EA037825B1 - ВЫСОКОТОЧНЫЕ ВАРИАНТЫ Cas9 И ИХ ПРИМЕНЕНИЯ - Google Patents

ВЫСОКОТОЧНЫЕ ВАРИАНТЫ Cas9 И ИХ ПРИМЕНЕНИЯ Download PDF

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Publication number
EA037825B1
EA037825B1 EA201991913A EA201991913A EA037825B1 EA 037825 B1 EA037825 B1 EA 037825B1 EA 201991913 A EA201991913 A EA 201991913A EA 201991913 A EA201991913 A EA 201991913A EA 037825 B1 EA037825 B1 EA 037825B1
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Eurasian Patent Office
Prior art keywords
mutations
cas9
seq
target
spcas9
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EA201991913A
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English (en)
Russian (ru)
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EA201991913A1 (ru
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Анна Черезето
Антонио Казини
Джанлука Петрис
Альберто Инга
Микеле Оливьери
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Университа` Дельи Студи Ди Тренто
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Publication of EA201991913A1 publication Critical patent/EA201991913A1/ru
Publication of EA037825B1 publication Critical patent/EA037825B1/ru

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    • 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]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • C07K2319/70—Fusion polypeptide containing domain for protein-protein interaction
    • C07K2319/71—Fusion polypeptide containing domain for protein-protein interaction containing domain for transcriptional activaation, e.g. VP16
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • C07K2319/80—Fusion polypeptide containing a DNA binding domain, e.g. Lacl or Tet-repressor
    • 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
    • C12N2800/00—Nucleic acids vectors
    • C12N2800/80—Vectors containing sites for inducing double-stranded breaks, e.g. meganuclease restriction sites
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Y—ENZYMES
    • C12Y301/00—Hydrolases acting on ester bonds (3.1)

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  • Life Sciences & Earth Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Wood Science & Technology (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Zoology (AREA)
  • Genetics & Genomics (AREA)
  • Molecular Biology (AREA)
  • General Engineering & Computer Science (AREA)
  • General Health & Medical Sciences (AREA)
  • Biochemistry (AREA)
  • Medicinal Chemistry (AREA)
  • Biomedical Technology (AREA)
  • Biotechnology (AREA)
  • Microbiology (AREA)
  • Enzymes And Modification Thereof (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
  • Peptides Or Proteins (AREA)
  • Breeding Of Plants And Reproduction By Means Of Culturing (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)
  • Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)
EA201991913A 2017-02-14 2018-02-14 ВЫСОКОТОЧНЫЕ ВАРИАНТЫ Cas9 И ИХ ПРИМЕНЕНИЯ EA037825B1 (ru)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
IT102017000016321A IT201700016321A1 (it) 2017-02-14 2017-02-14 Mutanti di cas9 ad alta specificita' e loro applicazioni.
PCT/EP2018/053717 WO2018149888A1 (en) 2017-02-14 2018-02-14 High-fidelity cas9 variants and applications thereof

Publications (2)

Publication Number Publication Date
EA201991913A1 EA201991913A1 (ru) 2020-01-22
EA037825B1 true EA037825B1 (ru) 2021-05-25

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EA201991913A EA037825B1 (ru) 2017-02-14 2018-02-14 ВЫСОКОТОЧНЫЕ ВАРИАНТЫ Cas9 И ИХ ПРИМЕНЕНИЯ

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Country Link
US (1) US11525127B2 (enExample)
EP (1) EP3583209B8 (enExample)
JP (1) JP7232531B2 (enExample)
KR (1) KR20190116407A (enExample)
CN (1) CN110520528B (enExample)
AU (1) AU2018221644A1 (enExample)
BR (1) BR112019016765A2 (enExample)
CA (1) CA3053218A1 (enExample)
EA (1) EA037825B1 (enExample)
IT (1) IT201700016321A1 (enExample)
MX (1) MX2019009651A (enExample)
WO (1) WO2018149888A1 (enExample)

