KR102531016B1 - 쌍 형성된 가이드 rna를 사용하는 표적화된 유전자 변형을 위한 방법 및 조성물 - Google Patents

쌍 형성된 가이드 rna를 사용하는 표적화된 유전자 변형을 위한 방법 및 조성물 Download PDF

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KR102531016B1
KR102531016B1 KR1020227021859A KR20227021859A KR102531016B1 KR 102531016 B1 KR102531016 B1 KR 102531016B1 KR 1020227021859 A KR1020227021859 A KR 1020227021859A KR 20227021859 A KR20227021859 A KR 20227021859A KR 102531016 B1 KR102531016 B1 KR 102531016B1
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cell
crispr rna
sequence
allele
cas protein
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KR20220093013A (ko
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앤써니 가글리아르디
구스타보 드로겟
카-만 비너스 라이
린 맥도날드
앤드류 제이. 머피
데이비드 엠. 발렌주엘라
베라 보로니나
보이테크 아우어바흐
조지 디. 얀코풀로스
데이비드 프렌듀이
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리제너론 파마슈티칼스 인코포레이티드
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KR1020227021859A 2014-11-21 2015-11-20 쌍 형성된 가이드 rna를 사용하는 표적화된 유전자 변형을 위한 방법 및 조성물 Active KR102531016B1 (ko)

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KR1020237015378A KR102683423B1 (ko) 2014-11-21 2015-11-20 쌍 형성된 가이드 rna를 사용하는 표적화된 유전자 변형을 위한 방법 및 조성물

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US201462083005P 2014-11-21 2014-11-21
US62/083,005 2014-11-21
US201562182314P 2015-06-19 2015-06-19
US62/182,314 2015-06-19
US201562211421P 2015-08-28 2015-08-28
US62/211,421 2015-08-28
PCT/US2015/062023 WO2016081923A2 (en) 2014-11-21 2015-11-20 METHODS AND COMPOSITIONS FOR TARGETED GENETIC MODIFICATION USING PAIRED GUIDE RNAs
KR1020177016481A KR102415093B1 (ko) 2014-11-21 2015-11-20 쌍 형성된 가이드 rna를 사용하는 표적화된 유전자 변형을 위한 방법 및 조성물

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KR1020177016481A Active KR102415093B1 (ko) 2014-11-21 2015-11-20 쌍 형성된 가이드 rna를 사용하는 표적화된 유전자 변형을 위한 방법 및 조성물
KR1020237015378A Active KR102683423B1 (ko) 2014-11-21 2015-11-20 쌍 형성된 가이드 rna를 사용하는 표적화된 유전자 변형을 위한 방법 및 조성물

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KR1020237015378A Active KR102683423B1 (ko) 2014-11-21 2015-11-20 쌍 형성된 가이드 rna를 사용하는 표적화된 유전자 변형을 위한 방법 및 조성물

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US (4) US10457960B2 (https=)
EP (2) EP3521437B1 (https=)
JP (2) JP6727199B2 (https=)
KR (3) KR102531016B1 (https=)
CN (2) CN107208078B (https=)
AU (2) AU2015349692B2 (https=)
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CA (2) CA3176380A1 (https=)
CY (1) CY1121738T1 (https=)
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Families Citing this family (139)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20050144655A1 (en) 2000-10-31 2005-06-30 Economides Aris N. Methods of modifying eukaryotic cells
US6596541B2 (en) 2000-10-31 2003-07-22 Regeneron Pharmaceuticals, Inc. Methods of modifying eukaryotic cells
WO2004106375A1 (en) 2003-05-30 2004-12-09 Merus Biopharmaceuticals B.V. I.O. Fab library for the preparation of anti vegf and anti rabies virus fabs
US20100069614A1 (en) 2008-06-27 2010-03-18 Merus B.V. Antibody producing non-human mammals
US10323236B2 (en) 2011-07-22 2019-06-18 President And Fellows Of Harvard College Evaluation and improvement of nuclease cleavage specificity
WO2013163628A2 (en) 2012-04-27 2013-10-31 Duke University Genetic correction of mutated genes
MX384291B (es) 2013-02-20 2025-03-14 Regeneron Pharma Modificación genética de ratas.
US9828582B2 (en) 2013-03-19 2017-11-28 Duke University Compositions and methods for the induction and tuning of gene expression
DK3456831T3 (da) 2013-04-16 2021-09-06 Regeneron Pharma Målrettet modifikation af rottegenom
US9163284B2 (en) 2013-08-09 2015-10-20 President And Fellows Of Harvard College Methods for identifying a target site of a Cas9 nuclease
US9359599B2 (en) 2013-08-22 2016-06-07 President And Fellows Of Harvard College Engineered transcription activator-like effector (TALE) domains and uses thereof
US9322037B2 (en) 2013-09-06 2016-04-26 President And Fellows Of Harvard College Cas9-FokI fusion proteins and uses thereof
US9228207B2 (en) 2013-09-06 2016-01-05 President And Fellows Of Harvard College Switchable gRNAs comprising aptamers
US9526784B2 (en) 2013-09-06 2016-12-27 President And Fellows Of Harvard College Delivery system for functional nucleases
CN106459995B (zh) 2013-11-07 2020-02-21 爱迪塔斯医药有限公司 使用统治型gRNA的CRISPR相关方法和组合物
KR102170502B1 (ko) 2013-12-11 2020-10-28 리제너론 파마슈티칼스 인코포레이티드 게놈의 표적화된 변형을 위한 방법 및 조성물
US20150165054A1 (en) 2013-12-12 2015-06-18 President And Fellows Of Harvard College Methods for correcting caspase-9 point mutations
HRP20200529T1 (hr) 2014-06-06 2020-09-04 Regeneron Pharmaceuticals, Inc. Postupci i pripravci za modificiranje ciljnog lokusa
SI3161128T1 (sl) 2014-06-26 2019-02-28 Regeneron Pharmaceuticals, Inc. Postopki in sestavki za ciljano genetsko spremembo in postopki uporabe
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
BR112017007770A2 (pt) 2014-10-15 2018-01-16 Regeneron Pharma cultura in vitro, população de hipscs, método para modificar um locus-alvo genômico, e, hipsc.
