ES2777217T3 - Suministro, modificación y optimización de sistemas de guía en tándem, métodos y composiciones para la manipulación de secuencias - Google Patents
Suministro, modificación y optimización de sistemas de guía en tándem, métodos y composiciones para la manipulación de secuencias Download PDFInfo
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| US201461979942P | 2014-04-15 | 2014-04-15 | |
| PCT/US2014/041800 WO2014204724A1 (en) | 2013-06-17 | 2014-06-10 | Delivery, engineering and optimization of tandem guide systems, methods and compositions for sequence manipulation |
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Families Citing this family (300)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP6261500B2 (ja) | 2011-07-22 | 2018-01-17 | プレジデント アンド フェローズ オブ ハーバード カレッジ | ヌクレアーゼ切断特異性の評価および改善 |
| MY189533A (en) | 2012-05-25 | 2022-02-16 | Univ California | Methods and compositions for rna-directed target dna modification and for rna-directed modulation of transcription |
| KR20230065381A (ko) * | 2012-07-25 | 2023-05-11 | 더 브로드 인스티튜트, 인코퍼레이티드 | 유도 ｄｎａ 결합 단백질 및 게놈 교란 도구 및 이의 적용 |
| WO2014065596A1 (en) | 2012-10-23 | 2014-05-01 | 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 |
| WO2014093709A1 (en) | 2012-12-12 | 2014-06-19 | The Broad Institute, Inc. | Methods, models, systems, and apparatus for identifying target sequences for cas enzymes or crispr-cas systems for target sequences and conveying results thereof |
| WO2014093701A1 (en) | 2012-12-12 | 2014-06-19 | The Broad Institute, Inc. | Functional genomics using crispr-cas systems, compositions, methods, knock out libraries and applications thereof |
| CA2894668A1 (en) | 2012-12-12 | 2014-06-19 | The Broad Institute, Inc. | Crispr-cas systems and methods for altering expression of gene products in eukaryotic cells |
| EP4299741A3 (en) | 2012-12-12 | 2024-02-28 | The Broad Institute, Inc. | Delivery, engineering and optimization of systems, methods and compositions for sequence manipulation and therapeutic applications |
| KR102210319B1 (ko) | 2013-03-15 | 2021-02-01 | 더 제너럴 하스피탈 코포레이션 | 특정 게놈 좌위에 대한 유전적 및 후성적 조절 단백질의 rna-안내 표적화 |
| 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 |
| RS62263B1 (sr) | 2013-04-16 | 2021-09-30 | Regeneron Pharma | Ciljana modifikacija genoma pacova |
| DK3011029T3 (da) | 2013-06-17 | 2020-03-16 | Broad Inst Inc | Administration, modificering og optimering af tandem-guidesystemer, fremgangsmåder og sammensætninger til sekvensmanipulering |
| WO2014204727A1 (en) | 2013-06-17 | 2014-12-24 | The Broad Institute Inc. | Functional genomics using crispr-cas systems, compositions methods, screens and applications thereof |
| KR20160056869A (ko) * | 2013-06-17 | 2016-05-20 | 더 브로드 인스티튜트, 인코퍼레이티드 | 바이러스 구성성분을 사용하여 장애 및 질환을 표적화하기 위한 crispr-cas 시스템 및 조성물의 전달, 용도 및 치료 적용 |
| EP3011031B1 (en) | 2013-06-17 | 2020-09-30 | The Broad Institute Inc. | Delivery and use of the crispr-cas systems, vectors and compositions for hepatic targeting and therapy |
| 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 |
| US20150044192A1 (en) | 2013-08-09 | 2015-02-12 | President And Fellows Of Harvard College | Methods for identifying a target site of a cas9 nuclease |
| US9359599B2 (en) | 2013-08-22 | 2016-06-07 | President And Fellows Of Harvard College | Engineered transcription activator-like effector (TALE) domains and uses thereof |
| US9322037B2 (en) | 2013-09-06 | 2016-04-26 | President And Fellows Of Harvard College | Cas9-FokI fusion proteins and uses thereof |
| US9737604B2 (en) | 2013-09-06 | 2017-08-22 | President And Fellows Of Harvard College | Use of cationic lipids to deliver CAS9 |