Families Citing this family (65)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP6261500B2 (ja) 2011-07-22 2018-01-17 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 ヌクレアーゼ切断特異性の評価および改善
US20150044192A1 (en) 2013-08-09 2015-02-12 President And Fellows Of Harvard College Methods for identifying a target site of a cas9 nuclease
US9359599B2 (en) 2013-08-22 2016-06-07 President And Fellows Of Harvard College Engineered transcription activator-like effector (TALE) domains and uses thereof
US9737604B2 (en) 2013-09-06 2017-08-22 President And Fellows Of Harvard College Use of cationic lipids to deliver CAS9
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
US9068179B1 (en) 2013-12-12 2015-06-30 President And Fellows Of Harvard College Methods for correcting presenilin point mutations
US10077453B2 (en) 2014-07-30 2018-09-18 President And Fellows Of Harvard College CAS9 proteins including ligand-dependent inteins
AU2015330699B2 (en) 2014-10-10 2021-12-02 Editas Medicine, Inc. Compositions and methods for promoting homology directed repair
AU2015342749B2 (en) 2014-11-07 2022-01-27 Editas Medicine, Inc. Methods for improving CRISPR/Cas-mediated genome-editing
CA2986310A1 (en) 2015-05-11 2016-11-17 Editas Medicine, Inc. Optimized crispr/cas9 systems and methods for gene editing in stem cells
EP3307887A1 (en) 2015-06-09 2018-04-18 Editas Medicine, Inc. Crispr/cas-related methods and compositions for improving transplantation
WO2017053879A1 (en) 2015-09-24 2017-03-30 Editas Medicine, Inc. Use of exonucleases to improve crispr/cas-mediated genome editing
EP3365356B1 (en) 2015-10-23 2023-06-28 President and Fellows of Harvard College Nucleobase editors 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
US11236313B2 (en) 2016-04-13 2022-02-01 Editas Medicine, Inc. Cas9 fusion molecules, gene editing systems, and methods of use thereof
JP7231935B2 (ja) 2016-08-03 2023-03-08 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 アデノシン核酸塩基編集因子およびそれらの使用
EP3497214B1 (en) 2016-08-09 2023-06-28 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
US11242542B2 (en) * 2016-10-07 2022-02-08 Integrated Dna Technologies, Inc. S. pyogenes Cas9 mutant genes and polypeptides encoded by same
KR102606680B1 (ko) 2016-10-07 2023-11-27 인티그레이티드 디엔에이 테크놀로지스 아이엔씨. Ｓ. 피오게네스 ｃａｓ９ 돌연변이 유전자 및 이에 의해 암호화되는 폴리펩티드
EP3526320A1 (en) 2016-10-14 2019-08-21 President and Fellows of Harvard College Aav delivery of nucleobase editors
US11377645B2 (en) 2016-12-16 2022-07-05 The Rockefeller University Compositions and methods using Cas9 with enhanced spacer acquisition function
WO2018119010A1 (en) 2016-12-19 2018-06-28 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
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
IT201700016321A1 (it) 2017-02-14 2018-08-14 Univ Degli Studi Di Trento Mutanti di cas9 ad alta specificita' e loro applicazioni.
WO2018165631A1 (en) 2017-03-09 2018-09-13 President And Fellows Of Harvard College Cancer vaccine
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
KR20240116572A (ko) 2017-03-23 2024-07-29 프레지던트 앤드 펠로우즈 오브 하바드 칼리지 핵산 프로그램가능한 dna 결합 단백질을 포함하는 핵염기 편집제
WO2018201086A1 (en) 2017-04-28 2018-11-01 Editas Medicine, Inc. Methods and systems for analyzing guide rna molecules
US11560566B2 (en) 2017-05-12 2023-01-24 President And Fellows Of Harvard College Aptazyme-embedded guide RNAs for use with CRISPR-Cas9 in genome editing and transcriptional activation
MX2019014640A (es) 2017-06-09 2020-10-05 Editas Medicine Inc Nucleasas de repeticiones palíndromicas agrupadas y regularmente interespaciadas de proteina asociada 9 (cas9) genomanipuladas.