EP4464338A3 (en) 2014-11-07 2025-02-12 Editas Medicine, Inc. Systems for improving crispr/cas-mediated genome-editing
KR102531016B1 (ko) 2014-11-21 2023-05-10 리제너론 파마슈티칼스 인코포레이티드 쌍 형성된 가이드 rna를 사용하는 표적화된 유전자 변형을 위한 방법 및 조성물
ES2947714T3 (es) 2014-12-19 2023-08-17 Regeneron Pharma Métodos y composiciones para la modificación genética dirigida a través de múltiples direccionamientos en un solo paso
WO2016130600A2 (en) 2015-02-09 2016-08-18 Duke University Compositions and methods for epigenome editing
CA2986310A1 (en) 2015-05-11 2016-11-17 Editas Medicine, Inc. Optimized crispr/cas9 systems and methods for gene editing in stem cells
AU2016270587B2 (en) 2015-05-29 2020-12-24 Regeneron Pharmaceuticals, Inc. Non-human animals having a disruption in a C9ORF72 locus
CN108026526B (zh) 2015-06-09 2023-05-12 爱迪塔斯医药公司 用于改善移植的crispr/cas相关方法和组合物
JP7044373B2 (ja) 2015-07-15 2022-03-30 ラトガース，ザ ステート ユニバーシティ オブ ニュージャージー ヌクレアーゼ非依存的な標的化遺伝子編集プラットフォームおよびその用途
EP3353296B1 (en) 2015-09-24 2020-11-04 Editas Medicine, Inc. Use of exonucleases to improve crispr/cas-mediated genome editing
EP4089175A1 (en) 2015-10-13 2022-11-16 Duke University Genome engineering with type i crispr systems in eukaryotic cells
IL310721B2 (en) 2015-10-23 2025-11-01 Harvard College Nucleobase editors and uses thereof
CN108471731A (zh) * 2015-11-06 2018-08-31 杰克逊实验室 大型基因组dna敲入及其用途
KR102787119B1 (ko) 2015-11-30 2025-03-27 듀크 유니버시티 유전자 편집에 의한 인간 디스트로핀 유전자의 교정을 위한 치료용 표적 및 사용 방법
KR20230006929A (ko) 2016-01-13 2023-01-11 리제너론 파마슈티칼스 인코포레이티드 조작된 중쇄 다양성 영역을 갖는 설치류
WO2017139505A2 (en) * 2016-02-11 2017-08-17 The Regents Of The University Of California Methods and compositions for modifying a mutant dystrophin gene in a cell's genome
US11597924B2 (en) 2016-03-25 2023-03-07 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
US20190127713A1 (en) 2016-04-13 2019-05-02 Duke University Crispr/cas9-based repressors for silencing gene targets in vivo and methods of use
CN113831407B (zh) * 2016-05-20 2024-06-11 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
US20210010022A1 (en) * 2016-05-27 2021-01-14 Cambridge Enterprise Limited Novel nucleic acid construct
US20190323038A1 (en) * 2016-06-17 2019-10-24 Montana State Univesity Bidirectional targeting for genome editing
EP3472338B1 (en) * 2016-06-20 2024-05-22 Octapharma AG Means and methods for modifying multiple alleles
WO2018001241A1 (zh) * 2016-06-28 2018-01-04 北京百奥赛图基因生物技术有限公司 一种pd-1基因修饰人源化动物模型的构建方法及其应用
MA45670A (fr) * 2016-07-13 2019-05-22 Vertex Pharma Procédés, compositions et kits pour augmenter l'efficacité d'édition du génome
JP7490211B2 (ja) 2016-07-19 2024-05-27 デューク ユニバーシティ Ｃｐｆ１に基づくゲノム編集の治療適用
WO2017037304A2 (en) * 2016-07-28 2017-03-09 Dsm Ip Assets B.V. An assembly system for a eukaryotic cell
JP2019523009A (ja) 2016-07-29 2019-08-22 リジェネロン・ファーマシューティカルズ・インコーポレイテッドＲｅｇｅｎｅｒｏｎ Ｐｈａｒｍａｃｅｕｔｉｃａｌｓ， Ｉｎｃ． Ｃ末端切断型フィブリリン−１の発現をもたらす変異を有するマウス
CN110214183A (zh) 2016-08-03 2019-09-06 哈佛大学的校长及成员们 腺苷核碱基编辑器及其用途
WO2018031683A1 (en) 2016-08-09 2018-02-15 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
CN109862785B (zh) 2016-09-30 2022-09-06 瑞泽恩制药公司 C9orf72基因座中具有六核苷酸重复扩增的非人类动物
KR102622411B1 (ko) 2016-10-14 2024-01-10 프레지던트 앤드 펠로우즈 오브 하바드 칼리지 핵염기 에디터의 aav 전달
SG10201913483XA (en) 2016-11-04 2020-03-30 Regeneron Pharma Non-human animals having an engineered immunoglobulin lambda light chain locus
CN106520831B (zh) * 2016-11-18 2020-05-26 青岛市畜牧兽医研究所 一种哺乳动物基因组修饰方法
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
EP3565608A4 (en) 2017-01-05 2020-12-16 Rutgers, The State University of New Jersey TARGETED GENE EDITING PLATFORM INDEPENDENT OF BICATENARY DNA BREAKAGE AND ITS USES
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
EP3583203B1 (en) 2017-02-15 2023-11-01 2seventy bio, Inc. Donor repair templates multiplex genome editing
EP3592853A1 (en) 2017-03-09 2020-01-15 President and Fellows of Harvard College Suppression of pain by gene editing
US12390514B2 (en) 2017-03-09 2025-08-19 President And Fellows Of Harvard College Cancer vaccine
US11542496B2 (en) 2017-03-10 2023-01-03 President And Fellows Of Harvard College Cytosine to guanine base editor
KR20240116572A (ko) 2017-03-23 2024-07-29 프레지던트 앤드 펠로우즈 오브 하바드 칼리지 핵산 프로그램가능한 dna 결합 단백질을 포함하는 핵염기 편집제
US11499151B2 (en) 2017-04-28 2022-11-15 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
WO2018213081A1 (en) * 2017-05-16 2018-11-22 Generos Biopharma Ltd. Compositions and methods for treating alzheimer's disease
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.
