RU2014127702A - Модифицированные Cascade-рибонуклеопротеины и их применения - Google Patents

Модифицированные Cascade-рибонуклеопротеины и их применения Download PDF

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RU2014127702A
RU2014127702A RU2014127702A RU2014127702A RU2014127702A RU 2014127702 A RU2014127702 A RU 2014127702A RU 2014127702 A RU2014127702 A RU 2014127702A RU 2014127702 A RU2014127702 A RU 2014127702A RU 2014127702 A RU2014127702 A RU 2014127702A
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Стан Йохан Йозеф БРАУНС
ДЕР ОСТ Джон ВАН
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Вагенинген Юниверситейт
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Abstract

1. Способ модификации целевой нуклеиновой кислоты in situ в эукариотической клетке, включающий:(а) приведение указанной целевой нуклеиновой кислоты в контакт с рибонуклеопротеином, содержащим CRISPR РНК (производное РНК и кластерных коротких палиндромных повторов, разделенных регулярными промежутками); и(б) модификацию указанной целевой нуклеиновой кислоты в указанной эукариотической клетке.2. Способ по п. 1, где указанная целевая нуклеиновая кислота содержит мотив, примыкающий к протоспейсеру, расположенный рядом с последовательностью, с которой гибридизуется CRISP РНК.3. Способ по п. 2, где указанный мотив, примыкающий к протоспейсеру, маркирует точку в указанной целевой нуклеиновой кислоте, в которой происходит спаривание оснований с указанной CRISPR РНК.4. Способ по п. 2, где указанный мотив, примыкающий к протоспейсеру, содержит 5′-ССТ-3′.5. Способ по п. 2, где указанный мотив, примыкающий к протоспейсеру, содержит 5′-СТТ-3′.6. Способ по п. 2, где указанный мотив, примыкающий к протоспейсеру, содержит 5′-САТ-3′.7. Способ по п. 2, где указанный мотив, примыкающий к протоспейсеру, содержит 5′-СТС-3′.8. Способ по п. 2, где указанный мотив, примыкающий к протоспейсеру, представляет собой 5′-ССТ-3′.9. Способ по п. 1, где указанную CRISPR РНК получают путем экспрессии в генетически модифицированных клетках.10. Способ по п. 1, где указанная целевая нуклеиновая кислота представляет собой двухцепочечную нуклеиновую кислоту.11. Способ по п. 1, где указанная целевая нуклеиновая кислота представляет собой одноцепочечную ДНК.12. Способ по п. 1, где указанная целевая нуклеиновая кислота представляет собой двухцепочечную ДНК.13. Способ по п. 1, где указанная целевая нуклеиновая кислота представляет собой геномную ДНК.14. Способ по п. 1, г

Claims (27)

1. Способ модификации целевой нуклеиновой кислоты in situ в эукариотической клетке, включающий:
(а) приведение указанной целевой нуклеиновой кислоты в контакт с рибонуклеопротеином, содержащим CRISPR РНК (производное РНК и кластерных коротких палиндромных повторов, разделенных регулярными промежутками); и
(б) модификацию указанной целевой нуклеиновой кислоты в указанной эукариотической клетке.
2. Способ по п. 1, где указанная целевая нуклеиновая кислота содержит мотив, примыкающий к протоспейсеру, расположенный рядом с последовательностью, с которой гибридизуется CRISP РНК.
3. Способ по п. 2, где указанный мотив, примыкающий к протоспейсеру, маркирует точку в указанной целевой нуклеиновой кислоте, в которой происходит спаривание оснований с указанной CRISPR РНК.
4. Способ по п. 2, где указанный мотив, примыкающий к протоспейсеру, содержит 5′-ССТ-3′.
5. Способ по п. 2, где указанный мотив, примыкающий к протоспейсеру, содержит 5′-СТТ-3′.
6. Способ по п. 2, где указанный мотив, примыкающий к протоспейсеру, содержит 5′-САТ-3′.
7. Способ по п. 2, где указанный мотив, примыкающий к протоспейсеру, содержит 5′-СТС-3′.
8. Способ по п. 2, где указанный мотив, примыкающий к протоспейсеру, представляет собой 5′-ССТ-3′.
9. Способ по п. 1, где указанную CRISPR РНК получают путем экспрессии в генетически модифицированных клетках.
10. Способ по п. 1, где указанная целевая нуклеиновая кислота представляет собой двухцепочечную нуклеиновую кислоту.
11. Способ по п. 1, где указанная целевая нуклеиновая кислота представляет собой одноцепочечную ДНК.
12. Способ по п. 1, где указанная целевая нуклеиновая кислота представляет собой двухцепочечную ДНК.
13. Способ по п. 1, где указанная целевая нуклеиновая кислота представляет собой геномную ДНК.
14. Способ по п. 1, где спейсерный участок CRISPR РНК имеет по меньшей мере 50%-ную идентичность с целевой нуклеиновокислотной последовательностью.
15. Способ по п. 14, где спейсерный участок CRISPR РНК имеет 32 нуклеотида.
16. Способ по п. 1, где указанная модификация включает расщепление указанной целевой нуклеиновой кислоты.
17. Способ по п. 1, где указанная модификация включает негомологичное соединения концов молекулы дцДНК в клетке в нужном локусе для удаления по меньшей мере части нуклеотидной последовательности из этой молекулы ДЦДНК.
18. Способ по п. 1, где указанная модификация включает гомологичную рекомбинацию нуклеиновой кислоты в молекулу дцДНК в клетке в нужном локусе.
19. Способ по п. 1, где указанная клетка представляет собой клетку насекомого.
20. Способ по п. 1, где указанная клетка представляет собой клетку млекопитающего.
21. Способ по п. 20, где указанная клетка представляет собой стволовую клетку млекопитающего, не являющуюся стволовой клеткой человеческого эмбриона.
22. Способ по п. 20, где указанная клетка представляет собой клетку человека.
23. Способ по п. 22, где указанная клетка представляет собой стволовую клетку человека, не являющуюся стволовой клеткой человеческого эмбриона.
24. Способ по п. 1, где указанная клетка представляет собой клетку растения.
25. Способ по п. 1, где указанная клетка представляет собой дрожжевую клетку.
26. Способ по п. 1, где указанная клетка представляет собой клетку гриба.
27. Способ изменения экспрессии целевой нуклеиновой кислоты, включающий введение в эукариотическую клетку, содержащую молекулу ДНК, кодирующую указанную целевую нуклеиновую кислоту, сконструированной системы кластерных коротких палиндромных повторов, разделенных регулярными промежутками, содержащей один или более векторов, содержащих: (а) первую нуклеотидную последовательность, кодирующую РНК со сконструированными кластерными короткими палиндромными повторами, разделенными регулярными промежутками, которая гибридизуется с целевой нуклеиновой кислотой, и б) вторую нуклеотидную последовательность, кодирующую пептид, ассоциированный с кластерными короткими палиндромными повторами, разделенными регулярными промежутками, где компоненты (а) и (б) находятся в одном векторе или в разных векторах этой системы, посредством чего указанная РНК нацеливается на указанную нуклеиновую кислоту, и указанный пептид, ассоциированный с кластерными короткими палиндромными повторами, разделенными регулярными промежутками, расщепляет указанную молекулу ДНК.