| US9228207B2 (en) | 2013-09-06 | 2016-01-05 | President And Fellows Of Harvard College | Switchable gRNAs comprising aptamers |
| WO2015040402A1 (en) | 2013-09-18 | 2015-03-26 | Kymab Limited | Methods. cells & organisms |
| WO2015065964A1 (en) | 2013-10-28 | 2015-05-07 | The Broad Institute Inc. | Functional genomics using crispr-cas systems, compositions, methods, screens and applications thereof |
| WO2015066119A1 (en) | 2013-10-30 | 2015-05-07 | North Carolina State University | Compositions and methods related to a type-ii crispr-cas system in lactobacillus buchneri |
| PT3066201T (pt) | 2013-11-07 | 2018-06-04 | Massachusetts Inst Technology | Métodos e composições relacionadas com crispr com arng reguladores |
| RU2725520C2 (ru) | 2013-12-11 | 2020-07-02 | Регенерон Фармасьютикалс, Инк. | Способы и композиции для направленной модификации генома |
| CA2932479A1 (en) | 2013-12-12 | 2015-06-18 | The Rockefeller University | Delivery, use and therapeutic applications of the crispr-cas systems and compositions for hbv and viral diseases and disorders |
| WO2015089364A1 (en) | 2013-12-12 | 2015-06-18 | The Broad Institute Inc. | Crystal structure of a crispr-cas system, and uses thereof |
| US9068179B1 (en) | 2013-12-12 | 2015-06-30 | President And Fellows Of Harvard College | Methods for correcting presenilin point mutations |
| WO2015089473A1 (en) | 2013-12-12 | 2015-06-18 | The Broad Institute Inc. | Engineering of systems, methods and optimized guide compositions with new architectures for sequence manipulation |
| 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 |
| CN106103705A (zh) | 2013-12-12 | 2016-11-09 | 布罗德研究所有限公司 | 核苷酸重复障碍中crispr‑cas系统的组合物和使用方法 |
| KR20250068794A (ko) | 2013-12-12 | 2025-05-16 | 더 브로드 인스티튜트, 인코퍼레이티드 | 게놈 편집을 위한 ｃｒｉｓｐｒ-ｃａｓ 시스템 및 조성물의 전달, 용도 및 치료적 응용 |
| US10787654B2 (en) | 2014-01-24 | 2020-09-29 | North Carolina State University | Methods and compositions for sequence guiding Cas9 targeting |
| EP3514246B1 (en) | 2014-02-27 | 2021-11-17 | The Broad Institute, Inc. | T cell balance gene expression and methods of use thereof |
| US11439712B2 (en) | 2014-04-08 | 2022-09-13 | North Carolina State University | Methods and compositions for RNA-directed repression of transcription using CRISPR-associated genes |
| US10077453B2 (en) | 2014-07-30 | 2018-09-18 | President And Fellows Of Harvard College | CAS9 proteins including ligand-dependent inteins |
| WO2016028682A1 (en) * | 2014-08-17 | 2016-02-25 | The Broad Institute Inc. | Genome editing using cas9 nickases |
| WO2016033298A1 (en) | 2014-08-28 | 2016-03-03 | North Carolina State University | Novel cas9 proteins and guiding features for dna targeting and genome editing |
| 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 |
| WO2016049251A1 (en) | 2014-09-24 | 2016-03-31 | The Broad Institute Inc. | Delivery, use and therapeutic applications of the crispr-cas systems and compositions for modeling mutations in leukocytes |
| WO2016049258A2 (en) | 2014-09-25 | 2016-03-31 | The Broad Institute Inc. | Functional screening with optimized functional crispr-cas systems |
| AU2015330699B2 (en) | 2014-10-10 | 2021-12-02 | Editas Medicine, Inc. | Compositions and methods for promoting homology directed repair |
| KR20170070136A (ko) | 2014-10-15 | 2017-06-21 | 리제너론 파마슈티칼스 인코포레이티드 | 만능성 세포를 생성하거나 유지하는 방법 및 조성물 |
| US20170247762A1 (en) | 2014-10-27 | 2017-08-31 | The Board Institute Inc. | Compositions, methods and use of synthetic lethal screening |
| US10725041B2 (en) * | 2014-11-04 | 2020-07-28 | Versiti Blood Research Institute Foundation, Inc. | Method to bioengineer designer platelets using gene editing and stem cell methodologies |