ES2996886T3 (en) 2017-06-27 2025-02-13 Regeneron Pharma Rodents comprising a humanized asgr1 locus
US11866726B2 (en) 2017-07-14 2024-01-09 Editas Medicine, Inc. Systems and methods for targeted integration and genome editing and detection thereof using integrated priming sites
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
CN110891420B (zh) 2017-07-31 2022-06-03 瑞泽恩制药公司 Cas转基因小鼠胚胎干细胞和小鼠及其应用
KR20200033259A (ko) 2017-07-31 2020-03-27 리제너론 파마슈티칼스 인코포레이티드 생체내에서 CRISPR/Cas-매개된 파괴 또는 삭제 및 외인성 도너 핵산과의 CRISPR/Cas-유도된 재조합을 평가하기 위한 방법 및 조성물
EP3676376B1 (en) 2017-08-30 2025-01-15 President and Fellows of Harvard College High efficiency base editors comprising gam
US20190098879A1 (en) 2017-09-29 2019-04-04 Regeneron Pharmaceuticals, Inc. Non-Human Animals Comprising A Humanized TTR Locus And Methods Of Use
WO2019072241A1 (en) 2017-10-13 2019-04-18 Beijing Biocytogen Co., Ltd NON-HUMAN ANIMAL GENETICALLY MODIFIED WITH PD-1 HUMAN OR CHIMERIC
KR20250107288A (ko) 2017-10-16 2025-07-11 더 브로드 인스티튜트, 인코퍼레이티드 아데노신 염기 편집제의 용도
JP7097440B2 (ja) 2017-11-10 2022-07-07 リジェネロン・ファーマシューティカルズ・インコーポレイテッド Ｓｌｃ３０ａ８変異を含む非ヒト動物および使用方法
JP7361031B2 (ja) 2017-11-30 2023-10-13 リジェネロン・ファーマシューティカルズ・インコーポレイテッド ヒト化ｔｒｋｂ遺伝子座を含む非ヒト動物
HUE060608T2 (hu) 2017-12-05 2023-03-28 Regeneron Pharma Genetikailag módosított immunglobulin lambda könnyûlánccal rendelkezõ egerek és azok alkalmazása
US12406749B2 (en) 2017-12-15 2025-09-02 The Broad Institute, Inc. Systems and methods for predicting repair outcomes in genetic engineering
BR112020013626A2 (pt) 2018-01-17 2020-12-01 Vertex Pharmaceuticals Incorporated compostos de quinoxalinona, composições, métodos e kits para aumentar a eficiência de edição de genoma
MA51619A (fr) 2018-01-17 2021-04-14 Vertex Pharma Inhibiteurs de la protéine kinase dépendante de l'adn
JP7466448B2 (ja) * 2018-01-17 2024-04-12 バーテックス ファーマシューティカルズ インコーポレイテッド Ｄｎａ－ｐｋ阻害剤
EP3740580A4 (en) 2018-01-19 2021-10-20 Duke University GENOME ENGINEERING WITH CRISPR-CAS SYSTEMS IN EUKARYONTS
US11643670B2 (en) 2018-01-29 2023-05-09 Massachusetts Institute Of Technology Methods of enhancing chromosomal homologous recombination
EP3592140A1 (en) 2018-03-19 2020-01-15 Regeneron Pharmaceuticals, Inc. Transcription modulation in animals using crispr/cas systems
JP7469806B2 (ja) 2018-03-29 2024-04-17 学校法人自治医科大学 ゲノム編集方法、組成物、細胞、細胞製剤、及び細胞製剤の製造方法
WO2019213183A1 (en) * 2018-04-30 2019-11-07 The Trustees Of The University Of Pennsylvania In utero crispr-mediated therapeutic editing of genes
WO2019216338A1 (ja) * 2018-05-08 2019-11-14 国立大学法人大阪大学 ホモ接合型細胞の作製方法
KR20210045360A (ko) 2018-05-16 2021-04-26 신테고 코포레이션 가이드 rna 설계 및 사용을 위한 방법 및 시스템
US12157760B2 (en) 2018-05-23 2024-12-03 The Broad Institute, Inc. Base editors and uses thereof
IL318469A (en) 2018-06-14 2025-03-01 Regeneron Pharma Non-human animals capable of reorganizing transgenic DH-DH, and their uses
EP3823633A4 (en) 2018-06-29 2023-05-03 Editas Medicine, Inc. SYNTHETIC LEAD MOLECULES, COMPOSITIONS AND METHODS RELATED THERETO
US12522807B2 (en) 2018-07-09 2026-01-13 The Broad Institute, Inc. RNA programmable epigenetic RNA modifiers and uses thereof
EP3844272A1 (en) 2018-08-28 2021-07-07 Flagship Pioneering Innovations VI, LLC Methods and compositions for modulating a genome
US11845958B2 (en) * 2018-09-05 2023-12-19 Wisconsin Alumni Research Foundation Genetically modified genes and cells, and methods of using same for silencing virus gene expression
WO2020050294A1 (ja) * 2018-09-05 2020-03-12 学校法人慶應義塾 相同組換え効率上昇剤及びその使用
JP7222075B2 (ja) 2018-09-13 2023-02-14 リジェネロン・ファーマシューティカルズ・インコーポレイテッド Ｃ３糸球体症のモデルとしての補体因子ｈ遺伝子ノックアウトラット
JP7250031B2 (ja) * 2018-09-25 2023-03-31 公益財団法人微生物化学研究会 新規ウイルスベクターおよびその製造方法と使用方法
WO2020092453A1 (en) 2018-10-29 2020-05-07 The Broad Institute, Inc. Nucleobase editors comprising geocas9 and uses thereof
KR102925054B1 (ko) 2018-12-20 2026-02-10 리제너론 파마슈티칼스 인코포레이티드 뉴클레아제-매개 반복부 팽창
US12351837B2 (en) 2019-01-23 2025-07-08 The Broad Institute, Inc. Supernegatively charged proteins and uses thereof
WO2020191233A1 (en) 2019-03-19 2020-09-24 The Broad Institute, Inc. Methods and compositions for editing nucleotide sequences
KR102661779B1 (ko) * 2019-04-04 2024-04-30 리제너론 파마슈티칼스 인코포레이티드 인간화 응고 인자 12 좌위를 포함하는 비-인간 동물
US12473543B2 (en) 2019-04-17 2025-11-18 The Broad Institute, Inc. Adenine base editors with reduced off-target effects
US11891618B2 (en) 2019-06-04 2024-02-06 Regeneron Pharmaceuticals, Inc. Mouse comprising a humanized TTR locus with a beta-slip mutation and methods of use
MX2021014893A (es) 2019-06-05 2022-03-11 Regeneron Pharma Animales no humanos que tienen un repertorio de cadena ligera lambda limitado expresado a partir del locus kappa y usos de estos.
MX2021015122A (es) 2019-06-07 2022-04-06 Regeneron Pharma Animales no humanos que comprenden un locus de albumina humanizado.