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Families Citing this family (206)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7790756B2 (en) 2006-10-11 2010-09-07 Deciphera Pharmaceuticals, Llc Kinase inhibitors useful for the treatment of myleoproliferative diseases and other proliferative diseases
SG185481A1 (en) 2010-05-10 2012-12-28 Univ California Endoribonuclease compositions and methods of use thereof
WO2013066438A2 (en) 2011-07-22 2013-05-10 President And Fellows Of Harvard College Evaluation and improvement of nuclease cleavage specificity
IN2014MN00974A (ru) 2011-12-16 2015-04-24 Targetgene Biotechnologies Ltd
US11021737B2 (en) 2011-12-22 2021-06-01 President And Fellows Of Harvard College Compositions and methods for analyte detection
GB201122458D0 (en) 2011-12-30 2012-02-08 Univ Wageningen Modified cascade ribonucleoproteins and uses thereof
EP2841572B1 (en) 2012-04-27 2019-06-19 Duke University Genetic correction of mutated genes
LT3401400T (lt) 2012-05-25 2019-06-10 The Regents Of The University Of California Būdai ir kompozicijos, skirtos rnr molekulės nukreipiamai tikslinės dnr modifikacijai ir rnr molekulės nukreipiamam transkripcijos moduliavimui
DE202013012597U1 (de) 2012-10-23 2017-11-21 Toolgen, Inc. Zusammensetzung zum Spalten einer Ziel-DNA, umfassend eine für die Ziel-DNA spezifische guide-RNA und eine Cas-Protein-codierende Nukleinsäure oder ein Cas-Protein, sowie deren Verwendung
EP3138911B1 (en) 2012-12-06 2018-12-05 Sigma Aldrich Co. LLC Crispr-based genome modification and regulation
US8697359B1 (en) 2012-12-12 2014-04-15 The Broad Institute, Inc. CRISPR-Cas systems and methods for altering expression of gene products
PT2921557T (pt) 2012-12-12 2016-10-19 Massachusetts Inst Technology Engenharia de sistemas, métodos e composições guia otimizadas para a manipulação de sequências
ES2576128T3 (es) 2012-12-12 2016-07-05 The Broad Institute, Inc. Modificación por tecnología genética y optimización de sistemas, métodos y composiciones para la manipulación de secuencias con dominios funcionales
WO2014093694A1 (en) 2012-12-12 2014-06-19 The Broad Institute, Inc. Crispr-cas nickase systems, methods and compositions for sequence manipulation in eukaryotes
DK2898075T3 (en) 2012-12-12 2016-06-27 Broad Inst Inc CONSTRUCTION AND OPTIMIZATION OF IMPROVED SYSTEMS, PROCEDURES AND ENZYME COMPOSITIONS FOR SEQUENCE MANIPULATION
ES2658401T3 (es) 2012-12-12 2018-03-09 The Broad Institute, Inc. Suministro, modificación y optimización de sistemas, métodos y composiciones para la manipulación de secuencias y aplicaciones terapéuticas
EP4234696A3 (en) 2012-12-12 2023-09-06 The Broad Institute Inc. Crispr-cas component systems, methods and compositions for sequence manipulation
EP2931892B1 (en) 2012-12-12 2018-09-12 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
CA3081054A1 (en) 2012-12-17 2014-06-26 President And Fellows Of Harvard College Rna-guided human genome engineering
US10138509B2 (en) 2013-03-12 2018-11-27 President And Fellows Of Harvard College Method for generating a three-dimensional nucleic acid containing matrix
KR101780885B1 (ko) 2013-03-14 2017-10-11 카리부 바이오사이언시스 인코포레이티드 핵산-표적화 핵산의 조성물 및 방법
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
CA2906553C (en) 2013-03-15 2022-08-02 The General Hospital Corporation Rna-guided targeting of genetic and epigenomic regulatory proteins to specific genomic loci
US9902973B2 (en) 2013-04-11 2018-02-27 Caribou Biosciences, Inc. Methods of modifying a target nucleic acid with an argonaute
US20140356956A1 (en) 2013-06-04 2014-12-04 President And Fellows Of Harvard College RNA-Guided Transcriptional Regulation
KR20160030187A (ko) 2013-06-17 2016-03-16 더 브로드 인스티튜트, 인코퍼레이티드 간의 표적화 및 치료를 위한 ＣＲＩＳＰＲ­Ｃａｓ 시스템, 벡터 및 조성물의 전달 및 용도
WO2014204725A1 (en) 2013-06-17 2014-12-24 The Broad Institute Inc. Optimized crispr-cas double nickase systems, methods and compositions for sequence manipulation
WO2014204727A1 (en) 2013-06-17 2014-12-24 The Broad Institute Inc. Functional genomics using crispr-cas systems, compositions methods, screens and applications thereof
ES2777217T3 (es) 2013-06-17 2020-08-04 Broad Inst Inc Suministro, modificación y optimización de sistemas de guía en tándem, métodos y composiciones para la manipulación de secuencias
EP3011034B1 (en) 2013-06-17 2019-08-07 The Broad Institute, Inc. Delivery, use and therapeutic applications of the crispr-cas systems and compositions for targeting disorders and diseases using viral components
US10011850B2 (en) 2013-06-21 2018-07-03 The General Hospital Corporation Using RNA-guided FokI Nucleases (RFNs) to increase specificity for RNA-Guided Genome Editing
CN105517579B (zh) 2013-07-10 2019-11-15 哈佛大学校长及研究员协会 用于RNA向导的基因调节和编辑的正交Cas9蛋白
US11060083B2 (en) 2013-07-19 2021-07-13 Larix Bioscience Llc Methods and compositions for producing double allele knock outs
CN105392885B (zh) * 2013-07-19 2020-11-03 赖瑞克斯生物科技公司 用于产生双等位基因敲除的方法和组合物
US11306328B2 (en) * 2013-07-26 2022-04-19 President And Fellows Of Harvard College Genome engineering
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
US9163284B2 (en) 2013-08-09 2015-10-20 President And Fellows Of Harvard College Methods for identifying a target site of a Cas9 nuclease
WO2015021426A1 (en) * 2013-08-09 2015-02-12 Sage Labs, Inc. A crispr/cas system-based novel fusion protein and its application in genome editing
US9359599B2 (en) 2013-08-22 2016-06-07 President And Fellows Of Harvard College Engineered transcription activator-like effector (TALE) domains and uses thereof
