07-30 The Broad Institute, Inc. Supernegatively charged proteins and uses thereof
BR112021018607A2 (pt) 2019-03-19 2021-11-23 Massachusetts Inst Technology Métodos e composições para editar sequências de nucleotídeos
WO2020206036A1 (en) 2019-04-01 2020-10-08 The Broad Institute, Inc. Novel nucleic acid modifier
CN111812066B (zh) * 2019-04-10 2023-04-28 华东理工大学 基于CRISPR/Cas12a系统的生物传感器、试剂盒及其在小分子检测中的用途
EP3956349A1 (en) 2019-04-17 2022-02-23 The Broad Institute, Inc. Adenine base editors with reduced off-target effects
CN114096684B (zh) 2019-05-13 2024-11-19 科沃施种子欧洲股份两合公司 玉米的耐旱性
US20220235340A1 (en) 2019-05-20 2022-07-28 The Broad Institute, Inc. Novel crispr-cas systems and uses thereof
US20220220469A1 (en) 2019-05-20 2022-07-14 The Broad Institute, Inc. Non-class i multi-component nucleic acid targeting systems
AR118995A1 (es) 2019-05-25 2021-11-17 Kws Saat Se & Co Kgaa Mejorador de la inducción de haploides
WO2020243661A1 (en) 2019-05-31 2020-12-03 The Broad Institute, Inc. Methods for treating metabolic disorders by targeting adcy5
CN112168808B (zh) * 2019-07-02 2023-01-24 深圳市第二人民医院 一种基于crispr的细胞核靶向药物递送系统
BR112021026832A2 (pt) 2019-07-02 2022-05-10 Hutchinson Fred Cancer Res Vetores ad35 recombinantes e aprimoramentos da terapia gênica relacionada
EP4008784A1 (en) * 2019-08-01 2022-06-08 Astellas Pharma Inc. Guide rna for targeted-editing with functional base sequence added thereto
EP3772542A1 (en) 2019-08-07 2021-02-10 KWS SAAT SE & Co. KGaA Modifying genetic variation in crops by modulating the pachytene checkpoint protein 2
US20220298501A1 (en) 2019-08-30 2022-09-22 The Broad Institute, Inc. Crispr-associated mu transposase systems
CA3151563A1 (en) 2019-09-20 2021-03-25 Feng Zhang Novel type vi crispr enzymes and systems
CA3151690A1 (en) * 2019-09-23 2021-04-01 Beau WEBBER Genetically-edited immune cells and methods of therapy
US11981922B2 (en) 2019-10-03 2024-05-14 Dana-Farber Cancer Institute, Inc. Methods and compositions for the modulation of cell interactions and signaling in the tumor microenvironment
US12435330B2 (en) 2019-10-10 2025-10-07 The Broad Institute, Inc. Methods and compositions for prime editing RNA
WO2021074367A1 (en) 2019-10-17 2021-04-22 KWS SAAT SE & Co. KGaA Enhanced disease resistance of crops by downregulation of repressor genes
KR20220126725A (ko) * 2019-12-11 2022-09-16 인텔리아 테라퓨틱스, 인크. 유전자 편집을 위한 변형된 가이드 rna
US12264341B2 (en) 2020-01-24 2025-04-01 The General Hospital Corporation CRISPR-Cas enzymes with enhanced on-target activity
US12312613B2 (en) 2020-01-24 2025-05-27 The General Hospital Corporation Unconstrained genome targeting with near-PAMless engineered CRISPR-Cas9 variants
EP3872190A1 (en) 2020-02-26 2021-09-01 Antibodies-Online GmbH A method of using cut&run or cut&tag to validate crispr-cas targeting
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
AR122206A1 (es) 2020-05-29 2022-08-24 Kws Saat Se & Co Kgaa Inducción de haploides en plantas
KR20230036110A (ko) * 2020-06-12 2023-03-14 플래그쉽 파이어니어링 이노베이션스 브이, 인크. 탠덤 아넬로바이러스 구축물
CN111979266A (zh) * 2020-08-28 2020-11-24 江苏集萃药康生物科技有限公司 一种pcsk9人源化小鼠模型的构建方法及其应用
WO2022087269A1 (en) 2020-10-21 2022-04-28 Verint Americas Inc. System and method of automated determination of use of sensitive information and corrective action for improper use
EP4001429A1 (en) 2020-11-16 2022-05-25 Antibodies-Online GmbH Analysis of crispr-cas binding and cleavage sites followed by high-throughput sequencing (abc-seq)
CN114606196A (zh) * 2020-12-04 2022-06-10 南京大学 一种进行siRNA表达和体内递送的细胞疗法
CN112899306B (zh) * 2020-12-21 2023-06-30 南京启真基因工程有限公司 Crispr系统及其在构建gabrg2基因突变的克隆猪核供体细胞中的应用