US12435330B2 (en) 2019-10-10 2025-10-07 The Broad Institute, Inc. Methods and compositions for prime editing RNA
WO2021108363A1 (en) 2019-11-25 2021-06-03 Regeneron Pharmaceuticals, Inc. Crispr/cas-mediated upregulation of humanized ttr allele
WO2021154791A1 (en) 2020-01-28 2021-08-05 Regeneron Pharmaceuticals, Inc. Non-human animals comprising a humanized pnpla3 locus and methods of use
EP4099821A1 (en) 2020-02-07 2022-12-14 Regeneron Pharmaceuticals, Inc. <smallcaps/>? ? ?klkb1? ? ? ? ?non-human animals comprising a humanizedlocus and methods of use
US20210292754A1 (en) * 2020-03-16 2021-09-23 Pairwise Plants Services, Inc. Natural guide architectures and methods of making and using the same
US20230102342A1 (en) 2020-03-23 2023-03-30 Regeneron Pharmaceuticals, Inc. Non-human animals comprising a humanized ttr locus comprising a v30m mutation and methods of use
JP6867635B1 (ja) * 2020-04-06 2021-04-28 株式会社Logomix ゲノム改変方法及びゲノム改変キット
EP4126224A4 (en) * 2020-04-27 2024-07-03 Duke University HIGH-THROUGHPUT SCREENING METHODS TO DISCOVER OPTIMAL GRNA PAIRS FOR CRISPR-MEDIATED EXON DELETION
IL297761A (en) 2020-05-08 2022-12-01 Broad Inst Inc Methods and compositions for simultaneously editing two helices of a designated double-helix nucleotide sequence
WO2021263146A2 (en) 2020-06-26 2021-12-30 Regeneron Pharmaceuticals, Inc. Non-human animals comprising a humanized ace2 locus
CN112481297A (zh) * 2020-11-02 2021-03-12 深圳先进技术研究院 一种制造染色体结构变异的方法
KR20220064170A (ko) 2020-11-11 2022-05-18 삼성전자주식회사 이미지 센서를 포함하는 전자 장치 및 그 동작 방법
CN112382339B (zh) * 2020-11-17 2024-08-13 中国人民解放军军事科学院军事医学研究院 一种识别合子型基因激活zga基因的方法及装置
CA3165366A1 (en) 2020-12-23 2022-06-30 Regeneron Pharmaceuticals, Inc. Nucleic acids encoding anchor modified antibodies and uses thereof
US20220389461A1 (en) * 2021-05-26 2022-12-08 Inscripta, Inc. Crispr editing in diploid genomes
CN113832189B (zh) * 2021-09-06 2022-10-21 中国人民解放军军事科学院军事医学研究院 一种用于敲除猪免疫球蛋白重链IGHG区的gRNA及其应用
US20250027116A1 (en) * 2021-09-24 2025-01-23 Immunocan Biotech Co. Ltd. Methods for large-size chromosomal transfer and modified chromosomes and organisims using same
US20250129390A1 (en) * 2021-09-30 2025-04-24 Osaka University Method for producing cell having dna deletion specific to one of homologous chromosomes
US20240415980A1 (en) 2021-10-28 2024-12-19 Regeneron Pharmaceuticals, Inc. Crispr/cas-related methods and compositions for knocking out c5
KR20240117571A (ko) 2021-12-08 2024-08-01 리제너론 파마슈티칼스 인코포레이티드 돌연변이 마이오실린 질환 모델 및 이의 용도
US20250049006A1 (en) 2021-12-20 2025-02-13 C/O Regeneron Pharmaceuticals, Inc. Non-human animals comprising humanized ace2 and tmprss loci
WO2023150798A1 (en) 2022-02-07 2023-08-10 Regeneron Pharmaceuticals, Inc. Compositions and methods for defining optimal treatment timeframes in lysosomal disease
AU2023218391A1 (en) 2022-02-11 2024-07-11 Regeneron Pharmaceuticals, Inc. Compositions and methods for screening 4r tau targeting agents
IL317874A (en) 2022-06-24 2025-02-01 Tune Therapeutics Inc Compounds, systems and methods for reducing low density lipoproteins through targeted gene suppression
EP4593590A1 (en) 2022-09-29 2025-08-06 Regeneron Pharmaceuticals, Inc. Correction of hepatosteatosis in humanized liver animals through restoration of il6/il6r/gp130 signaling in human hepatocytes
KR20250027489A (ko) * 2023-08-16 2025-02-26 기초과학연구원 단일가닥 절단 활성을 가지는 CRISPR/Cas 시스템과 PARP 억제제를 이용하는 세포 사멸 방법
WO2025250495A1 (en) 2024-05-28 2025-12-04 Regeneron Pharmaceuticals, Inc. Acceleration of human hepatocyte engraftment in humanized liver animals by supplementing paracrine ligands or agonists that activate human liver regeneration signals
WO2026005012A1 (ja) * 2024-06-28 2026-01-02 学校法人自治医科大学 インビトロ及びインビボのゲノム編集における相同組換えの効率を高める方法
WO2026064425A2 (en) 2024-09-17 2026-03-26 Dxome Co., Ltd. Mirror image crispr-cas compositions

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2014104878A1 (en) 2012-12-27 2014-07-03 Keygene N.V. Method for removing genetic linkage in a plant

Family Cites Families (180)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4516228A (en) 1983-08-25 1985-05-07 Mobil Oil Corporation Acoustic well logging device for detecting compressional and shear waves
US5830729A (en) 1996-04-18 1998-11-03 Institut Pasteur I Sce I-induced gene replacement and gene conversion in embryonic stem cells
AU8587598A (en) 1997-07-26 1999-02-16 Wisconsin Alumni Research Foundation Trans-species nuclear transfer
WO2000039316A1 (en) 1998-12-31 2000-07-06 The J. David Gladstone Institutes Transgenic rodents and rodent cell lines expressing hiv co-receptors
CA2361191A1 (en) 1999-02-03 2000-08-10 The Children's Medical Center Corporation Gene repair involving the induction of double-stranded dna cleavage at a chromosomal target site
AU776576B2 (en) 1999-12-06 2004-09-16 Sangamo Biosciences, Inc. Methods of using randomized libraries of zinc finger proteins for the identification of gene function
CA2410516A1 (en) 2000-05-31 2001-12-06 Chiron Corporation Compositions and methods for treating neoplastic disease using chemotherapy and radiation sensitizers
US7105348B2 (en) 2000-10-31 2006-09-12 Regeneron Pharmaceuticals, Inc. Methods of modifying eukaryotic cells
US20050144655A1 (en) 2000-10-31 2005-06-30 Economides Aris N. Methods of modifying eukaryotic cells
US6586251B2 (en) 2000-10-31 2003-07-01 Regeneron Pharmaceuticals, Inc. Methods of modifying eukaryotic cells
US6596541B2 (en) 2000-10-31 2003-07-22 Regeneron Pharmaceuticals, Inc. Methods of modifying eukaryotic cells
AUPR451401A0 (en) 2001-04-20 2001-05-24 Monash University A method of nuclear transfer
WO2003087341A2 (en) 2002-01-23 2003-10-23 The University Of Utah Research Foundation Targeted chromosomal mutagenesis using zinc finger nucleases
US7612250B2 (en) 2002-07-29 2009-11-03 Trustees Of Tufts College Nuclear transfer embryo formation method
US20030175968A1 (en) 2002-10-30 2003-09-18 Golic Kent G. Gene targeting method