CA3109801C (en) 2013-08-22 2024-01-09 Andrew Cigan Plant genome modification using guide rna/cas endonuclease systems and methods of use
EA037850B1 (ru) 2013-08-29 2021-05-27 Тэмпл Юниверсити Оф Зе Коммонвэлс Систем Оф Хайе Эдьюкейшн Способы и композиции для рнк-направленного лечения вич-инфекции
US9228207B2 (en) 2013-09-06 2016-01-05 President And Fellows Of Harvard College Switchable gRNAs comprising aptamers
US9526784B2 (en) 2013-09-06 2016-12-27 President And Fellows Of Harvard College Delivery system for functional nucleases
US9322037B2 (en) 2013-09-06 2016-04-26 President And Fellows Of Harvard College Cas9-FokI fusion proteins and uses thereof
ES2844174T3 (es) 2013-09-18 2021-07-21 Kymab Ltd Métodos, células y organismos
WO2015065964A1 (en) 2013-10-28 2015-05-07 The Broad Institute Inc. Functional genomics using crispr-cas systems, compositions, methods, screens and applications thereof
US10584358B2 (en) 2013-10-30 2020-03-10 North Carolina State University Compositions and methods related to a type-II CRISPR-Cas system in Lactobacillus buchneri
LT3066201T (lt) 2013-11-07 2018-08-10 Editas Medicine, Inc. Su crispr susiję būdai ir kompozicijos su valdančiomis grnr
US9074199B1 (en) 2013-11-19 2015-07-07 President And Fellows Of Harvard College Mutant Cas9 proteins
US10787684B2 (en) 2013-11-19 2020-09-29 President And Fellows Of Harvard College Large gene excision and insertion
US20150165054A1 (en) 2013-12-12 2015-06-18 President And Fellows Of Harvard College Methods for correcting caspase-9 point mutations
KR20160089527A (ko) 2013-12-12 2016-07-27 더 브로드 인스티튜트, 인코퍼레이티드 게놈 편집을 위한 ｃｒｉｓｐｒ-ｃａｓ 시스템 및 조성물의 전달, 용도 및 치료적 응용
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
WO2015089364A1 (en) 2013-12-12 2015-06-18 The Broad Institute Inc. Crystal structure of a crispr-cas system, and uses thereof
KR20160097327A (ko) 2013-12-12 2016-08-17 더 브로드 인스티튜트, 인코퍼레이티드 유전자 산물, 구조 정보 및 유도성 모듈형 ｃａｓ 효소의 발현의 변경을 위한 ｃｒｉｓｐｒ-ｃａｓ 시스템 및 방법
WO2015089354A1 (en) 2013-12-12 2015-06-18 The Broad Institute Inc. Compositions and methods of use of crispr-cas systems in nucleotide repeat disorders
JP6652489B2 (ja) 2013-12-19 2020-02-26 アミリス， インコーポレイテッド ゲノム組込みのための方法
US10787654B2 (en) 2014-01-24 2020-09-29 North Carolina State University Methods and compositions for sequence guiding Cas9 targeting
WO2015133554A1 (ja) 2014-03-05 2015-09-11 国立大学法人神戸大学 標的化したｄｎａ配列の核酸塩基を特異的に変換するゲノム配列の改変方法及びそれに用いる分子複合体
EP3957735A1 (en) 2014-03-05 2022-02-23 Editas Medicine, Inc. Crispr/cas-related methods and compositions for treating usher syndrome and retinitis pigmentosa
EP3553176A1 (en) 2014-03-10 2019-10-16 Editas Medicine, Inc. Crispr/cas-related methods and compositions for treating leber's congenital amaurosis 10 (lca10)
US11339437B2 (en) 2014-03-10 2022-05-24 Editas Medicine, Inc. Compositions and methods for treating CEP290-associated disease
US11141493B2 (en) 2014-03-10 2021-10-12 Editas Medicine, Inc. Compositions and methods for treating CEP290-associated disease
EP3122880B1 (en) 2014-03-26 2021-05-05 Editas Medicine, Inc. Crispr/cas-related methods and compositions for treating sickle cell disease
AU2015237746B2 (en) * 2014-03-28 2020-01-30 Aposense Ltd. Compounds and methods for trans-membrane delivery of molecules
US11318206B2 (en) 2014-03-28 2022-05-03 Aposense Ltd Compounds and methods for trans-membrane delivery of molecules
WO2015155686A2 (en) * 2014-04-08 2015-10-15 North Carolina State University Methods and compositions for rna-directed repression of transcription using crispr-associated genes
IL286474B2 (en) 2014-06-23 2023-11-01 Massachusetts Gen Hospital Genome-wide random identification of DSBS assessed by sequencing (guide-sequence)
AU2015288157A1 (en) 2014-07-11 2017-01-19 E. I. Du Pont De Nemours And Company Compositions and methods for producing plants resistant to glyphosate herbicide
US10077453B2 (en) 2014-07-30 2018-09-18 President And Fellows Of Harvard College CAS9 proteins including ligand-dependent inteins
AU2015308910B2 (en) 2014-08-27 2017-12-07 Caribou Biosciences, Inc. Methods for increasing Cas9-mediated engineering efficiency
EP3186375A4 (en) 2014-08-28 2019-03-13 North Carolina State University NEW CAS9 PROTEINS AND GUIDING ELEMENTS FOR DNA TARGETING AND THE GENOME EDITION
CN108064129A (zh) 2014-09-12 2018-05-22 纳幕尔杜邦公司 玉米和大豆中复合性状基因座的位点特异性整合位点的产生和使用方法
CA2963820A1 (en) 2014-11-07 2016-05-12 Editas Medicine, Inc. Methods for improving crispr/cas-mediated genome-editing
KR20240013283A (ko) 2014-12-03 2024-01-30 애질런트 테크놀로지스, 인크. 화학적 변형을 갖는 가이드 rna
KR102656470B1 (ko) 2014-12-10 2024-04-09 리전츠 오브 더 유니버스티 오브 미네소타 질환을 치료하기 위한 유전적으로 변형된 세포, 조직 및 장기
EP3985115A1 (en) 2014-12-12 2022-04-20 The Broad Institute, Inc. Protected guide rnas (pgrnas)
KR102319192B1 (ko) 2015-01-28 2021-10-28 카리부 바이오사이언시스 인코포레이티드 Crispr 하이브리드 dna/rna 폴리뉴클레오티드 및 사용 방법
EP3265559B1 (en) 2015-03-03 2021-01-06 The General Hospital Corporation Engineered crispr-cas9 nucleases with altered pam specificity
WO2016153305A1 (ko) * 2015-03-26 2016-09-29 한국생명공학연구원 표적 유전자 특이적 핵산 프로브 및 Fok Ι 제한효소 이량체를 이용하여 세포 내에서 표적 유전자를 특이적으로 편집하기 위한 조성물 및 이의 용도
CN107567499A (zh) 2015-03-27 2018-01-09 纳幕尔杜邦公司 大豆u6核小rna基因启动子及其在植物小rna基因的组成型表达中的用途
JP6873911B2 (ja) 2015-04-06 2021-05-19 ザ ボード オブ トラスティーズ オブ ザ レランド スタンフォード ジュニア ユニバーシティー 初代細胞において標的核酸の遺伝子調節を誘導するためにインビトロで行う方法
JP2018522249A (ja) 2015-04-24 2018-08-09 エディタス・メディシン、インコーポレイテッド Ｃａｓ９分子／ガイドｒｎａ分子複合体の評価
JP7030522B2 (ja) 2015-05-11 2022-03-07 エディタス・メディシン、インコーポレイテッド 幹細胞における遺伝子編集のための最適化ｃｒｉｓｐｒ／ｃａｓ９システムおよび方法
KR102451796B1 (ko) 2015-05-29 2022-10-06 노쓰 캐롤라이나 스테이트 유니버시티 크리스퍼 핵산을 사용하여 박테리아, 고세균, 조류 및 효모를 스크리닝하는 방법