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
WO2019023680A1 (en) 2017-07-28 2019-01-31 President And Fellows Of Harvard College METHODS AND COMPOSITIONS FOR EVOLUTION OF BASIC EDITORS USING PHAGE-ASSISTED CONTINUOUS EVOLUTION (PACE)
EP3676376B1 (en) 2017-08-30 2025-01-15 President and Fellows of Harvard College High efficiency base editors comprising gam
CN111757937A (zh) 2017-10-16 2020-10-09 布罗德研究所股份有限公司 腺苷碱基编辑器的用途
WO2019118949A1 (en) 2017-12-15 2019-06-20 The Broad Institute, Inc. Systems and methods for predicting repair outcomes in genetic engineering
US12157760B2 (en) 2018-05-23 2024-12-03 The Broad Institute, Inc. Base editors and uses thereof
CA3104856A1 (en) 2018-06-29 2020-01-02 Editas Medicine, Inc. Synthetic guide molecules, compositions and methods relating thereto
KR20210060541A (ko) * 2018-09-19 2021-05-26 더 유니버시티 오브 홍콩 개선된 고처리량 조합 유전적 변형 시스템 및 최적화된 Cas9 효소 변이체
US12281338B2 (en) 2018-10-29 2025-04-22 The Broad Institute, Inc. Nucleobase editors comprising GeoCas9 and uses thereof
WO2020154500A1 (en) 2019-01-23 2020-07-30 The Broad Institute, Inc. Supernegatively charged proteins and uses thereof
WO2020160125A1 (en) * 2019-01-29 2020-08-06 Flagship Pioneering Innovations V, Inc. Compositions comprising an endonuclease and methods for purifying an endonuclease
MX2021011426A (es) 2019-03-19 2022-03-11 Broad Inst Inc Metodos y composiciones para editar secuencias de nucleótidos.
EP3956349A1 (en) 2019-04-17 2022-02-23 The Broad Institute, Inc. Adenine base editors with reduced off-target effects
WO2020257325A1 (en) * 2019-06-17 2020-12-24 Vertex Pharmaceuticals Inc. Compositions and methods for editing beta-globin for treatment of hemaglobinopathies
US12435330B2 (en) 2019-10-10 2025-10-07 The Broad Institute, Inc. Methods and compositions for prime editing RNA
JP7680440B2 (ja) * 2019-10-15 2025-05-20 エージェンシー フォー サイエンス， テクノロジー アンド リサーチ 核酸修飾酵素活性を測定するためのアッセイ法
WO2021122944A1 (en) 2019-12-18 2021-06-24 Alia Therapeutics Srl Compositions and methods for treating retinitis pigmentosa
AU2021236230B2 (en) * 2020-03-11 2024-09-26 Sigma-Aldrich Co. Llc High fidelity SpCas9 nucleases for genome modification
MX2022014008A (es) 2020-05-08 2023-02-09 Broad Inst Inc Métodos y composiciones para la edición simultánea de ambas cadenas de una secuencia de nucleótidos de doble cadena objetivo.
WO2022018638A1 (en) 2020-07-21 2022-01-27 Crispr Therapeutics Ag Genome-editing compositions and methods to modulate faah for treatment of neurological disorders
CA3205138A1 (en) 2020-12-17 2022-06-23 Vertex Pharmaceuticals Incorporated Compositions and methods for editing beta-globin for treatment of hemaglobinopathies
CN112680430B (zh) * 2020-12-28 2023-06-06 南方医科大学 一种CRISPR SpCas9突变体及其应用
CN113005141A (zh) * 2021-01-05 2021-06-22 温州医科大学 高活性突变体构成的基因编辑工具及制备方法和修复先天性视网膜劈裂症致病基因的方法
WO2022152746A1 (en) 2021-01-13 2022-07-21 Alia Therapeutics Srl K526d cas9 variants and applications thereof
CN112626070A (zh) * 2021-01-13 2021-04-09 海南微氪生物科技股份有限公司 一种基于切离酶基因编辑技术的定向修复系统
WO2022238958A1 (en) 2021-05-12 2022-11-17 Crispr Therapeutics Ag Multiplex gene editing
WO2023285431A1 (en) 2021-07-12 2023-01-19 Alia Therapeutics Srl Compositions and methods for allele specific treatment of retinitis pigmentosa
US20240382528A1 (en) * 2021-10-05 2024-11-21 The Board Of Trustees Of The Leland Stanford Junior University Treatment of polycythemia vera via crispr/aav6 genome editing
WO2025087413A1 (zh) * 2023-10-25 2025-05-01 上海津曼特生物科技有限公司 靶向ttr的基因编辑组合物
CN117887760A (zh) * 2024-01-22 2024-04-16 中国医学科学院北京协和医院 SQSTM1/p62基因新致病突变c.1143delC的敲入小鼠模型及其构建方法
CN118497204B (zh) * 2024-07-16 2024-12-03 西北农林科技大学深圳研究院 一种质粒CRISPR-pCas9n及基因编辑的方法与应用