EP1587545A2 (en) 2003-01-13 2005-10-26 Mahendra S. Rao Persistent expression of candidate molecule in proliferating stem and progenitor cells for delivery of therapeutic products
PL2305221T3 (pl) 2003-12-01 2015-11-30 Kudos Pharm Ltd Inhibitory naprawy uszkodzeń DNA w leczeniu raka
ES2463476T3 (es) 2004-10-19 2014-05-28 Regeneron Pharmaceuticals, Inc. Método para generar un ratón homocigótico para una modificación genética
FR2879622B1 (fr) 2004-12-17 2008-02-01 Agronomique Inst Nat Rech Procede in vitro de production d'ovocytes ou d'oeufs presentant une modification genomique ciblee
GB0615327D0 (en) 2006-03-30 2006-09-13 Univ Edinburgh Culture medium containing kinase inhibitors and uses thereof
AU2007235496B2 (en) 2006-03-31 2013-11-21 E. R. Squibb & Sons, L.L.C. Transgenic animals expressing chimeric antibodies for use in preparing human antibodies
CN101117633B (zh) 2006-08-03 2011-07-20 上海交通大学附属儿童医院 一种细胞核移植方法
US7771967B2 (en) 2006-12-22 2010-08-10 The J. David Gladstone Institutes Nucleic acid encoding apolipoprotein E-I3
DE602008003684D1 (de) 2007-04-26 2011-01-05 Sangamo Biosciences Inc Gezielte integration in die ppp1r12c-position
PL2602323T3 (pl) 2007-06-01 2018-06-29 Open Monoclonal Technology, Inc. Kompozycje i sposoby hamowania endogennych genów immunoglobin i wytwarzania transgenicznych ludzkich przeciwciał typu idiotypowego
SG191561A1 (en) 2008-08-22 2013-07-31 Sangamo Biosciences Inc Methods and compositions for targeted single-stranded cleavage and targeted integration
EP2352369B1 (en) 2008-12-04 2017-04-26 Sangamo BioSciences, Inc. Genome editing in rats using zinc-finger nucleases
US8586526B2 (en) 2010-05-17 2013-11-19 Sangamo Biosciences, Inc. DNA-binding proteins and uses thereof
JP5940977B2 (ja) 2009-08-11 2016-06-29 サンガモ バイオサイエンシーズ， インコーポレイテッド 標的改変によるホモ接合生物
US8518392B2 (en) 2009-08-14 2013-08-27 Regeneron Pharmaceuticals, Inc. Promoter-regulated differentiation-dependent self-deleting cassette
EP2493288B1 (en) 2009-10-28 2015-02-18 Helmholtz Zentrum München Deutsches Forschungszentrum für Gesundheit und Umwelt (GmbH) Homologous recombination in the oocyte
CA2779858C (en) 2009-10-29 2019-10-29 Regeneron Pharmaceuticals, Inc. Multifunctional alleles
WO2011053957A2 (en) 2009-11-02 2011-05-05 Gen9, Inc. Compositions and methods for the regulation of multiple genes of interest in a cell
EP2508595B1 (en) 2009-12-01 2016-11-23 National Cancer Center Method for constructing chimeric rat using rat embryonic stem cells
CN102791865B (zh) 2009-12-21 2015-07-01 凯津公司 用于转染原生质体的改进技术
PH12012501467B1 (en) 2010-01-22 2018-07-04 Corteva Agriscience Llc Excision of transgenes in genetically modified organisms
EP2660318A1 (en) 2010-02-09 2013-11-06 Sangamo BioSciences, Inc. Targeted genomic modification with partially single-stranded donor molecules
GB201009732D0 (en) 2010-06-10 2010-07-21 Gene Bridges Gmbh Direct cloning
MY191870A (en) 2010-06-11 2022-07-18 Regeneron Pharma Production of fertile xy female animals from xy es cells
AU2011281062B2 (en) 2010-07-21 2015-01-22 Board Of Regents, The University Of Texas System Methods and compositions for modification of a HLA locus
WO2012018726A1 (en) 2010-08-02 2012-02-09 Cellectis Sa Method for increasing double-strand break-induced gene targeting
WO2012129198A1 (en) 2011-03-23 2012-09-27 Transposagen Biopharmaceuticals, Inc. Genetically modified rat models for obesity and diabetes
WO2012168307A2 (en) 2011-06-07 2012-12-13 Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt (GmbH) Improved recombination efficiency by inhibition of nhej dna repair
CN107858333B (zh) 2011-10-28 2022-05-27 瑞泽恩制药公司 T细胞受体基因修饰小鼠
US9637739B2 (en) 2012-03-20 2017-05-02 Vilnius University RNA-directed DNA cleavage by the Cas9-crRNA complex
WO2013141680A1 (en) 2012-03-20 2013-09-26 Vilnius University RNA-DIRECTED DNA CLEAVAGE BY THE Cas9-crRNA COMPLEX
SG11201406547YA (en) 2012-04-25 2014-11-27 Regeneron Pharma Nuclease-mediated targeting with large targeting vectors
AU2013259647B2 (en) 2012-05-07 2018-11-08 Corteva Agriscience Llc Methods and compositions for nuclease-mediated targeted integration of transgenes
AU2013266968B2 (en) 2012-05-25 2017-06-29 Emmanuelle CHARPENTIER Methods and compositions for RNA-directed target DNA modification and for RNA-directed modulation of transcription
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
AU2013293270B2 (en) 2012-07-25 2018-08-16 Massachusetts Institute Of Technology Inducible DNA binding proteins and genome perturbation tools and applications thereof
JP5952141B2 (ja) * 2012-08-31 2016-07-13 京セラメディカル株式会社 人工心肺ポンプ用駆動装置
AU2013335451C1 (en) 2012-10-23 2024-07-04 Toolgen Incorporated Composition for cleaving a target DNA comprising a guide RNA specific for the target DNA and Cas protein-encoding nucleic acid or Cas protein, and use thereof
PL3360964T3 (pl) 2012-12-06 2020-03-31 Sigma-Aldrich Co. Llc Modyfikacja i regulacja genomu oparta na crispr
EP3031921B1 (en) 2012-12-12 2025-03-12 The Broad Institute, Inc. Delivery, engineering and optimization of systems, methods and compositions for sequence manipulation and therapeutic applications
US8697359B1 (en) 2012-12-12 2014-04-15 The Broad Institute, Inc. CRISPR-Cas systems and methods for altering expression of gene products
CN113355357B (zh) 2012-12-12 2024-12-03 布罗德研究所有限公司 对用于序列操纵的改进的系统、方法和酶组合物进行的工程化和优化
US20140310830A1 (en) * 2012-12-12 2014-10-16 Feng Zhang CRISPR-Cas Nickase Systems, Methods And Compositions For Sequence Manipulation in Eukaryotes
WO2014093655A2 (en) 2012-12-12 2014-06-19 The Broad Institute, Inc. Engineering and optimization of systems, methods and compositions for sequence manipulation with functional domains
EP2840140B2 (en) 2012-12-12 2023-02-22 The Broad Institute, Inc. Crispr-Cas based method for mutation of prokaryotic cells
DK2931891T3 (da) 2012-12-17 2019-08-19 Harvard College Rna-styret modificering af menneskelige genomer
WO2014127287A1 (en) 2013-02-14 2014-08-21 Massachusetts Institute Of Technology Method for in vivo tergated mutagenesis
MX384291B (es) 2013-02-20 2025-03-14 Regeneron Pharma Modificación genética de ratas.