EP3302053B1 (en) 2015-06-02 2021-03-17 Monsanto Technology LLC Compositions and methods for delivery of a polynucleotide into a plant
CN108368502B (zh) 2015-06-03 2022-03-18 内布拉斯加大学董事委员会 使用单链dna的dna编辑
WO2016201047A1 (en) 2015-06-09 2016-12-15 Editas Medicine, Inc. Crispr/cas-related methods and compositions for improving transplantation
KR20220158846A (ko) 2015-06-15 2022-12-01 노쓰 캐롤라이나 스테이트 유니버시티 핵산 및 rna-기반 항미생물제를 효율적으로 전달하기 위한 방법 및 조성물
AU2016280893B2 (en) 2015-06-18 2021-12-02 Massachusetts Institute Of Technology CRISPR enzyme mutations reducing off-target effects
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
EP3325668B1 (en) * 2015-07-23 2021-01-06 Mayo Foundation for Medical Education and Research Editing mitochondrial dna
IL295616A (en) 2015-07-31 2022-10-01 Us Health Adapted cells and treatment methods
US9580727B1 (en) 2015-08-07 2017-02-28 Caribou Biosciences, Inc. Compositions and methods of engineered CRISPR-Cas9 systems using split-nexus Cas9-associated polynucleotides
JP6799586B2 (ja) 2015-08-28 2020-12-16 ザ ジェネラル ホスピタル コーポレイション 遺伝子操作ＣＲＩＳＰＲ−Ｃａｓ９ヌクレアーゼ
US9512446B1 (en) 2015-08-28 2016-12-06 The General Hospital Corporation Engineered CRISPR-Cas9 nucleases
US9926546B2 (en) 2015-08-28 2018-03-27 The General Hospital Corporation Engineered CRISPR-Cas9 nucleases
ES2902338T3 (es) * 2015-09-09 2022-03-28 Univ Kobe Nat Univ Corp Método para modificar una secuencia genómica que convierte específicamente una nucleobase de una secuencia de ADN diana, y complejo molecular utilizado en dicho método
DK3348638T3 (da) 2015-09-09 2023-02-13 Univ Kobe Nat Univ Corp Fremgangsmåde til at konvertere genomsekvens fra gram-positiv bakterie ved specifikt at konvertere nukleinsyrebase i tilsigtet dna-sekvens, og molekylkompleks anvendt dertil
JP2018530536A (ja) 2015-09-11 2018-10-18 ザ ジェネラル ホスピタル コーポレイション ヌクレアーゼＤＳＢの完全照合およびシーケンシング（ＦＩＮＤ−ｓｅｑ）
EP3786294A1 (en) 2015-09-24 2021-03-03 Editas Medicine, Inc. Use of exonucleases to improve crispr/cas-mediated genome editing
US11286480B2 (en) 2015-09-28 2022-03-29 North Carolina State University Methods and compositions for sequence specific antimicrobials
JP2018529353A (ja) 2015-09-30 2018-10-11 ザ ジェネラル ホスピタル コーポレイション 配列決定法による切断事象の包括的生体外報告（ＣＩＲＣＬＥ−ｓｅｑ）
CN105331627B (zh) * 2015-09-30 2019-04-02 华中农业大学 一种利用内源CRISPR-Cas系统进行原核生物基因组编辑的方法
US11970710B2 (en) 2015-10-13 2024-04-30 Duke University Genome engineering with Type I CRISPR systems in eukaryotic cells
EP3365357B1 (en) 2015-10-23 2024-02-14 President and Fellows of Harvard College Evolved cas9 proteins for gene editing
ES2699848T3 (es) 2015-10-23 2019-02-13 Caribou Biosciences Inc Acido nucleico CRISPR clase 2 de tipo cruzado modificado que se dirige a ácidos nucleicos
JP6882282B2 (ja) 2015-11-03 2021-06-02 プレジデント アンド フェローズ オブ ハーバード カレッジ 三次元核酸含有マトリックスの立体撮像のための方法と装置
EP3382019B1 (en) 2015-11-27 2022-05-04 National University Corporation Kobe University Method for converting monocot plant genome sequence in which nucleic acid base in targeted dna sequence is specifically converted, and molecular complex used therein
WO2017112620A1 (en) 2015-12-22 2017-06-29 North Carolina State University Methods and compositions for delivery of crispr based antimicrobials
BR112018013663A2 (pt) 2016-01-11 2019-01-22 Univ Leland Stanford Junior proteínas quiméricas e métodos de imunoterapia
MY196175A (en) 2016-01-11 2023-03-20 Univ Leland Stanford Junior Chimeric Proteins And Methods Of Regulating Gene Expression
CN108884448B (zh) 2016-01-27 2022-12-30 昂克诺斯公司 溶瘤病毒载体及其用途
EP3433364A1 (en) 2016-03-25 2019-01-30 Editas Medicine, Inc. Systems and methods for treating alpha 1-antitrypsin (a1at) deficiency
US11597924B2 (en) 2016-03-25 2023-03-07 Editas Medicine, Inc. Genome editing systems comprising repair-modulating enzyme molecules and methods of their use
WO2017180694A1 (en) 2016-04-13 2017-10-19 Editas Medicine, Inc. Cas9 fusion molecules gene editing systems, and methods of use thereof
EP3449016A4 (en) 2016-04-25 2019-10-02 President and Fellows of Harvard College HYBRIDIZATION CHAIN REACTION PROCESS FOR IN-SITU MOLECULE DETECTION
EP3458595A2 (en) 2016-05-18 2019-03-27 Amyris, Inc. Compositions and methods for genomic integration of nucleic acids into exogenous landing pads
EP3907286A1 (en) 2016-06-02 2021-11-10 Sigma-Aldrich Co., LLC Using programmable dna binding proteins to enhance targeted genome modification
US10767175B2 (en) 2016-06-08 2020-09-08 Agilent Technologies, Inc. High specificity genome editing using chemically modified guide RNAs
EP3472311A4 (en) * 2016-06-17 2020-03-04 Montana State University BIDIRECTIONAL TARGETING FOR GENOMEDITATION
CA3032822A1 (en) 2016-08-02 2018-02-08 Editas Medicine, Inc. Compositions and methods for treating cep290 associated disease
AU2017306676B2 (en) 2016-08-03 2024-02-22 President And Fellows Of Harvard College Adenosine nucleobase editors and uses thereof
US11078481B1 (en) 2016-08-03 2021-08-03 KSQ Therapeutics, Inc. Methods for screening for cancer targets
AU2017308889B2 (en) 2016-08-09 2023-11-09 President And Fellows Of Harvard College Programmable Cas9-recombinase fusion proteins and uses thereof
US11542509B2 (en) 2016-08-24 2023-01-03 President And Fellows Of Harvard College Incorporation of unnatural amino acids into proteins using base editing
US11078483B1 (en) 2016-09-02 2021-08-03 KSQ Therapeutics, Inc. Methods for measuring and improving CRISPR reagent function
US20190225974A1 (en) 2016-09-23 2019-07-25 BASF Agricultural Solutions Seed US LLC Targeted genome optimization in plants