AU2022216614A1 (en) 2021-02-05 2023-02-23 Christiana Care Gene Editing Institute, Inc. Methods of and compositions for reducing gene expression and/or activity
US11639520B2 (en) 2021-07-12 2023-05-02 Labsimply, Inc. Compositions of matter for detection assays
CN118368974A (zh) 2021-07-30 2024-07-19 科沃施种子欧洲股份两合公司 具有提高的消化率和标记单倍型的植物
US20240263173A1 (en) * 2021-08-11 2024-08-08 The Board Of Trustees Of The Leland Stanford Junior University High-throughput precision genome editing in human cells
CA3230927A1 (en) 2021-09-10 2023-03-16 Agilent Technologies, Inc. Guide rnas with chemical modification for prime editing
AU2022375820A1 (en) 2021-11-01 2024-06-13 Tome Biosciences, Inc. Single construct platform for simultaneous delivery of gene editing machinery and nucleic acid cargo
US20240408236A1 (en) 2021-11-26 2024-12-12 Epigenic Therapeutics, Inc. Method of modulating pcsk9 and uses thereof
WO2023114052A1 (en) 2021-12-13 2023-06-22 Labsimply, Inc. Tuning cascade assay kinetics via molecular design
WO2023114090A2 (en) 2021-12-13 2023-06-22 Labsimply, Inc. Signal boost cascade assay
AU2022420615A1 (en) 2021-12-22 2024-07-04 Tome Biosciences, Inc. Co-delivery of a gene editor construct and a donor template
WO2023205744A1 (en) 2022-04-20 2023-10-26 Tome Biosciences, Inc. Programmable gene insertion compositions
WO2023215831A1 (en) 2022-05-04 2023-11-09 Tome Biosciences, Inc. Guide rna compositions for programmable gene insertion
WO2023225670A2 (en) 2022-05-20 2023-11-23 Tome Biosciences, Inc. Ex vivo programmable gene insertion
WO2024020352A1 (en) * 2022-07-18 2024-01-25 Vertex Pharmaceuticals Incorporated Tandem guide rnas (tg-rnas) and their use in genome editing
WO2024020587A2 (en) 2022-07-22 2024-01-25 Tome Biosciences, Inc. Pleiopluripotent stem cell programmable gene insertion
CA3265393A1 (en) 2022-08-26 2024-02-29 KWS SAAT SE & Co. KGaA USE OF PAIRED GENES FOR HYBRID SELECTION
WO2024073114A1 (en) * 2022-09-30 2024-04-04 Vedabio, Inc. Delivery of therapeutics in vivo via a crispr-based cascade system
WO2024081156A1 (en) 2022-10-14 2024-04-18 Vedabio, Inc. Detection of nucleic acid and non-nucleic acid target molecules
WO2024138194A1 (en) 2022-12-22 2024-06-27 Tome Biosciences, Inc. Platforms, compositions, and methods for in vivo programmable gene insertion
WO2024253707A2 (en) 2023-01-07 2024-12-12 Vedabio, Inc. Engineered nucleic acid-guided nucleases
WO2024151493A1 (en) 2023-01-10 2024-07-18 Vedabio, Inc. Sample splitting for multiplexed detection of nucleic acids without amplification
US20240352485A1 (en) 2023-04-19 2024-10-24 Flagship Pioneering Innovations Vii, Llc Compositions and methods for the production of libraries
WO2024234006A1 (en) 2023-05-11 2024-11-14 Tome Biosciences, Inc. Systems, compositions, and methods for targeting liver sinusodial endothelial cells (lsecs)
WO2024236547A1 (en) 2023-05-18 2024-11-21 Inceptor Bio, Llc Modified phagocytic cells expressing chimeric antigen receptors comprising a herpes virus entry mediator (hvem) co-stimulatory domain and uses thereof
TW202509220A (zh) 2023-06-26 2025-03-01 美商旗艦先鋒創新有限責任(Vii)公司 經工程化之瘧原蟲及相關方法
WO2025046513A1 (en) 2023-08-29 2025-03-06 Inceptor Bio, Llc Methods of manufacturing myeloid-derived cells from hematopoietic stem cells and compositions and uses thereof
WO2025050069A1 (en) 2023-09-01 2025-03-06 Tome Biosciences, Inc. Programmable gene insertion using engineered integration enzymes
EP4677108A1 (en) 2024-04-22 2026-01-14 Basecamp Research Ltd Method and compositions for detecting off-target editing
WO2025224182A2 (en) 2024-04-23 2025-10-30 Basecamp Research Ltd Single construct platform for simultaneous delivery of gene editing machinery and nucleic acid cargo