US10227610B2 (en) 2013-02-25 2019-03-12 Sangamo Therapeutics, Inc. Methods and compositions for enhancing nuclease-mediated gene disruption
EP2922393B2 (en) 2013-02-27 2022-12-28 Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt (GmbH) Gene editing in the oocyte by cas9 nucleases
WO2014143381A1 (en) * 2013-03-09 2014-09-18 Agilent Technologies, Inc. Methods of in vivo engineering of large sequences using multiple crispr/cas selections of recombineering events
RU2662932C2 (ru) 2013-03-14 2018-07-31 Карибо Биосайенсиз, Инк. Композиции и способы с участием нуклеиновых кислот, нацеленных на нуклеиновые кислоты
US9234213B2 (en) 2013-03-15 2016-01-12 System Biosciences, Llc Compositions and methods directed to CRISPR/Cas genomic engineering systems
WO2014204578A1 (en) 2013-06-21 2014-12-24 The General Hospital Corporation Using rna-guided foki nucleases (rfns) to increase specificity for rna-guided genome editing
US20140273230A1 (en) 2013-03-15 2014-09-18 Sigma-Aldrich Co., Llc Crispr-based genome modification and regulation
US9937207B2 (en) 2013-03-21 2018-04-10 Sangamo Therapeutics, Inc. Targeted disruption of T cell receptor genes using talens
EP4286517A3 (en) 2013-04-04 2024-03-13 President and Fellows of Harvard College Therapeutic uses of genome editing with crispr/cas systems
US20160040155A1 (en) 2013-04-16 2016-02-11 University Of Washington Through Its Center For Commercialization Activating an alternative pathway for homology-directed repair to stimulate targeted gene correction and genome engineering
DK3456831T3 (da) 2013-04-16 2021-09-06 Regeneron Pharma Målrettet modifikation af rottegenom
US20160186208A1 (en) 2013-04-16 2016-06-30 Whitehead Institute For Biomedical Research Methods of Mutating, Modifying or Modulating Nucleic Acid in a Cell or Nonhuman Mammal
EP2796558A1 (en) 2013-04-23 2014-10-29 Rheinische Friedrich-Wilhelms-Universität Bonn Improved gene targeting and nucleic acid carrier molecule, in particular for use in plants
EP2994531B1 (en) 2013-05-10 2018-03-28 Sangamo Therapeutics, Inc. Delivery methods and compositions for nuclease-mediated genome engineering
AU2014273082B2 (en) 2013-05-29 2018-11-08 Cellectis A method for producing precise DNA cleavage using Cas9 nickase activity
US20140359795A1 (en) 2013-05-31 2014-12-04 Recombinetics, Inc. Genetic techniques for making animals with sortable sperm
US9982277B2 (en) 2013-06-11 2018-05-29 The Regents Of The University Of California Methods and compositions for target DNA modification
MX374532B (es) 2013-06-17 2025-03-06 Broad Inst Inc Suministro, uso y aplicaciones terapéuticas de los sistemas y composiciones crispr-cas, para actuar sobre trastornos y enfermedades utilizando componentes víricos.
RU2716420C2 (ru) 2013-06-17 2020-03-11 Те Брод Инститьют Инк. Доставка и применение систем crispr-cas, векторов и композиций для целенаправленного воздействия и терапии в печени
CN105492611A (zh) 2013-06-17 2016-04-13 布罗德研究所有限公司 用于序列操纵的优化的crispr-cas双切口酶系统、方法以及组合物
CN105683379A (zh) 2013-06-17 2016-06-15 布罗德研究所有限公司 用于对有丝分裂后细胞的疾病和障碍进行靶向和建模的系统、方法和组合物的递送、工程化和优化
WO2014204724A1 (en) 2013-06-17 2014-12-24 The Broad Institute Inc. Delivery, engineering and optimization of tandem guide systems, methods and compositions for sequence manipulation
WO2014204723A1 (en) 2013-06-17 2014-12-24 The Broad Institute Inc. Oncogenic models based on delivery and use of the crispr-cas systems, vectors and compositions
BR112015031639A2 (pt) 2013-06-19 2019-09-03 Sigma Aldrich Co Llc integração alvo
EP3019595A4 (en) 2013-07-09 2016-11-30 THERAPEUTIC USES OF A GENERIC CHANGE WITH CRISPR / CAS SYSTEMS
US11060083B2 (en) 2013-07-19 2021-07-13 Larix Bioscience Llc Methods and compositions for producing double allele knock outs
JP6482546B2 (ja) 2013-07-19 2019-03-13 ラリクス・バイオサイエンス・リミテッド・ライアビリティ・カンパニーＬａｒｉｘ Ｂｉｏｓｃｉｅｎｃｅ， Ｌｌｃ 二重対立遺伝子ノックアウトを生成するための方法および組成物
PL3024521T3 (pl) 2013-07-24 2019-05-31 Medic Activ Vertriebs Gmbh Nabój wymienny
US11306328B2 (en) 2013-07-26 2022-04-19 President And Fellows Of Harvard College Genome engineering
CN120574876A (zh) * 2013-08-22 2025-09-02 纳幕尔杜邦公司 使用向导rna/cas内切核酸酶系统的植物基因组修饰及其使用方法
JP7118588B2 (ja) 2013-08-29 2022-08-16 テンプル ユニヴァーシティ オブ ザ コモンウェルス システム オブ ハイヤー エデュケイション Ｈｉｖ感染のｒｎａガイド処置のための方法および組成物
EP3988649B1 (en) 2013-09-18 2024-11-27 Kymab Limited Methods, cells and organisms
WO2015048577A2 (en) 2013-09-27 2015-04-02 Editas Medicine, Inc. Crispr-related methods and compositions
WO2015048690A1 (en) 2013-09-27 2015-04-02 The Regents Of The University Of California Optimized small guide rnas and methods of use
WO2015052231A2 (en) 2013-10-08 2015-04-16 Technical University Of Denmark Multiplex editing system
EP3441468B1 (en) 2013-10-17 2021-05-19 Sangamo Therapeutics, Inc. Delivery methods and compositions for nuclease-mediated genome engineering
JP5900942B2 (ja) 2013-11-06 2016-04-06 国立大学法人広島大学 核酸挿入用ベクター
CN106459995B (zh) 2013-11-07 2020-02-21 爱迪塔斯医药有限公司 使用统治型gRNA的CRISPR相关方法和组合物
US10787684B2 (en) 2013-11-19 2020-09-29 President And Fellows Of Harvard College Large gene excision and insertion
JP2016538001A (ja) 2013-11-28 2016-12-08 ホライズン・ジェノミクス・ゲーエムベーハー 体細胞半数体ヒト細胞株
KR102170502B1 (ko) 2013-12-11 2020-10-28 리제너론 파마슈티칼스 인코포레이티드 게놈의 표적화된 변형을 위한 방법 및 조성물