CN110290813A (zh) 2016-10-14 2019-09-27 通用医疗公司 表观遗传学调控的位点特异性核酸酶
SG11201903089RA (en) 2016-10-14 2019-05-30 Harvard College Aav delivery of nucleobase editors
WO2018075664A1 (en) 2016-10-18 2018-04-26 Regents Of The University Of Minnesota Tumor infiltrating lymphocytes and methods of therapy
US9816093B1 (en) 2016-12-06 2017-11-14 Caribou Biosciences, Inc. Engineered nucleic acid-targeting nucleic acids
WO2018119359A1 (en) 2016-12-23 2018-06-28 President And Fellows Of Harvard College Editing of ccr5 receptor gene to protect against hiv infection
US11230710B2 (en) 2017-01-09 2022-01-25 Aposense Ltd Compounds and methods for trans-membrane delivery of molecules
US11866699B2 (en) 2017-02-10 2024-01-09 University Of Washington Genome editing reagents and their use
WO2018165504A1 (en) 2017-03-09 2018-09-13 President And Fellows Of Harvard College Suppression of pain by gene editing
US11542496B2 (en) 2017-03-10 2023-01-03 President And Fellows Of Harvard College Cytosine to guanine base editor
EP3596217A1 (en) 2017-03-14 2020-01-22 Editas Medicine, Inc. Systems and methods for the treatment of hemoglobinopathies
WO2018170436A1 (en) 2017-03-16 2018-09-20 Jacobs Farm Del Cabo Basil with high tolerance to downy mildew
IL306092A (en) 2017-03-23 2023-11-01 Harvard College Nucleic base editors that include nucleic acid programmable DNA binding proteins
PT3526324T (pt) 2017-03-28 2021-10-20 Locanabio Inc Proteína associada a crispr (cas)
WO2018195545A2 (en) 2017-04-21 2018-10-25 The General Hospital Corporation Variants of cpf1 (cas12a) with altered pam specificity
EP3615672A1 (en) 2017-04-28 2020-03-04 Editas Medicine, Inc. Methods and systems for analyzing guide rna molecules
EP3622070A2 (en) 2017-05-10 2020-03-18 Editas Medicine, Inc. Crispr/rna-guided nuclease systems and methods
WO2018209320A1 (en) 2017-05-12 2018-11-15 President And Fellows Of Harvard College Aptazyme-embedded guide rnas for use with crispr-cas9 in genome editing and transcriptional activation
WO2018218166A1 (en) 2017-05-25 2018-11-29 The General Hospital Corporation Using split deaminases to limit unwanted off-target base editor deamination
KR102541398B1 (ko) * 2017-06-08 2023-06-07 고꾸리쯔 다이가꾸 호우징 오사까 다이가꾸 Dna가 편집된 진핵 세포를 제조하는 방법 및 당해 방법에 사용되는 키트
EP3635104A1 (en) 2017-06-09 2020-04-15 Editas Medicine, Inc. Engineered cas9 nucleases
WO2018232356A1 (en) 2017-06-15 2018-12-20 The Regents Of The University Of California Targeted non-viral dna insertions
EP3650545A4 (en) 2017-06-20 2021-03-31 Jiangsu Hengrui Medicine Co., Ltd. METHOD OF INACTIVATION OF A TARGET GENE IN T CELLS IN VITRO AND ARNCR USED IN THE PROCESS
WO2019006418A2 (en) 2017-06-30 2019-01-03 Intima Bioscience, Inc. ADENO-ASSOCIATED VIRAL VECTORS FOR GENE THERAPY
WO2019014564A1 (en) 2017-07-14 2019-01-17 Editas Medicine, Inc. SYSTEMS AND METHODS OF TARGETED INTEGRATION AND GENOME EDITING AND DETECTION THEREOF WITH INTEGRATED PRIMING SITES
EP3658165A4 (en) 2017-07-26 2021-09-01 Oncorus, Inc. ONCOLYTIC VIRUS VECTORS AND USES THEREOF
JP2020534795A (ja) 2017-07-28 2020-12-03 プレジデント アンド フェローズ オブ ハーバード カレッジ ファージによって支援される連続的進化（ｐａｃｅ）を用いて塩基編集因子を進化させるための方法および組成物
CN111247247A (zh) 2017-08-21 2020-06-05 国立大学法人德岛大学 使用核苷酸靶识别的靶序列特异性改变技术
JP2020532967A (ja) 2017-08-23 2020-11-19 ザ ジェネラル ホスピタル コーポレイション 変更されたＰＡＭ特異性を有する遺伝子操作されたＣＲＩＳＰＲ−Ｃａｓ９ヌクレアーゼ
WO2019139645A2 (en) 2017-08-30 2019-07-18 President And Fellows Of Harvard College High efficiency base editors comprising gam
US11917978B2 (en) 2017-09-21 2024-03-05 The Conard Pyle Company Miniature rose plant named ‘meibenbino’
US11252928B2 (en) 2017-09-21 2022-02-22 The Condard-Pyle Company Miniature rose plant named ‘Meibenbino’
EP3694993A4 (en) 2017-10-11 2021-10-13 The General Hospital Corporation METHOD OF DETECTING A SITE-SPECIFIC AND UNDESIRED GENOMIC DESAMINATION INDUCED BY BASE EDITING TECHNOLOGIES
US11795443B2 (en) 2017-10-16 2023-10-24 The Broad Institute, Inc. Uses of adenosine base editors
WO2019084552A1 (en) 2017-10-27 2019-05-02 The Regents Of The University Of California TARGETED REPLACEMENT OF ENDOGENIC T CELL RECEPTORS
WO2019138083A1 (en) 2018-01-12 2019-07-18 Basf Se Gene underlying the number of spikelets per spike qtl in wheat on chromosome 7a
US20210093679A1 (en) 2018-02-05 2021-04-01 Novome Biotechnologies, Inc. Engineered gut microbes and uses thereof
WO2019186275A1 (en) * 2018-03-27 2019-10-03 G+Flas Life Sciences Sequence-specific in vivo cell targeting
KR102023577B1 (ko) * 2018-03-27 2019-09-24 (주)지플러스 생명과학 가이드 rna 및 엔도뉴클레아제를 유효성분으로 포함하는 암 치료용 약학적 조성물
JP7422128B2 (ja) * 2018-04-03 2024-01-25 ジーフラス ライフ サイエンシズ，インク． 配列特異的なインビボ細胞標的化
WO2019204378A1 (en) 2018-04-17 2019-10-24 The General Hospital Corporation Sensitive in vitro assays for substrate preferences and sites of nucleic acid binding, modifying, and cleaving agents
GB2589246A (en) 2018-05-16 2021-05-26 Synthego Corp Methods and systems for guide RNA design and use
FR3082208A1 (fr) * 2018-06-11 2019-12-13 Fondation Mediterranee Infection Methode de modification d'une sequence cible d'acide nucleique d'une cellule hote
US20210102183A1 (en) * 2018-06-13 2021-04-08 Caribou Biosciences, Inc. Engineered cascade components and cascade complexes
SG11202010182SA (en) * 2018-06-13 2020-11-27 Caribou Biosciences Inc Engineered cascade components and cascade complexes
US10227576B1 (en) 2018-06-13 2019-03-12 Caribou Biosciences, Inc. Engineered cascade components and cascade complexes
WO2019246555A1 (en) * 2018-06-21 2019-12-26 Cornell University Type i crispr system as a tool for genome editing