| AU2015342749B2 (en) | 2014-11-07 | 2022-01-27 | Editas Medicine, Inc. | Methods for improving CRISPR/Cas-mediated genome-editing |
| IL301900A (en) | 2014-11-21 | 2023-06-01 | Regeneron Pharma | Methods and compositions for targeted genetic modification using paired guide rnas |
| EP3626832B1 (en) | 2014-11-25 | 2024-06-12 | The Brigham and Women's Hospital, Inc. | Method of identifying a person having a predisposition to or afflicted with a cardiometabolic disease |
| EP4400584A3 (en) | 2014-12-03 | 2024-10-16 | Agilent Technologies, Inc. | Guide rna with chemical modifications |
| AU2015360502A1 (en) | 2014-12-10 | 2017-06-29 | Regents Of The University Of Minnesota | Genetically modified cells, tissues, and organs for treating disease |
| WO2016094867A1 (en) | 2014-12-12 | 2016-06-16 | The Broad Institute Inc. | Protected guide rnas (pgrnas) |
| WO2016094872A1 (en) | 2014-12-12 | 2016-06-16 | The Broad Institute Inc. | Dead guides for crispr transcription factors |
| WO2016094880A1 (en) | 2014-12-12 | 2016-06-16 | The Broad Institute Inc. | Delivery, use and therapeutic applications of crispr systems and compositions for genome editing as to hematopoietic stem cells (hscs) |
| WO2016094874A1 (en) | 2014-12-12 | 2016-06-16 | The Broad Institute Inc. | Escorted and functionalized guides for crispr-cas systems |
| WO2016100974A1 (en) | 2014-12-19 | 2016-06-23 | The Broad Institute Inc. | Unbiased identification of double-strand breaks and genomic rearrangement by genome-wide insert capture sequencing |
| WO2016106236A1 (en) | 2014-12-23 | 2016-06-30 | The Broad Institute Inc. | Rna-targeting system |
| WO2016106244A1 (en) | 2014-12-24 | 2016-06-30 | The Broad Institute Inc. | Crispr having or associated with destabilization domains |
| WO2016108926A1 (en) | 2014-12-30 | 2016-07-07 | The Broad Institute Inc. | Crispr mediated in vivo modeling and genetic screening of tumor growth and metastasis |
| CA2972454C (en) * | 2014-12-31 | 2024-09-10 | Viridos, Inc. | Compositions and methods for high efficiency in in vivo genome editing |
| KR102319192B1 (ko) | 2015-01-28 | 2021-10-28 | 카리부 바이오사이언시스 인코포레이티드 | Crispr 하이브리드 dna/rna 폴리뉴클레오티드 및 사용 방법 |
| WO2016130697A1 (en) * | 2015-02-11 | 2016-08-18 | Memorial Sloan Kettering Cancer Center | Methods and kits for generating vectors that co-express multiple target molecules |
| EP3262193A2 (en) | 2015-02-26 | 2018-01-03 | The Broad Institute Inc. | T cell balance gene expression, compositions of matters and methods of use thereof |
| US9944912B2 (en) | 2015-03-03 | 2018-04-17 | The General Hospital Corporation | Engineered CRISPR-Cas9 nucleases with altered PAM specificity |
| EP3280803B1 (en) | 2015-04-06 | 2021-05-26 | The Board of Trustees of the Leland Stanford Junior University | Chemically modified guide rnas for crispr/cas-mediated gene regulation |
| GB201506509D0 (en) | 2015-04-16 | 2015-06-03 | Univ Wageningen | Nuclease-mediated genome editing |
| WO2016182893A1 (en) | 2015-05-08 | 2016-11-17 | Teh Broad Institute Inc. | Functional genomics using crispr-cas systems for saturating mutagenesis of non-coding elements, compositions, methods, libraries and applications thereof |
| CA2986310A1 (en) | 2015-05-11 | 2016-11-17 | Editas Medicine, Inc. | Optimized crispr/cas9 systems and methods for gene editing in stem cells |
| CN107849547B (zh) | 2015-05-16 | 2022-04-19 | 建新公司 | 深内含子突变的基因编辑 |
| CN108026536A (zh) | 2015-05-29 | 2018-05-11 | 北卡罗来纳州立大学 | 使用crispr核酸筛选细菌、古细菌、藻类和酵母的方法 |
| WO2016196539A2 (en) | 2015-06-01 | 2016-12-08 | Temple University - Of The Commonwealth System Of Higher Education | Methods and compositions for rna-guided treatment of hiv infection |
| EP3307887A1 (en) | 2015-06-09 | 2018-04-18 | Editas Medicine, Inc. | Crispr/cas-related methods and compositions for improving transplantation |