Family Cites Families (165)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4217344A (en) 1976-06-23 1980-08-12 L'oreal Compositions containing aqueous dispersions of lipid spheres
US4235871A (en) 1978-02-24 1980-11-25 Papahadjopoulos Demetrios P Method of encapsulating biologically active materials in lipid vesicles
US4186183A (en) 1978-03-29 1980-01-29 The United States Of America As Represented By The Secretary Of The Army Liposome carriers in chemotherapy of leishmaniasis
US4261975A (en) 1979-09-19 1981-04-14 Merck & Co., Inc. Viral liposome particle
US4485054A (en) 1982-10-04 1984-11-27 Lipoderm Pharmaceuticals Limited Method of encapsulating biologically active materials in multilamellar lipid vesicles (MLV)
US4501728A (en) 1983-01-06 1985-02-26 Technology Unlimited, Inc. Masking of liposomes from RES recognition
US4897355A (en) 1985-01-07 1990-01-30 Syntex (U.S.A.) Inc. N[ω,(ω-1)-dialkyloxy]- and N-[ω,(ω-1)-dialkenyloxy]-alk-1-yl-N,N,N-tetrasubstituted ammonium lipids and uses therefor
US5049386A (en) 1985-01-07 1991-09-17 Syntex (U.S.A.) Inc. N-ω,(ω-1)-dialkyloxy)- and N-(ω,(ω-1)-dialkenyloxy)Alk-1-YL-N,N,N-tetrasubstituted ammonium lipids and uses therefor
US4946787A (en) 1985-01-07 1990-08-07 Syntex (U.S.A.) Inc. N-(ω,(ω-1)-dialkyloxy)- and N-(ω,(ω-1)-dialkenyloxy)-alk-1-yl-N,N,N-tetrasubstituted ammonium lipids and uses therefor
US4797368A (en) 1985-03-15 1989-01-10 The United States Of America As Represented By The Department Of Health And Human Services Adeno-associated virus as eukaryotic expression vector
US4774085A (en) 1985-07-09 1988-09-27 501 Board of Regents, Univ. of Texas Pharmaceutical administration systems containing a mixture of immunomodulators
DE122007000007I2 (de) 1986-04-09 2010-12-30 Genzyme Corp Genetisch transformierte Tiere, die ein gewünschtes Protein in Milch absondern
US4837028A (en) 1986-12-24 1989-06-06 Liposome Technology, Inc. Liposomes with enhanced circulation time
US4873316A (en) 1987-06-23 1989-10-10 Biogen, Inc. Isolation of exogenous recombinant proteins from the milk of transgenic mammals
US5143854A (en) 1989-06-07 1992-09-01 Affymax Technologies N.V. Large scale photolithographic solid phase synthesis of polypeptides and receptor binding screening thereof
US5264618A (en) 1990-04-19 1993-11-23 Vical, Inc. Cationic lipids for intracellular delivery of biologically active molecules
AU7979491A (en) 1990-05-03 1991-11-27 Vical, Inc. Intracellular delivery of biologically active substances by means of self-assembling lipid complexes
US5210015A (en) 1990-08-06 1993-05-11 Hoffman-La Roche Inc. Homogeneous assay system using the nuclease activity of a nucleic acid polymerase
US5173414A (en) 1990-10-30 1992-12-22 Applied Immune Sciences, Inc. Production of recombinant adeno-associated virus vectors
US7150982B2 (en) 1991-09-09 2006-12-19 Third Wave Technologies, Inc. RNA detection assays
US5587308A (en) 1992-06-02 1996-12-24 The United States Of America As Represented By The Department Of Health & Human Services Modified adeno-associated virus vector capable of expression from a novel promoter
US7745416B2 (en) 1995-04-11 2010-06-29 The Regents Of The University Of California Method for in vivo regulation of cardiac muscle contractility
EP0831854A4 (en) 1995-06-06 2001-01-24 Isis Pharmaceuticals Inc OLIGONUCLEOTIDS WITH PHOSPHOROTHIOATE BINDINGS OF HIGH CHIRAL PURITY
US5985662A (en) 1995-07-13 1999-11-16 Isis Pharmaceuticals Inc. Antisense inhibition of hepatitis B virus replication
US5622856A (en) 1995-08-03 1997-04-22 Avigen High efficiency helper system for AAV vector production
US5846946A (en) 1996-06-14 1998-12-08 Pasteur Merieux Serums Et Vaccins Compositions and methods for administering Borrelia DNA
US6251677B1 (en) 1997-08-25 2001-06-26 The Trustees Of The University Of Pennsylvania Hybrid adenovirus-AAV virus and methods of use thereof
CA2307016A1 (en) 1997-10-24 1999-05-06 Life Technologies, Inc. Recombinational cloning using nucleic acids having recombination sites
US6750059B1 (en) 1998-07-16 2004-06-15 Whatman, Inc. Archiving of vectors