EP3844273A1 (en) 2018-08-29 2021-07-07 Amyris, Inc. Cells and methods for selection based assay
GB201815820D0 (en) 2018-09-28 2018-11-14 Univ Wageningen Off-target activity inhibitors for guided endonucleases
US20220177943A1 (en) * 2018-10-01 2022-06-09 Rodolphe Barrangou 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
WO2020092725A1 (en) * 2018-11-01 2020-05-07 Montana State University Gene modulation with crispr system type i
US20210388333A1 (en) * 2018-11-09 2021-12-16 Inari Agriculture, Inc. Rna-guided nucleases and dna binding proteins
JP2022514493A (ja) 2018-12-14 2022-02-14 パイオニア ハイ－ブレッド インターナショナル， インコーポレイテッド ゲノム編集のための新規なｃｒｉｓｐｒ－ｃａｓシステム
US11946040B2 (en) 2019-02-04 2024-04-02 The General Hospital Corporation Adenine DNA base editor variants with reduced off-target RNA editing
WO2020176389A1 (en) 2019-02-25 2020-09-03 Caribou Biosciences, Inc. Plasmids for gene editing
JP2022526908A (ja) 2019-03-19 2022-05-27 ザ ブロード インスティテュート，インコーポレーテッド 編集ヌクレオチド配列を編集するための方法および組成物
US20220186263A1 (en) 2019-04-05 2022-06-16 Osaka University Method for producing knock-in cell
CN110438142A (zh) * 2019-05-13 2019-11-12 安徽大学 一种基于I-B-Svi型CRISPR-Cas系统中SviCas5-6-7的转录调控方法
WO2021092210A1 (en) * 2019-11-06 2021-05-14 Locus Biosciences, Inc. Phage compositions comprising crispr-cas systems and methods of use thereof
US20230022635A1 (en) * 2019-12-31 2023-01-26 Inari Agriculture Technology, Inc. Delivery of biological molecules to plant cells
CN115003825A (zh) * 2020-01-24 2022-09-02 Ｃ４Ｕ株式会社 检测试样中的特定dna的方法
AU2021267940A1 (en) 2020-05-08 2022-12-08 President And Fellows Of Harvard College Methods and compositions for simultaneous editing of both strands of a target double-stranded nucleotide sequence
CN111849978B (zh) * 2020-06-11 2022-04-15 中山大学 一种基于Type I-F CRISPR/Cas的染色质成像方法和染色质成像系统
CN111979240B (zh) * 2020-06-11 2022-04-15 中山大学 一种基于Type I-F CRISPR/Cas的基因表达调控方法和调控系统
IL301396A (en) 2020-09-30 2023-05-01 Nobell Foods Inc Recombinant milk proteins and food compositions containing them
US10894812B1 (en) 2020-09-30 2021-01-19 Alpine Roads, Inc. Recombinant milk proteins
US11944063B2 (en) 2020-09-30 2024-04-02 Spring Meadow Nursery, Inc. Hydrangea ‘SMNHPH’
US10947552B1 (en) 2020-09-30 2021-03-16 Alpine Roads, Inc. Recombinant fusion proteins for producing milk proteins in plants
EP3984355B1 (en) 2020-10-16 2024-05-15 Klemm & Sohn GmbH & Co. KG Double-flowering dwarf calibrachoa
US11155884B1 (en) 2020-10-16 2021-10-26 Klemm & Sohn Gmbh & Co. Kg Double-flowering dwarf Calibrachoa
WO2022093977A1 (en) 2020-10-30 2022-05-05 Fortiphyte, Inc. Pathogen resistance in plants
US20230407350A1 (en) 2020-11-10 2023-12-21 Industrial Microbes, Inc. Microorganisms capable of producing poly(hiba) from feedstock
CA3222023A1 (en) 2021-06-01 2022-12-08 Arbor Biotechnologies, Inc. Gene editing systems comprising a crispr nuclease and uses thereof
WO2023039491A2 (en) * 2021-09-09 2023-03-16 Proof Diagnostics, Inc. Coronavirus rapid diagnostics
AU2022343300A1 (en) 2021-09-10 2024-04-18 Agilent Technologies, Inc. Guide rnas with chemical modification for prime editing
US20230279442A1 (en) 2021-12-15 2023-09-07 Versitech Limited Engineered cas9-nucleases and method of use thereof
CN117384867A (zh) * 2022-09-16 2024-01-12 北京普译生物科技有限公司 一种经修饰的Cas3移位酶及其应用
CN115851664B (zh) * 2022-09-19 2023-08-25 中国药科大学 一种I-B型CRISPR-Cascade-Cas3基因编辑系统及应用

Family Cites Families (124)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5034506A (en) 1985-03-15 1991-07-23 Anti-Gene Development Group Uncharged morpholino-based polymers having achiral intersubunit linkages
WO1988008450A1 (en) 1987-05-01 1988-11-03 Birdwell Finlayson Gene therapy for metabolite disorders
US5350689A (en) 1987-05-20 1994-09-27 Ciba-Geigy Corporation Zea mays plants and transgenic Zea mays plants regenerated from protoplasts or protoplast-derived cells
US5767367A (en) 1990-06-23 1998-06-16 Hoechst Aktiengesellschaft Zea mays (L.) with capability of long term, highly efficient plant regeneration including fertile transgenic maize plants having a heterologous gene, and their preparation
US5489677A (en) 1990-07-27 1996-02-06 Isis Pharmaceuticals, Inc. Oligonucleoside linkages containing adjacent oxygen and nitrogen atoms
US5602240A (en) 1990-07-27 1997-02-11 Ciba Geigy Ag. Backbone modified oligonucleotide analogs
FR2688514A1 (fr) 1992-03-16 1993-09-17 Centre Nat Rech Scient Adenovirus recombinants defectifs exprimant des cytokines et medicaments antitumoraux les contenant.
US5625048A (en) 1994-11-10 1997-04-29 The Regents Of The University Of California Modified green fluorescent proteins
US5968738A (en) 1995-12-06 1999-10-19 The Board Of Trustees Of The Leland Stanford Junior University Two-reporter FACS analysis of mammalian cells using green fluorescent proteins
US20020182673A1 (en) 1998-05-15 2002-12-05 Genentech, Inc. IL-17 homologous polypedies and therapeutic uses thereof
US6306610B1 (en) 1998-09-18 2001-10-23 Massachusetts Institute Of Technology Biological applications of quantum dots
EP1147209A2 (en) 1999-02-03 2001-10-24 The Children's Medical Center Corporation Gene repair involving the induction of double-stranded dna cleavage at a chromosomal target site
AU784151B2 (en) 1999-12-28 2006-02-09 Ribonomics, Inc. Methods for isolating and characterizing endogenous mRNA-protein (mRNP) complexes
US20020119570A1 (en) 2000-09-25 2002-08-29 Kyonggeun Yoon Targeted gene correction by single-stranded oligodeoxynucleotides
MXPA03003690A (es) 2000-10-27 2004-05-05 Chiron Spa Acidos nucleicos y proteinas de los grupos a y b de estreptococos.