| EP4299754A3 (en) | 2015-06-15 | 2024-03-20 | North Carolina State University | Methods and compositions for efficient delivery of nucleic acids and rna-based antimicrobials |
| WO2016205728A1 (en) | 2015-06-17 | 2016-12-22 | Massachusetts Institute Of Technology | Crispr mediated recording of cellular events |
| US9790490B2 (en) | 2015-06-18 | 2017-10-17 | The Broad Institute Inc. | CRISPR enzymes and systems |
| KR102840885B1 (ko) | 2015-06-18 | 2025-07-30 | 더 브로드 인스티튜트, 인코퍼레이티드 | 표적외 효과를 감소시키는 crispr 효소 돌연변이 |
| 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 |
| AU2016279062A1 (en) | 2015-06-18 | 2019-03-28 | Omar O. Abudayyeh | Novel CRISPR enzymes and systems |
| WO2016205745A2 (en) * | 2015-06-18 | 2016-12-22 | The Broad Institute Inc. | Cell sorting |
| FI3430134T3 (fi) | 2015-06-18 | 2023-01-13 | Uusia CRISPR-entsyymejä ja järjestelmiä | |
| US10648020B2 (en) | 2015-06-18 | 2020-05-12 | The Broad Institute, Inc. | CRISPR enzymes and systems |
| EP4545544A3 (en) | 2015-06-29 | 2025-10-08 | Ionis Pharmaceuticals, Inc. | Modified crispr rna and modified single crispr rna and uses thereof |
| WO2017023803A1 (en) | 2015-07-31 | 2017-02-09 | Regents Of The University Of Minnesota | Modified cells and methods of therapy |
| WO2017023974A1 (en) * | 2015-08-03 | 2017-02-09 | President And Fellows Of Harvard College | Cas9 genome editing and transcriptional regulation |
| EP3334484B1 (en) | 2015-08-12 | 2024-12-25 | The General Hospital Corporation | Compositions that promote hypoxia or the hypoxia response for the treatment and prevention of mitochondrial dysfunction |
| WO2017031370A1 (en) | 2015-08-18 | 2017-02-23 | The Broad Institute, Inc. | Methods and compositions for altering function and structure of chromatin loops and/or domains |
| US9926546B2 (en) | 2015-08-28 | 2018-03-27 | The General Hospital Corporation | Engineered CRISPR-Cas9 nucleases |
| US9512446B1 (en) | 2015-08-28 | 2016-12-06 | The General Hospital Corporation | Engineered CRISPR-Cas9 nucleases |
| ES2959815T3 (es) * | 2015-09-21 | 2024-02-28 | Arcturus Therapeutics Inc | Edición génica selectiva de alelo y usos de la misma |
| WO2017053879A1 (en) | 2015-09-24 | 2017-03-30 | 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 |
| WO2017069958A2 (en) | 2015-10-09 | 2017-04-27 | The Brigham And Women's Hospital, Inc. | Modulation of novel immune checkpoint targets |
| KR20250021623A (ko) | 2015-10-22 | 2025-02-13 | 더 브로드 인스티튜트, 인코퍼레이티드 | 타입 vi-b crispr 효소 및 시스템 |
| EP3365356B1 (en) | 2015-10-23 | 2023-06-28 | President and Fellows of Harvard College | Nucleobase editors and uses thereof |
| WO2017074788A1 (en) | 2015-10-27 | 2017-05-04 | The Broad Institute Inc. | Compositions and methods for targeting cancer-specific sequence variations |
| EP3368689B1 (en) | 2015-10-28 | 2020-06-17 | The Broad Institute, Inc. | Composition for modulating immune responses by use of immune cell gene signature |
| US11092607B2 (en) | 2015-10-28 | 2021-08-17 | The Board Institute, Inc. | Multiplex analysis of single cell constituents |
| WO2017075465A1 (en) | 2015-10-28 | 2017-05-04 | The Broad Institute Inc. | Compositions and methods for evaluating and modulating immune responses by detecting and targeting gata3 |
| WO2017075451A1 (en) | 2015-10-28 | 2017-05-04 | The Broad Institute Inc. | Compositions and methods for evaluating and modulating immune responses by detecting and targeting pou2af1 |
| WO2017075294A1 (en) | 2015-10-28 | 2017-05-04 | The Board Institute Inc. | Assays for massively combinatorial perturbation profiling and cellular circuit reconstruction |