US6534261B1 (en) 1999-01-12 2003-03-18 Sangamo Biosciences, Inc. Regulation of endogenous gene expression in cells using zinc finger proteins
US7868149B2 (en) 1999-07-20 2011-01-11 Monsanto Technology Llc Plant genome sequence and uses thereof
US6603061B1 (en) 1999-07-29 2003-08-05 Monsanto Company Agrobacterium-mediated plant transformation method
JP3454818B1 (ja) 2001-03-16 2003-10-06 直哉 小林 肝臓細胞の増殖方法、該方法により得られる肝臓細胞、およびその用途
ES2404689T3 (es) 2001-04-05 2013-05-28 The Johns Hopkins University Vacunas quiméricas que comprenden el dominio lumenal de LAMP-1 o LAMP-2
ES2566561T3 (es) 2001-07-12 2016-04-13 University Of Massachusetts Producción in vivo de ARN pequeños de interferencia que median el silenciamiento génico
EP1572885A2 (en) 2001-08-08 2005-09-14 Genzyme Corporation Methods for treating diabetes and other blood sugar disorders
WO2003016338A1 (en) 2001-08-15 2003-02-27 Parker Hughes Institute Crystal structure of the btk kinase domain
US7776321B2 (en) 2001-09-26 2010-08-17 Mayo Foundation For Medical Education And Research Mutable vaccines
US20090100536A1 (en) 2001-12-04 2009-04-16 Monsanto Company Transgenic plants with enhanced agronomic traits
WO2003087993A2 (en) 2002-04-09 2003-10-23 Beattie Kenneth L Oligonucleotide probes for genosensor chips
AU2003274404A1 (en) 2002-06-11 2003-12-22 The Scripps Research Institute Artificial transcription factors
AU2003283976B2 (en) 2002-09-27 2009-12-10 Cold Spring Harbor Laboratory Cell-based RNA interference and related methods and compositions
AU2003290937A1 (en) 2002-11-15 2004-06-15 Trustees Of Boston University Cis/trans riboregulators
US20060178297A1 (en) 2003-01-28 2006-08-10 Troy Carol M Systems and methods for silencing expression of a gene in a cell and uses thereof
NZ545000A (en) 2003-07-03 2008-08-29 Univ California Genome mapping of functional DNA elements and cellular proteins
EP3222715A1 (en) 2003-08-08 2017-09-27 Sangamo BioSciences, Inc. Methods and compositions for targeted cleavage and recombination
US20060171924A1 (en) * 2003-10-03 2006-08-03 Ke Luo Bidirectional promoters for small RNA expression
FR2862659B1 (fr) 2003-11-21 2006-02-10 Pasteur Institut Genome de legionella pneumophila souche paris- applications diagnostiques et epidemiologiques
WO2005070948A1 (en) 2004-01-23 2005-08-04 Intronn, Inc. Correction of alpha-1-antitrypsin genetic defects using spliceosome mediated rna trans splicing
US20070244031A1 (en) 2004-01-27 2007-10-18 Quan Lu Methods and Compositions for Homozygous Gene Inactivation Using Collections of Pre-Defined Nucleotide Sequences Complementary Chromosomal Transcripts
US20050220796A1 (en) 2004-03-31 2005-10-06 Dynan William S Compositions and methods for modulating DNA repair
FR2872170B1 (fr) 2004-06-25 2006-11-10 Centre Nat Rech Scient Cnrse Lentivirus non interactif et non replicatif, preparation et utilisations
WO2006020071A2 (en) 2004-07-16 2006-02-23 The Government Of The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services Vaccines against aids comprising cmv/r-nucleic acid constructs
AU2006239169A1 (en) 2005-04-28 2006-11-02 Benitec, Limited. Multiple-RNAi expression cassettes for simultaneous delivery of RNAi agents related to heterozygotic expression patterns
US7892224B2 (en) 2005-06-01 2011-02-22 Brainlab Ag Inverse catheter planning
CN101273141B (zh) 2005-07-26 2013-03-27 桑格摩生物科学股份有限公司 外源核酸序列的靶向整合和表达
DK2325332T3 (da) 2005-08-26 2013-01-28 Dupont Nutrition Biosci Aps Anvendelse af CRISPR-associerede gener (CAS)
EP1989307B1 (en) * 2006-02-08 2012-08-08 Quark Pharmaceuticals, Inc. NOVEL TANDEM siRNAS
WO2007106690A2 (en) 2006-03-15 2007-09-20 Siemens Healthcare Diagnostics Inc. Degenerate nucleobase analogs
ES2874149T3 (es) 2006-05-11 2021-11-04 Alnylam Pharmaceuticals Inc Composiciones y métodos para inhibir la expresión del gen PCSK9
US8748567B2 (en) 2006-05-22 2014-06-10 Children's Medical Center Corporation Method for delivery across the blood brain barrier
WO2008093152A1 (en) 2007-02-01 2008-08-07 Cellectis Obligate heterodimer meganucleases and uses thereof
AU2008223544B2 (en) 2007-03-02 2014-06-05 Dupont Nutrition Biosciences Aps Cultures with improved phage resistance