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2016164797A1 (en) * 2015-04-08 2016-10-13 University Of Pittsburgh - Of The Commonwealth System Of Higher Education Activatable crispr/cas9 for spatial and temporal control of genome editing
US9512446B1 (en) * 2015-08-28 2016-12-06 The General Hospital Corporation Engineered CRISPR-Cas9 nucleases
WO2016205613A1 (en) * 2015-06-18 2016-12-22 The Broad Institute Inc. Crispr enzyme mutations reducing off-target effects

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US11685935B2 (en) * 2013-05-29 2023-06-27 Cellectis Compact scaffold of Cas9 in the type II CRISPR system
US11180792B2 (en) * 2015-01-28 2021-11-23 The Regents Of The University Of California Methods and compositions for labeling a single-stranded target nucleic acid
US9944912B2 (en) 2015-03-03 2018-04-17 The General Hospital Corporation Engineered CRISPR-Cas9 nucleases with altered PAM specificity
IT201700016321A1 (it) 2017-02-14 2018-08-14 Univ Degli Studi Di Trento Mutanti di cas9 ad alta specificita' e loro applicazioni.

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2016164797A1 (en) * 2015-04-08 2016-10-13 University Of Pittsburgh - Of The Commonwealth System Of Higher Education Activatable crispr/cas9 for spatial and temporal control of genome editing
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

Non-Patent Citations (4)

* Cited by examiner, † Cited by third party
Title
BENJAMIN P. KLEINSTIVER, PATTANAYAK VIKRAM, PREW MICHELLE S., TSAI SHENGDAR Q., NGUYEN NHU T., ZHENG ZONGLI, JOUNG J. KEITH: "High-fidelity CRISPR–Cas9 nucleases with no detectable genome-wide off-target effects", NATURE, MACMILLAN JOURNALS LTD., ETC, LONDON, vol. 529, no. 7587, 28 January 2016 (2016-01-28), London, pages 490 - 495, XP055303390, ISSN: 0028-0836, DOI: 10.1038/nature16526 *
CASINI A. ET AL.: "Identification of high-fidelity Cas9 variants using a yeast-based screening", HUMAN GENE THERAPY, vol. 27, no. 11, 18 October 2016 (2016-10-18), 21 October 2016 (2016-10-21), page A41, & CONFERENCE ON CHANGING THE FACE OF MODERN MEDICINE - STEM CELLS AND GENE THERAPY; FLORENCE, ITALY, the whole document *
IAN M. SLAYMAKER, LINYI GAO, BERND ZETSCHE, DAVID A. SCOTT, WINSTON X. YAN, FENG ZHANG: "Rationally engineered Cas9 nucleases with improved specificity", SCIENCE, AMERICAN ASSOCIATION FOR THE ADVANCEMENT OF SCIENCE, US, vol. 351, no. 6268, 1 January 2016 (2016-01-01), US, pages 84 - 88, XP002757561, ISSN: 0036-8075, DOI: 10.1126/science.aad5227 *
M. JINEK, F. JIANG, D. W. TAYLOR, S. H. STERNBERG, E. KAYA, E. MA, C. ANDERS, M. HAUER, K. ZHOU, S. LIN, M. KAPLAN, A. T. IAVARONE: "Structures of Cas9 Endonucleases Reveal RNA-Mediated Conformational Activation", SCIENCE, AMERICAN ASSOCIATION FOR THE ADVANCEMENT OF SCIENCE, vol. 343, no. 6176, 14 March 2014 (2014-03-14), pages 1247997 - 1247997, XP055149157, ISSN: 00368075, DOI: 10.1126/science.1247997 *

Also Published As

Publication number Publication date
CA3053218A1 (en) 2018-08-23
JP7232531B2 (ja) 2023-03-03
AU2018221644A1 (en) 2019-08-29
MX2019009651A (es) 2019-12-18
JP2020507347A (ja) 2020-03-12
WO2018149888A1 (en) 2018-08-23
BR112019016765A2 (pt) 2020-05-26
IT201700016321A1 (it) 2018-08-14
EA201991913A1 (ru) 2020-01-22
EP3583209A1 (en) 2019-12-25
CN110520528B (zh) 2024-08-13
KR20190116407A (ko) 2019-10-14
US11525127B2 (en) 2022-12-13
EP3583209C0 (en) 2024-12-04
CN110520528A (zh) 2019-11-29
EP3583209B1 (en) 2024-12-04
US20200149020A1 (en) 2020-05-14
EP3583209B8 (en) 2025-02-26

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