SG10201804975PA (en) 2013-12-12 2018-07-30 Broad Inst Inc Delivery, Use and Therapeutic Applications of the Crispr-Cas Systems and Compositions for HBV and Viral Diseases and Disorders
JP7103750B2 (ja) 2013-12-12 2022-07-20 ザ・ブロード・インスティテュート・インコーポレイテッド ゲノム編集のためのＣＲＩＳＰＲ－Ｃａｓ系及び組成物の送達、使用及び治療適用
EP3470089A1 (en) 2013-12-12 2019-04-17 The Broad Institute Inc. Delivery, use and therapeutic applications of the crispr-cas systems and compositions for targeting disorders and diseases using particle delivery components
EP3080259B1 (en) 2013-12-12 2023-02-01 The Broad Institute, Inc. Engineering of systems, methods and optimized guide compositions with new architectures for sequence manipulation
JP6712948B2 (ja) 2013-12-12 2020-06-24 ザ・ブロード・インスティテュート・インコーポレイテッド 組成物、及びヌクレオチドリピート障害におけるｃｒｉｓｐｒ−ｃａｓ系の使用方法
WO2015089427A1 (en) 2013-12-12 2015-06-18 The Broad Institute Inc. Crispr-cas systems and methods for altering expression of gene products, structural information and inducible modular cas enzymes
EP3083958B1 (en) 2013-12-19 2019-04-17 Amyris, Inc. Methods for genomic integration
WO2015105928A1 (en) 2014-01-08 2015-07-16 President And Fellows Of Harvard College Rna-guided gene drives
US10034463B2 (en) 2014-01-24 2018-07-31 Children's Medical Center Corporation High-throughput mouse model for optimizing antibody affinities
US10233456B2 (en) 2014-01-30 2019-03-19 The Board Of Trustees Of The University Of Arkansas Method, vectors, cells, seeds and kits for stacking genes into a single genomic site
US20150291969A1 (en) 2014-01-30 2015-10-15 Chromatin, Inc. Compositions for reduced lignin content in sorghum and improving cell wall digestibility, and methods of making the same
US11028388B2 (en) 2014-03-05 2021-06-08 Editas Medicine, Inc. CRISPR/Cas-related methods and compositions for treating Usher syndrome and retinitis pigmentosa
ES2745769T3 (es) 2014-03-10 2020-03-03 Editas Medicine Inc Procedimientos y composiciones relacionados con CRISPR/CAS para tratar la amaurosis congénita de Leber 10 (LCA10)
EP4659765A3 (en) 2014-03-12 2026-02-18 Precision Biosciences, Inc. Dystrophin gene exon deletion using engineered nucleases
KR102450868B1 (ko) 2014-03-14 2022-10-06 시버스 유에스 엘엘씨 올리고뉴클레오타이드 매개 유전자 보수를 사용한 표적화된 유전자 변형의 효율을 증가시키기 위한 방법 및 조성물
MX375361B (es) 2014-03-26 2025-03-06 Univ Maryland Edicion de genoma dirigida en cigotos de animales grandes domesticos.
GB201406968D0 (en) 2014-04-17 2014-06-04 Green Biologics Ltd Deletion mutants
US20170076039A1 (en) 2014-04-24 2017-03-16 Institute For Basic Science A Method of Selecting a Nuclease Target Sequence for Gene Knockout Based on Microhomology
GB201407852D0 (en) 2014-05-02 2014-06-18 Iontas Ltd Preparation of libraries od protein variants expressed in eukaryotic cells and use for selecting binding molecules
EP3142706A1 (en) 2014-05-16 2017-03-22 Vrije Universiteit Brussel Genetic correction of myotonic dystrophy type 1
WO2015184259A1 (en) 2014-05-30 2015-12-03 The Board Of Trustees Of The Leland Stanford Junior University Compositions and methods to treat latent viral infections
HRP20200529T1 (hr) 2014-06-06 2020-09-04 Regeneron Pharmaceuticals, Inc. Postupci i pripravci za modificiranje ciljnog lokusa
ES2788426T3 (es) 2014-06-16 2020-10-21 Univ Johns Hopkins Composiciones y métodos para la expresión de ARNs de guía de CRISPR utilizando el promotor de H1
SI3161128T1 (sl) 2014-06-26 2019-02-28 Regeneron Pharmaceuticals, Inc. Postopki in sestavki za ciljano genetsko spremembo in postopki uporabe
KR20170032406A (ko) 2014-07-15 2017-03-22 주노 쎄러퓨티크스 인코퍼레이티드 입양 세포 치료를 위한 조작된 세포
US9944933B2 (en) 2014-07-17 2018-04-17 Georgia Tech Research Corporation Aptamer-guided gene targeting
EP3193944B1 (en) 2014-07-17 2021-04-07 University of Pittsburgh - Of the Commonwealth System of Higher Education Methods of treating cells containing fusion genes
SG11201701245QA (en) 2014-08-27 2017-03-30 Caribou Biosciences Inc Methods for increasing cas9-mediated engineering efficiency
EP3188763B1 (en) 2014-09-02 2020-05-13 The Regents of The University of California Methods and compositions for rna-directed target dna modification
WO2016049163A2 (en) 2014-09-24 2016-03-31 The Broad Institute Inc. Use and production of chd8+/- transgenic animals with behavioral phenotypes characteristic of autism spectrum disorder
WO2016049024A2 (en) 2014-09-24 2016-03-31 The Broad Institute Inc. Delivery, use and therapeutic applications of the crispr-cas systems and compositions for modeling competition of multiple cancer mutations in vivo
WO2016049258A2 (en) 2014-09-25 2016-03-31 The Broad Institute Inc. Functional screening with optimized functional crispr-cas systems
JP2017534295A (ja) 2014-09-29 2017-11-24 ザ ジャクソン ラボラトリー エレクトロポレーションによる遺伝子改変哺乳動物の高効率ハイスループット生成
EP3201340B1 (en) 2014-10-01 2020-12-02 The General Hospital Corporation Methods for increasing efficiency of nuclease-induced homology-directed repair
AU2015330699B2 (en) 2014-10-10 2021-12-02 Editas Medicine, Inc. Compositions and methods for promoting homology directed repair
WO2016061073A1 (en) 2014-10-14 2016-04-21 Memorial Sloan-Kettering Cancer Center Composition and method for in vivo engineering of chromosomal rearrangements
BR112017007770A2 (pt) 2014-10-15 2018-01-16 Regeneron Pharma cultura in vitro, população de hipscs, método para modificar um locus-alvo genômico, e, hipsc.