PE20090064A1 (es) 2007-03-26 2009-03-02 Novartis Ag Acido ribonucleico de doble cadena para inhibir la expresion del gen e6ap humano y composicion farmaceutica que lo comprende
JP2011512326A (ja) 2007-12-31 2011-04-21 ナノコア セラピューティクス,インコーポレイテッド 心不全の治療用のrna干渉
WO2009105690A2 (en) 2008-02-21 2009-08-27 Targeted Genetics Corporation Devices and methods for delivering polynucleotides into retinal cells of the macula and fovea
WO2010011961A2 (en) 2008-07-25 2010-01-28 University Of Georgia Research Foundation, Inc. Prokaryotic rnai-like system and methods of use
US20100076057A1 (en) 2008-09-23 2010-03-25 Northwestern University TARGET DNA INTERFERENCE WITH crRNA
WO2010054108A2 (en) 2008-11-06 2010-05-14 University Of Georgia Research Foundation, Inc. Cas6 polypeptides and methods of use
MX353900B (es) 2008-11-07 2018-02-01 Massachusetts Inst Technology Lipidoides de aminoalcohol y usos de los mismos.
US20110016540A1 (en) 2008-12-04 2011-01-20 Sigma-Aldrich Co. Genome editing of genes associated with trinucleotide repeat expansion disorders in animals
ES2627552T3 (es) 2008-12-04 2017-07-28 Sigma Aldrich Company Edición de genoma en ratas usando nucleasas con dedos de cinc
NZ593618A (en) 2008-12-10 2013-02-22 Alnylam Pharmaceuticals Inc Gnaq targeted dsrna compositions and methods for inhibiting expression
WO2010075424A2 (en) 2008-12-22 2010-07-01 The Regents Of University Of California Compositions and methods for downregulating prokaryotic genes
EP2206723A1 (en) 2009-01-12 2010-07-14 Bonas, Ulla Modular DNA-binding domains
US20110239315A1 (en) 2009-01-12 2011-09-29 Ulla Bonas Modular dna-binding domains and methods of use
WO2011036510A1 (en) 2009-09-24 2011-03-31 Cellectis Meganuclease variants cleaving the genome of the herpes simplex virus and uses thereof
US20120149115A1 (en) * 2009-06-11 2012-06-14 Snu R&Db Foundation Targeted genomic rearrangements using site-specific nucleases
KR20120097483A (ko) 2009-07-24 2012-09-04 시그마-알드리치 컴퍼니., 엘엘씨 게놈 편집을 위한 방법
JP5866283B2 (ja) 2009-07-28 2016-02-17 サンガモ バイオサイエンシーズ, インコーポレイテッド トリヌクレオチド反復疾患を治療するための方法および組成物
US8927807B2 (en) 2009-09-03 2015-01-06 The Regents Of The University Of California Nitrate-responsive promoter
US8889394B2 (en) 2009-09-07 2014-11-18 Empire Technology Development Llc Multiple domain proteins
CA2782014C (en) 2009-11-27 2021-08-31 Basf Plant Science Company Gmbh Optimized endonucleases and uses thereof
US8933046B2 (en) 2009-12-23 2015-01-13 Max-Planck-Gesellschaft Zur Foerderung Der Wissenschaften E.V. Influenza targets
AU2011215557B2 (en) 2010-02-09 2016-03-10 Sangamo Therapeutics, Inc. Targeted genomic modification with partially single-stranded donor molecules
US10087431B2 (en) 2010-03-10 2018-10-02 The Regents Of The University Of California Methods of generating nucleic acid fragments
US8927514B2 (en) 2010-04-30 2015-01-06 City Of Hope Recombinant adeno-associated vectors for targeted treatment
CA2798703A1 (en) 2010-05-10 2011-11-17 The Regents Of The University Of California Endoribonuclease compositions and methods of use thereof
KR101953237B1 (ko) 2010-05-17 2019-02-28 상가모 테라퓨틱스, 인코포레이티드 신규 dna 결합 단백질 및 이의 용도
JP2013537410A (ja) * 2010-07-23 2013-10-03 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 標的化エンドヌクレアーゼおよび一本鎖核酸を用いたゲノム編集
DK2601611T3 (da) 2010-08-02 2021-02-01 Integrated Dna Tech Inc Fremgangsmåder til forudsigelse af stabilitet og smeltetemperaturer for nukleinsyreduplekser
WO2012031205A2 (en) 2010-09-03 2012-03-08 The Brigham And Women's Hospital, Inc. Lipid-polymer hybrid particles
US9175280B2 (en) 2010-10-12 2015-11-03 Sangamo Biosciences, Inc. Methods and compositions for treating hemophilia B
US9405700B2 (en) 2010-11-04 2016-08-02 Sonics, Inc. Methods and apparatus for virtualization in an integrated circuit
HRP20220036T1 (hr) 2011-04-22 2022-04-01 The Regents Of The University Of California Virioni adeno-povezanog virusa s varijantom kapsida i postupci njihove upotrebe
SG194089A1 (en) 2011-04-27 2013-11-29 Amyris Inc Methods for genomic modification