US20060253913A1 (en) 2001-12-21 2006-11-09 Yue-Jin Huang Production of hSA-linked butyrylcholinesterases in transgenic mammals
CA2474486C (en) 2002-01-23 2013-05-14 The University Of Utah Research Foundation Targeted chromosomal mutagenesis using zinc finger nucleases
US20030232410A1 (en) 2002-03-21 2003-12-18 Monika Liljedahl Methods and compositions for using zinc finger endonucleases to enhance homologous recombination
US7539579B2 (en) 2002-04-09 2009-05-26 Beattie Kenneth L Oligonucleotide probes for genosensor chips
EP2806025B1 (en) 2002-09-05 2019-04-03 California Institute of Technology Use of zinc finger nucleases to stimulate gene targeting
US20120196370A1 (en) 2010-12-03 2012-08-02 Fyodor Urnov Methods and compositions for targeted genomic deletion
US7972854B2 (en) 2004-02-05 2011-07-05 Sangamo Biosciences, Inc. Methods and compositions for targeted cleavage and recombination
CN101426931A (zh) * 2004-04-07 2009-05-06 安克塞斯生物公司 核酸检测系统
US7919277B2 (en) 2004-04-28 2011-04-05 Danisco A/S Detection and typing of bacterial strains
US7892224B2 (en) 2005-06-01 2011-02-22 Brainlab Ag Inverse catheter planning
KR101419729B1 (ko) 2005-07-26 2014-07-17 상가모 바이오사이언스 인코포레이티드 외래 핵산 서열의 표적화된 통합 및 발현
DK2336362T3 (en) 2005-08-26 2019-01-21 Dupont Nutrition Biosci Aps USE OF CRISPR-ASSOCIATED GENES (CAS)
ATE513053T1 (de) 2006-05-10 2011-07-15 Deinove Sa Verfahren zur chromosomenmanipulation unter verwendung eines neuen dna-reparatursystems
ATE530669T1 (de) 2006-05-19 2011-11-15 Danisco Markierte mikroorganismen und entsprechende markierungsverfahren
WO2007139982A2 (en) 2006-05-25 2007-12-06 Sangamo Biosciences, Inc. Methods and compositions for gene inactivation
PL2034848T3 (pl) 2006-06-16 2017-08-31 Dupont Nutrition Bioscences Aps Bakteria Streptococcus thermophilus
WO2008019123A2 (en) 2006-08-04 2008-02-14 Georgia State University Research Foundation, Inc. Enzyme sensors, methods for preparing and using such sensors, and methods of detecting protease activity
WO2008108989A2 (en) 2007-03-02 2008-09-12 Danisco A/S Cultures with improved phage resistance
EP2142673B1 (en) * 2007-04-05 2013-05-22 Johnson & Johnson Research Pty Limited Nucleic acid enzymes and complexes and methods for their use
FR2925918A1 (fr) 2007-12-28 2009-07-03 Pasteur Institut Typage et sous-typage moleculaire de salmonella par identification des sequences nucleotidiques variables des loci crispr
US8546553B2 (en) 2008-07-25 2013-10-01 University Of Georgia Research Foundation, Inc. Prokaryotic RNAi-like system and methods of use
CN102159722B (zh) 2008-08-22 2014-09-03 桑格摩生物科学股份有限公司 用于靶向单链切割和靶向整合的方法和组合物
EP3208339B1 (en) 2008-09-15 2019-05-01 The Children's Medical Center Corporation Modulation of bcl11a for treatment of hemoglobinopathies
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
MX337838B (es) 2008-11-07 2016-03-22 Dupont Nutrition Biosci Aps Secuencias de repetidos palindromicos cortos regularmente intercalados agrupados de bifidobacterias.
PT2367938E (pt) 2008-12-12 2014-09-05 Dupont Nutrition Biosci Aps Agrupamento genético de estirpes de streptococcus thermophilus com propriedades reológicas únicas para a fermentação de lacticínios
WO2010075424A2 (en) 2008-12-22 2010-07-01 The Regents Of University Of California Compositions and methods for downregulating prokaryotic genes
CA2756833C (en) 2009-04-09 2019-11-19 Sangamo Biosciences, Inc. Targeted integration into stem cells
ES2786039T3 (es) 2009-04-30 2020-10-08 Ospedale San Raffaele Srl Vector génico
JP2012529287A (ja) 2009-06-11 2012-11-22 トゥールゲン インコーポレイション 部位−特異的ヌクレアーゼを用いた標的ゲノムの再配列
SG177711A1 (en) 2009-07-24 2012-02-28 Sigma Aldrich Co Llc Method for genome editing
US20120192298A1 (en) 2009-07-24 2012-07-26 Sigma Aldrich Co. Llc Method for genome editing
US9234016B2 (en) 2009-07-28 2016-01-12 Sangamo Biosciences, Inc. Engineered zinc finger proteins for treating trinucleotide repeat disorders
WO2011019385A1 (en) 2009-08-11 2011-02-17 Sangamo Biosciences, Inc. Organisms homozygous for targeted modification
EP2292731B1 (en) 2009-08-13 2018-04-04 DuPont Nutrition Biosciences ApS Method for preparing complex cultures
EA201290168A1 (ru) 2009-09-25 2013-10-30 Басф Плант Сайенс Компани Гмбх Растения, обладающие повышенными урожайностными свойствами, и способ создания таких растений
US20110105364A1 (en) 2009-11-02 2011-05-05 Nugen Technologies, Inc. Compositions and methods for targeted nucleic acid sequence selection and amplification
BR112012012444A2 (pt) 2009-11-27 2015-09-22 Basf Plant Science Co Gmbh "endonuclease quimérica, polinucleotídeo isolado, cassete de expressão, vetor, organismo não humano, método para fornecer uma endonuclease quimérica, método para recombinação homóloga de polinucleotídeos, método para mutação alvejada de polinucleotídeosa e método para recombinação homóloga ou mutação alvejada"
US20110294114A1 (en) 2009-12-04 2011-12-01 Cincinnati Children's Hospital Medical Center Optimization of determinants for successful genetic correction of diseases, mediated by hematopoietic stem cells
SG181601A1 (en) 2009-12-10 2012-07-30 Univ Minnesota Tal effector-mediated dna modification
US20110203012A1 (en) 2010-01-21 2011-08-18 Dotson Stanton B Methods and compositions for use of directed recombination in plant breeding
CA2788560A1 (en) * 2010-02-08 2011-08-11 Sangamo Biosciences, Inc. Engineered cleavage half-domains
US9255259B2 (en) 2010-02-09 2016-02-09 Sangamo Biosciences, 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
US20130059388A1 (en) 2010-04-13 2013-03-07 Sigma-Aldrich Co., Llc Methods for generating endogenously tagged proteins
SG185481A1 (en) 2010-05-10 2012-12-28 Univ California Endoribonuclease compositions and methods of use thereof
EP2571512B1 (en) 2010-05-17 2017-08-23 Sangamo BioSciences, Inc. Novel dna-binding proteins and uses thereof
WO2011156430A2 (en) 2010-06-07 2011-12-15 Fred Hutchinson Cancer Research Center Generation and expression of engineered i-onui endonuclease and its homologues and uses thereof
EP2392208B1 (en) * 2010-06-07 2016-05-04 Helmholtz Zentrum München Deutsches Forschungszentrum für Gesundheit und Umwelt (GmbH) Fusion proteins comprising a DNA-binding domain of a Tal effector protein and a non-specific cleavage domain of a restriction nuclease and their use
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
EP2601611B1 (en) 2010-08-02 2020-12-09 Integrated Dna Technologies, Inc. Methods for predicting stability and melting temperatures of nucleic acid duplexes
EP2630156B1 (en) 2010-10-20 2018-08-22 DuPont Nutrition Biosciences ApS Lactococcus crispr-cas sequences
KR20120096395A (ko) 2011-02-22 2012-08-30 주식회사 툴젠 뉴클레아제에 의해 유전자 변형된 세포를 농축시키는 방법
US20140123330A1 (en) 2012-10-30 2014-05-01 Recombinetics, Inc. Control of sexual maturation in animals
CA2834375C (en) 2011-04-27 2020-07-14 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
US8927218B2 (en) 2011-06-27 2015-01-06 Flir Systems, Inc. Methods and compositions for segregating target nucleic acid from mixed nucleic acid samples
CN103917644A (zh) 2011-09-21 2014-07-09 桑格摩生物科学股份有限公司 调控转基因表达的方法和组合物
US8450107B1 (en) 2011-11-30 2013-05-28 The Broad Institute Inc. Nucleotide-specific recognition sequences for designer TAL effectors
IN2014MN00974A (ru) 2011-12-16 2015-04-24 Targetgene Biotechnologies Ltd
GB201122458D0 (en) 2011-12-30 2012-02-08 Univ Wageningen Modified cascade ribonucleoproteins and uses thereof
EP3272356A1 (en) 2012-02-24 2018-01-24 Fred Hutchinson Cancer Research Center Compositions and methods for the treatment of hemoglobinopathies
JP6490426B2 (ja) 2012-02-29 2019-03-27 サンガモ セラピューティクス， インコーポレイテッド ハンチントン病を治療するための方法および組成物
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
US11518997B2 (en) 2012-04-23 2022-12-06 BASF Agricultural Solutions Seed US LLC Targeted genome engineering in plants
MX369788B (es) 2012-05-02 2019-11-21 Dow Agrosciences Llc Modificacion dirigida de deshidrogenasa de malato.