CA2964796C (en) 2014-10-17 2022-01-11 The Penn State Research Foundation Methods and compositions for multiplex rna guided genome editing and other rna technologies
WO2016065364A1 (en) 2014-10-24 2016-04-28 Life Technologies Corporation Compositions and methods for enhancing homologous recombination
EP3215623A4 (en) 2014-11-06 2018-09-26 President and Fellows of Harvard College Cells lacking b2m surface expression and methods for allogeneic administration of such cells
EP4464338A3 (en) 2014-11-07 2025-02-12 Editas Medicine, Inc. Systems for improving crispr/cas-mediated genome-editing
KR102531016B1 (ko) 2014-11-21 2023-05-10 리제너론 파마슈티칼스 인코포레이티드 쌍 형성된 가이드 rna를 사용하는 표적화된 유전자 변형을 위한 방법 및 조성물
KR20170081268A (ko) 2014-11-27 2017-07-11 단지거 이노베이션즈 엘티디. 게놈 편집용 핵산 구조체
US20170266320A1 (en) 2014-12-01 2017-09-21 President And Fellows Of Harvard College RNA-Guided Systems for In Vivo Gene Editing
WO2016094880A1 (en) 2014-12-12 2016-06-16 The Broad Institute Inc. Delivery, use and therapeutic applications of crispr systems and compositions for genome editing as to hematopoietic stem cells (hscs)
WO2016094874A1 (en) 2014-12-12 2016-06-16 The Broad Institute Inc. Escorted and functionalized guides for crispr-cas systems
WO2016094872A1 (en) 2014-12-12 2016-06-16 The Broad Institute Inc. Dead guides for crispr transcription factors
WO2016097751A1 (en) 2014-12-18 2016-06-23 The University Of Bath Method of cas9 mediated genome engineering
ES2947714T3 (es) 2014-12-19 2023-08-17 Regeneron Pharma Métodos y composiciones para la modificación genética dirigida a través de múltiples direccionamientos en un solo paso
US10863730B2 (en) 2014-12-26 2020-12-15 Riken Gene knockout method
WO2016112242A1 (en) 2015-01-08 2016-07-14 President And Fellows Of Harvard College Split cas9 proteins
EP3242938B1 (en) 2015-01-09 2020-01-08 Bio-Rad Laboratories, Inc. Detection of genome editing
CN107429263A (zh) 2015-01-15 2017-12-01 斯坦福大学托管董事会 调控基因组编辑的方法
WO2016130697A1 (en) 2015-02-11 2016-08-18 Memorial Sloan Kettering Cancer Center Methods and kits for generating vectors that co-express multiple target molecules
GB2535532B (en) 2015-02-23 2021-05-12 Knorr Bremse Systeme Fuer Nutzfahrzeuge Gmbh Brake valve arrangement
BR112017017812A2 (en) 2015-02-23 2018-04-10 Crispr Therapeutics Ag Materials and methods for treatment of hemoglobinopathies
WO2016135559A2 (en) 2015-02-23 2016-09-01 Crispr Therapeutics Ag Materials and methods for treatment of human genetic diseases including hemoglobinopathies
EP3265560B1 (en) 2015-03-02 2021-12-08 Sinai Health System Homologous recombination factors
GB201504223D0 (en) 2015-03-12 2015-04-29 Genome Res Ltd Biallelic genetic modification
EP3274453B1 (en) 2015-03-26 2021-01-27 Editas Medicine, Inc. Crispr/cas-mediated gene conversion
AU2016243583B2 (en) 2015-03-27 2022-03-10 President And Fellows Of Harvard College Modified T cells and methods of making and using the same
EP3748004A1 (en) 2015-04-01 2020-12-09 Editas Medicine, Inc. Crispr/cas-related methods and compositions for treating duchenne muscular dystrophy and becker muscular dystrophy
US10155938B2 (en) 2015-04-14 2018-12-18 City Of Hope Coexpression of CAS9 and TREX2 for targeted mutagenesis
WO2016168890A1 (en) 2015-04-22 2016-10-27 Genea Ip Holdings Pty Ltd Generation of muscle-lineage cells from stem cells
WO2016174056A1 (en) 2015-04-27 2016-11-03 Genethon Compositions and methods for the treatment of nucleotide repeat expansion disorders
EP3289080B1 (en) 2015-04-30 2021-08-25 The Trustees of Columbia University in the City of New York Gene therapy for autosomal dominant diseases
BR112017024514A2 (pt) 2015-05-16 2018-07-24 Genzyme Corporation edição genética de mutações intrônicas profundas
US9790490B2 (en) 2015-06-18 2017-10-17 The Broad Institute Inc. CRISPR enzymes and systems
CN108513580A (zh) 2015-10-08 2018-09-07 哈佛学院董事及会员团体 多重基因组编辑
BR112018008134A2 (pt) 2015-10-20 2018-11-06 Pioneer Hi Bred Int método para restaurar a função de um produto gênico não funcional no genoma de uma célula, método para editar uma sequência nucleotídica no genoma de uma célula, planta ou planta de progênie, método para editar uma sequência nucleotídica no genoma de uma célula sem o uso de um molde polinucleotídico de modificação e método para entregar um complexo de rna guia/endonuclease cas numa célula
CN108471731A (zh) 2015-11-06 2018-08-31 杰克逊实验室 大型基因组dna敲入及其用途
US11597924B2 (en) 2016-03-25 2023-03-07 Editas Medicine, Inc. Genome editing systems comprising repair-modulating enzyme molecules and methods of their use
WO2017173004A1 (en) 2016-03-30 2017-10-05 Mikuni Takayasu A method for in vivo precise genome editing
US11773410B2 (en) 2016-04-13 2023-10-03 University Of Massachusetts Repairing compound heterozygous recessive mutations by allele exchange
CN113831407B (zh) 2016-05-20 2024-06-11 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
US11643670B2 (en) 2018-01-29 2023-05-09 Massachusetts Institute Of Technology Methods of enhancing chromosomal homologous recombination

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2014104878A1 (en) 2012-12-27 2014-07-03 Keygene N.V. Method for removing genetic linkage in a plant

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
BBRC.,445(4):791-794(2014.1.)
Nat Commun.,doi:10.1038/ncomms5240(2014.6.26.)
Nucleic Acids Res.,43(3):e21.doi: 10.1093/nar/gku1246(2014.11.20.)

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