WO2012164565A1 (en) 2011-06-01 2012-12-06 Yeda Research And Development Co. Ltd. Compositions and methods for downregulating prokaryotic genes
CA3186126A1 (en) 2011-09-21 2013-03-28 Sangamo Biosciences, Inc. Methods and compositions for regulation of transgene expression
AU2012318562A1 (en) 2011-10-06 2014-04-10 Sangamo Therapeutics, Inc. Methods and compositions for regulating HIV infection
US20130122096A1 (en) 2011-11-14 2013-05-16 Silenseed Ltd. Compositions for drug delivery and methods of manufacturing and using same
JP6259766B2 (ja) 2011-11-18 2018-01-10 ユニヴェルシテ ラヴァルUniversite Laval フラタキシンレベルを増加させる方法および生成物ならびにその使用
WO2013078400A1 (en) 2011-11-22 2013-05-30 The Children's Hospital Of Philadelphia Virus vectors for highly efficient transgene delivery
US8450107B1 (en) 2011-11-30 2013-05-28 The Broad Institute Inc. Nucleotide-specific recognition sequences for designer TAL effectors
GB201122458D0 (en) 2011-12-30 2012-02-08 Univ Wageningen Modified cascade ribonucleoproteins and uses thereof
RU2639277C2 (ru) 2012-02-29 2017-12-20 Сангамо Байосайенсиз, Инк. Способы и составы лечения болезни хантингтона
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
AU2013204327B2 (en) 2012-04-20 2016-09-01 Aviagen Cell transfection method
US10266850B2 (en) * 2012-05-25 2019-04-23 The Regents Of The University Of California Methods and compositions for RNA-directed target DNA modification and for RNA-directed modulation of transcription
CA2874828A1 (en) 2012-06-01 2013-12-05 Drexel University Modulation of hepatitis b virus cccdna transcription
JP6401704B2 (ja) 2012-10-10 2018-10-10 サンガモ セラピューティクス, インコーポレイテッド T細胞を修飾する化合物およびその使用
CN110669758A (zh) 2012-10-23 2020-01-10 基因工具股份有限公司 用于切割靶dna 的组合物及其用途
CA3034794A1 (en) 2012-12-06 2014-06-12 Sigma-Aldrich Co. Llc Crispr-based genome modification and regulation
WO2014093479A1 (en) 2012-12-11 2014-06-19 Montana State University Crispr (clustered regularly interspaced short palindromic repeats) rna-guided control of gene regulation
WO2014093701A1 (en) 2012-12-12 2014-06-19 The Broad Institute, Inc. Functional genomics using crispr-cas systems, compositions, methods, knock out libraries and applications thereof
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
EP4234696A3 (en) 2012-12-12 2023-09-06 The Broad Institute Inc. Crispr-cas component systems, methods and compositions for sequence manipulation
RU2721275C2 (ru) 2012-12-12 2020-05-18 Те Брод Инститьют, Инк. Доставка, конструирование и оптимизация систем, способов и композиций для манипуляции с последовательностями и применения в терапии
CN105121648B (zh) 2012-12-12 2021-05-07 布罗德研究所有限公司 用于序列操纵的系统、方法和优化的指导组合物的工程化
US8697359B1 (en) 2012-12-12 2014-04-15 The Broad Institute, Inc. CRISPR-Cas systems and methods for altering expression of gene products
EP2940140B1 (en) 2012-12-12 2019-03-27 The Broad Institute, Inc. Engineering of systems, methods and optimized guide compositions for sequence manipulation
EP3434776A1 (en) 2012-12-12 2019-01-30 The Broad Institute, Inc. Methods, models, systems, and apparatus for identifying target sequences for cas enzymes or crispr-cas systems for target sequences and conveying results thereof
AU2013359212B2 (en) 2012-12-12 2017-01-19 Massachusetts Institute Of Technology Engineering and optimization of improved systems, methods and enzyme compositions for sequence manipulation
WO2014093694A1 (en) 2012-12-12 2014-06-19 The Broad Institute, Inc. Crispr-cas nickase systems, methods and compositions for sequence manipulation in eukaryotes
EP2931891B1 (en) 2012-12-17 2019-05-15 President and Fellows of Harvard College Rna-guided human genome engineering
CA2898184A1 (en) 2013-01-16 2014-07-24 Emory University Cas9-nucleic acid complexes and uses related thereto
WO2014124226A1 (en) 2013-02-07 2014-08-14 The Rockefeller University Sequence specific antimicrobials
US9163837B2 (en) 2013-02-27 2015-10-20 Siemens Aktiengesellschaft Flow conditioner in a combustor of a gas turbine engine
DK3620534T3 (da) 2013-03-14 2021-12-06 Caribou Biosciences Inc Crispr-cas sammensætninger af nucleinsyre-targeting nucleinsyrer