RU2650819C2 (ru) 2012-05-07 2018-04-17 Сангамо Терапьютикс, Инк. Способы и композиции для опосредованной нуклеазой направленной интеграции трансгенов
US11120889B2 (en) 2012-05-09 2021-09-14 Georgia Tech Research Corporation Method for synthesizing a nuclease with reduced off-site cleavage
LT3401400T (lt) * 2012-05-25 2019-06-10 The Regents Of The University Of California Būdai ir kompozicijos, skirtos rnr molekulės nukreipiamai tikslinės dnr modifikacijai ir rnr molekulės nukreipiamam transkripcijos moduliavimui
MX2014014650A (es) 2012-05-30 2015-10-14 Univ Washington Minivectores superenrollados como una herramienta para la reparacion, alteración y reemplazo de ácido desoxirribonucleico.
WO2013188037A2 (en) 2012-06-11 2013-12-19 Agilent Technologies, Inc Method of adaptor-dimer subtraction using a crispr cas6 protein
CN104540382A (zh) 2012-06-12 2015-04-22 弗·哈夫曼-拉罗切有限公司 用于产生条件性敲除等位基因的方法和组合物
EP2674501A1 (en) 2012-06-14 2013-12-18 Agence nationale de sécurité sanitaire de l'alimentation,de l'environnement et du travail Method for detecting and identifying enterohemorrhagic Escherichia coli
US9688971B2 (en) 2012-06-15 2017-06-27 The Regents Of The University Of California Endoribonuclease and methods of use thereof
EP2861737B1 (en) 2012-06-19 2019-04-17 Regents Of The University Of Minnesota Gene targeting in plants using dna viruses
HUE041553T2 (hu) 2012-07-11 2019-05-28 Sangamo Therapeutics Inc Lizoszomális tárolási betegségek (LSD) kezelése és génterápia
CA2878037C (en) 2012-07-11 2021-08-31 Sangamo Biosciences, Inc. Methods and compositions for delivery of biologics
PT3494997T (pt) 2012-07-25 2019-12-05 Massachusetts Inst Technology Proteínas de ligação a adn indutíveis e ferramentas de perturbação do genoma e aplicações destas
ES2812599T3 (es) 2012-08-29 2021-03-17 Sangamo Therapeutics Inc Procedimientos y composiciones para el tratamiento de una afección genética
UA119135C2 (uk) 2012-09-07 2019-05-10 ДАУ АГРОСАЙЄНСІЗ ЕлЕлСі Спосіб отримання трансгенної рослини
CN105264067B (zh) 2012-09-07 2020-11-10 美国陶氏益农公司 Fad3性能基因座及相应的能够诱导靶向断裂的靶位点特异性结合蛋白
UA118090C2 (uk) 2012-09-07 2018-11-26 ДАУ АГРОСАЙЄНСІЗ ЕлЕлСі Спосіб інтегрування послідовності нуклеїнової кислоти, що представляє інтерес, у ген fad2 у клітині сої та специфічний для локусу fad2 білок, що зв'язується, здатний індукувати спрямований розрив
EP2906602B1 (en) 2012-10-12 2019-01-16 The General Hospital Corporation Transcription activator-like effector (tale) - lysine-specific demethylase 1 (lsd1) fusion proteins
DE202013012597U1 (de) 2012-10-23 2017-11-21 Toolgen, Inc. Zusammensetzung zum Spalten einer Ziel-DNA, umfassend eine für die Ziel-DNA spezifische guide-RNA und eine Cas-Protein-codierende Nukleinsäure oder ein Cas-Protein, sowie deren Verwendung
US20150291967A1 (en) 2012-10-31 2015-10-15 Luc Mathis Coupling herbicide resistance with targeted insertion of transgenes in plants
US20140127752A1 (en) 2012-11-07 2014-05-08 Zhaohui Zhou Method, composition, and reagent kit for targeted genomic enrichment
EP3138911B1 (en) * 2012-12-06 2018-12-05 Sigma Aldrich Co. LLC Crispr-based genome modification and regulation
ES2658401T3 (es) 2012-12-12 2018-03-09 The Broad Institute, Inc. Suministro, modificación y optimización de sistemas, métodos y composiciones para la manipulación de secuencias y aplicaciones terapéuticas
EP2931892B1 (en) 2012-12-12 2018-09-12 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
EP2931899A1 (en) 2012-12-12 2015-10-21 The Broad Institute, Inc. Functional genomics using crispr-cas systems, compositions, methods, knock out libraries and applications thereof
WO2014093694A1 (en) 2012-12-12 2014-06-19 The Broad Institute, Inc. Crispr-cas nickase systems, methods and compositions for sequence manipulation in eukaryotes
ES2576128T3 (es) 2012-12-12 2016-07-05 The Broad Institute, Inc. Modificación por tecnología genética y optimización de sistemas, métodos y composiciones para la manipulación de secuencias con dominios funcionales
US8697359B1 (en) 2012-12-12 2014-04-15 The Broad Institute, Inc. CRISPR-Cas systems and methods for altering expression of gene products
PL2784162T3 (pl) 2012-12-12 2016-01-29 Broad Inst Inc Opracowanie systemów, metod oraz zoptymalizowanych kompozycji przewodnikowych do manipulacji sekwencyjnej
EP4234696A3 (en) 2012-12-12 2023-09-06 The Broad Institute Inc. Crispr-cas component systems, methods and compositions for sequence manipulation
PT2921557T (pt) 2012-12-12 2016-10-19 Massachusetts Inst Technology Engenharia de sistemas, métodos e composições guia otimizadas para a manipulação de sequências
DK2898075T3 (en) 2012-12-12 2016-06-27 Broad Inst Inc CONSTRUCTION AND OPTIMIZATION OF IMPROVED SYSTEMS, PROCEDURES AND ENZYME COMPOSITIONS FOR SEQUENCE MANIPULATION
CA3081054A1 (en) 2012-12-17 2014-06-26 President And Fellows Of Harvard College Rna-guided human genome engineering
WO2014104878A1 (en) 2012-12-27 2014-07-03 Keygene N.V. Method for removing genetic linkage in a plant
AU2014207618A1 (en) 2013-01-16 2015-08-06 Emory University Cas9-nucleic acid complexes and uses related thereto
CN103233028B (zh) 2013-01-25 2015-05-13 南京徇齐生物技术有限公司 一种无物种限制无生物安全性问题的真核生物基因打靶方法及螺旋结构dna序列
CA2906553C (en) * 2013-03-15 2022-08-02 The General Hospital Corporation Rna-guided targeting of genetic and epigenomic regulatory proteins to specific genomic loci
CN103224947B (zh) 2013-04-28 2015-06-10 陕西师范大学 一种基因打靶系统
EP3417880A1 (en) * 2013-06-05 2018-12-26 Duke University Rna-guided gene editing and gene regulation
CN103343120B (zh) 2013-07-04 2015-03-04 中国科学院遗传与发育生物学研究所 一种小麦基因组定点改造方法
US10227576B1 (en) * 2018-06-13 2019-03-12 Caribou Biosciences, Inc. Engineered cascade components and cascade complexes

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