KR102271291B1 (ko) 2013-03-15 2021-07-02 더 제너럴 하스피탈 코포레이션 특정 게놈 좌위에 대한 유전적 및 후성적 조절 단백질의 rna-안내 표적화
KR102109069B1 (ko) 2013-03-27 2020-05-12 윌코아게 디바이스들을 인라인 검사 및/또는 테스트하는 방법 및 그와 같은 방법을 수행하는 장치
JP6576904B2 (ja) 2013-04-04 2019-09-18 トラスティーズ・オブ・ダートマス・カレッジ HIV−1プロウイルスDNAのinvivo切除のための組成物及び方法
JP2016521975A (ja) 2013-05-15 2016-07-28 サンガモ バイオサイエンシーズ, インコーポレイテッド 遺伝的状態の処置のための方法および組成物
WO2014191518A1 (en) * 2013-05-29 2014-12-04 Cellectis A method for producing precise dna cleavage using cas9 nickase activity
AU2014274939B2 (en) 2013-06-04 2020-03-19 President And Fellows Of Harvard College RNA-guideded transcriptional regulation
US9267135B2 (en) 2013-06-04 2016-02-23 President And Fellows Of Harvard College RNA-guided transcriptional regulation
CN105658805B (zh) 2013-06-05 2021-12-31 杜克大学 Rna指导的基因编辑和基因调节
BR112015031608A2 (pt) 2013-06-17 2017-08-22 Massachusetts Inst Technology Aplicação e uso dos sistemas crispr-cas, vetores e composições para direcionamento e terapia hepáticos
EP3725885A1 (en) 2013-06-17 2020-10-21 The Broad Institute, Inc. Functional genomics using crispr-cas systems, compositions methods, screens and applications thereof
WO2014204729A1 (en) 2013-06-17 2014-12-24 The Broad Institute Inc. Delivery, use and therapeutic applications of the crispr-cas systems and compositions for targeting disorders and diseases using viral components
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
AU2014281030B2 (en) 2013-06-17 2020-07-09 Massachusetts Institute Of Technology Delivery, engineering and optimization of systems, methods and compositions for targeting and modeling diseases and disorders of post mitotic cells
CA2915837A1 (en) 2013-06-17 2014-12-24 The Broad Institute, Inc. Optimized crispr-cas double nickase systems, methods and compositions for sequence manipulation
SI3019619T1 (sl) 2013-07-11 2021-12-31 Modernatx, Inc. Sestave, ki zajemajo sintetične polinukleotide, ki kodirajo proteine, pozvezane s crispr, in sintetične sgrna, ter metode uporabe
CN103388006B (zh) * 2013-07-26 2015-10-28 华东师范大学 一种基因定点突变的构建方法
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
US9322037B2 (en) 2013-09-06 2016-04-26 President And Fellows Of Harvard College Cas9-FokI fusion proteins and uses thereof
US9526784B2 (en) 2013-09-06 2016-12-27 President And Fellows Of Harvard College Delivery system for functional nucleases
WO2015048577A2 (en) 2013-09-27 2015-04-02 Editas Medicine, Inc. Crispr-related methods and compositions
WO2015065964A1 (en) 2013-10-28 2015-05-07 The Broad Institute Inc. Functional genomics using crispr-cas systems, compositions, methods, screens and applications thereof
EP3066201B1 (en) 2013-11-07 2018-03-07 Editas Medicine, Inc. Crispr-related methods and compositions with governing grnas
CA2930877A1 (en) 2013-11-18 2015-05-21 Crispr Therapeutics Ag Crispr-cas system materials and methods
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
EP3080257A1 (en) 2013-12-12 2016-10-19 The Broad Institute Inc. Compositions and methods of use of crispr-cas systems in nucleotide repeat disorders
WO2015089364A1 (en) 2013-12-12 2015-06-18 The Broad Institute Inc. Crystal structure of a crispr-cas system, and uses thereof
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
CN103668472B (zh) 2013-12-31 2014-12-24 北京大学 利用CRISPR/Cas9系统构建真核基因敲除文库的方法
US10354746B2 (en) 2014-01-27 2019-07-16 Georgia Tech Research Corporation Methods and systems for identifying CRISPR/Cas off-target sites
JP6323228B2 (ja) 2014-07-18 2018-05-16 富士電機株式会社 電力変換装置
WO2016022866A1 (en) 2014-08-07 2016-02-11 Agilent Technologies, Inc. Cis-blocked guide rna
EP3180426B1 (en) 2014-08-17 2019-12-25 The Broad Institute, Inc. Genome editing using cas9 nickases
US9944912B2 (en) 2015-03-03 2018-04-17 The General Hospital Corporation Engineered CRISPR-Cas9 nucleases with altered PAM specificity
WO2016205613A1 (en) 2015-06-18 2016-12-22 The Broad Institute Inc. Crispr enzyme mutations reducing off-target effects
US9512446B1 (en) 2015-08-28 2016-12-06 The General Hospital Corporation Engineered CRISPR-Cas9 nucleases
JP6186470B2 (ja) 2016-04-20 2017-08-23 パイオニア株式会社 音響装置、音量制御方法、音量制御プログラム及び記録媒体

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US12447213B2 (en) 2016-10-07 2025-10-21 The Broad Institute, Inc. Modulation of novel immune checkpoint targets

Also Published As

Publication number Publication date
AU2014281026A9 (en) 2016-06-16
KR20160044457A (ko) 2016-04-25
US11008588B2 (en) 2021-05-18
WO2014204724A8 (en) 2015-12-23
WO2014204724A1 (en) 2014-12-24
AU2014281026A1 (en) 2016-01-28
JP2020054354A (ja) 2020-04-09
EP3674411A1 (en) 2020-07-01
CN106062197A (zh) 2016-10-26
US20160186213A1 (en) 2016-06-30
JP2016521993A (ja) 2016-07-28
HK1223646A1 (en) 2017-08-04
ES2777217T3 (es) 2020-08-04
US20210292794A1 (en) 2021-09-23
EP3011029A1 (en) 2016-04-27
WO2014204724A9 (en) 2016-03-24
AU2014281026B2 (en) 2020-05-28
EP3011029B1 (en) 2019-12-11
CA2915834A1 (en) 2014-12-24
DK3011029T3 (da) 2020-03-16

Similar Documents

Publication Publication Date Title
JP7383062B2 (ja) 配列操作のための最適化されたCRISPR-Cas二重ニッカーゼ系、方法および組成物
JP6625971B2 (ja) 配列操作のためのタンデムガイド系、方法および組成物の送達、エンジニアリングおよび最適化
JP7228059B2 (ja) 配列操作および治療適用のための系、方法および組成物の送達、エンジニアリングおよび最適化
JP6665230B2 (ja) 配列操作のための改善された系、方法および酵素組成物のエンジニアリングおよび最適化
JP6896786B2 (ja) 配列操作のためのCRISPR−Cas成分系、方法および組成物
JP2024023194A (ja) 肝臓ターゲティングおよび治療のためのCRISPR-Cas系、ベクターおよび組成物の送達および使用
JP6738729B2 (ja) 分裂終了細胞の疾患および障害をターゲティングおよびモデリングするための系、方法および組成物の送達、エンジニアリングおよび最適化
WO2014204723A9 (en) Oncogenic models based on delivery and use of the crispr-cas systems, vectors and compositions
JP2017519500A (ja) H1プロモーターを用いるcrisprガイドrnaの発現のための組成物および方法
JP2016521995A (ja) ウイルス成分を使用して障害および疾患をターゲティングするためのCRISPR−Cas系および組成物の送達、使用および治療上の適用

Legal Events

Date Code Title Description
A621 Written request for application examination

Free format text: JAPANESE INTERMEDIATE CODE: A621

Effective date: 20170608

A131 Notification of reasons for refusal

Free format text: JAPANESE INTERMEDIATE CODE: A131

Effective date: 20180828

A601 Written request for extension of time

Free format text: JAPANESE INTERMEDIATE CODE: A601

Effective date: 20181122

A601 Written request for extension of time

Free format text: JAPANESE INTERMEDIATE CODE: A601

Effective date: 20190124

A521 Request for written amendment filed

Free format text: JAPANESE INTERMEDIATE CODE: A523

Effective date: 20190228

A131 Notification of reasons for refusal

Free format text: JAPANESE INTERMEDIATE CODE: A131

Effective date: 20190528

A524 Written submission of copy of amendment under article 19 pct

Free format text: JAPANESE INTERMEDIATE CODE: A524

Effective date: 20190826

TRDD Decision of grant or rejection written
A01 Written decision to grant a patent or to grant a registration (utility model)

Free format text: JAPANESE INTERMEDIATE CODE: A01

Effective date: 20191029

A61 First payment of annual fees (during grant procedure)

Free format text: JAPANESE INTERMEDIATE CODE: A61

Effective date: 20191128

R150 Certificate of patent or registration of utility model

Ref document number: 6625971

Country of ref document: JP

Free format text: JAPANESE INTERMEDIATE CODE: R150

R250 Receipt of annual fees

Free format text: JAPANESE INTERMEDIATE CODE: R250

R250 Receipt of annual fees

Free format text: JAPANESE INTERMEDIATE CODE: R250

R250 Receipt of annual fees

Free format text: JAPANESE INTERMEDIATE CODE: R250

R250 Receipt of annual fees

Free format text: JAPANESE INTERMEDIATE CODE: R250