| AU2016355178B9 (en) | 2015-11-19 | 2019-05-30 | Massachusetts Institute Of Technology | Lymphocyte antigen CD5-like (CD5L)-interleukin 12B (p40) heterodimers in immunity |
| US12110490B2 (en) | 2015-12-18 | 2024-10-08 | The Broad Institute, Inc. | CRISPR enzymes and systems |
| WO2017112620A1 (en) | 2015-12-22 | 2017-06-29 | North Carolina State University | Methods and compositions for delivery of crispr based antimicrobials |
| CN109072195A (zh) | 2015-12-30 | 2018-12-21 | 诺华股份有限公司 | 具有增强功效的免疫效应细胞疗法 |
| EP3408396A4 (en) * | 2016-01-26 | 2019-10-09 | Cedars-Sinai Medical Center | SYSTEMS AND METHODS OF DOUBLE RECOMBINASE-MEDIATED IN VIVO CASSETTE EXCHANGE (DRMCE) AND PATIENT MODELS THEREOF |
| EP3420102B1 (en) | 2016-02-22 | 2024-04-03 | Massachusetts Institute of Technology | Methods for identifying and modulating immune phenotypes |
| US11427861B2 (en) | 2016-03-17 | 2022-08-30 | Massachusetts Institute Of Technology | Methods for identifying and modulating co-occurant cellular phenotypes |
| EP3219799A1 (en) | 2016-03-17 | 2017-09-20 | IMBA-Institut für Molekulare Biotechnologie GmbH | Conditional crispr sgrna expression |
| EP3433363A1 (en) | 2016-03-25 | 2019-01-30 | Editas Medicine, Inc. | Genome editing systems comprising repair-modulating enzyme molecules and methods of their use |
| US11236313B2 (en) | 2016-04-13 | 2022-02-01 | Editas Medicine, Inc. | Cas9 fusion molecules, gene editing systems, and methods of use thereof |
| CA3026110A1 (en) * | 2016-04-19 | 2017-11-02 | The Broad Institute, Inc. | Novel crispr enzymes and systems |
| US12410416B2 (en) | 2016-04-19 | 2025-09-09 | The Broad Institute, Inc. | CRISPR enzymes and systems with modified pam specificity |
| EP3445853A1 (en) | 2016-04-19 | 2019-02-27 | The Broad Institute, Inc. | Cpf1 complexes with reduced indel activity |
| JP7324583B2 (ja) | 2016-05-20 | 2023-08-10 | 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 | 複数のガイドｒｎａを使用して免疫寛容を破綻させるための方法 |
| US10767175B2 (en) | 2016-06-08 | 2020-09-08 | Agilent Technologies, Inc. | High specificity genome editing using chemically modified guide RNAs |
| WO2017219027A1 (en) | 2016-06-17 | 2017-12-21 | The Broad Institute Inc. | Type vi crispr orthologs and systems |
| MA45670A (fr) | 2016-07-13 | 2019-05-22 | Vertex Pharma | Procédés, compositions et kits pour augmenter l'efficacité d'édition du génome |
| JP7026304B2 (ja) * | 2016-07-29 | 2022-02-28 | マックス－プランク－ゲゼルシャフト ツア フェルデルンク デア ヴィッセンシャフテン エー．ファウ． | 部位特異的ｄｎａ開裂及び修復による標的化原位置タンパク質多様化 |
| JP7231935B2 (ja) | 2016-08-03 | 2023-03-08 | プレジデント アンド フェローズ オブ ハーバード カレッジ | アデノシン核酸塩基編集因子およびそれらの使用 |
| EP3497214B1 (en) | 2016-08-09 | 2023-06-28 | President and Fellows of Harvard College | Programmable cas9-recombinase fusion proteins and uses thereof |
| CN110312799A (zh) | 2016-08-17 | 2019-10-08 | 博德研究所 | 新型crispr酶和系统 |
| US11630103B2 (en) | 2016-08-17 | 2023-04-18 | The Broad Institute, Inc. | Product and methods useful for modulating and evaluating immune responses |
| US12431216B2 (en) | 2016-08-17 | 2025-09-30 | Broad Institute, Inc. | Methods for identifying class 2 crispr-cas systems |
| EP4485466A3 (en) | 2016-08-17 | 2025-04-02 | The Broad Institute Inc. | Novel crispr enzymes and systems |
| EP3500677A4 (en) * | 2016-08-20 | 2020-04-01 | Avellino Lab USA, Inc. | Single guide rna, crispr/cas9 systems, and methods of use thereof |
| WO2018039438A1 (en) | 2016-08-24 | 2018-03-01 | President And Fellows Of Harvard College | Incorporation of unnatural amino acids into proteins using base editing |
| WO2018049025A2 (en) | 2016-09-07 | 2018-03-15 | The Broad Institute Inc. | Compositions and methods for evaluating and modulating immune responses |
| WO2018053053A1 (en) | 2016-09-13 | 2018-03-22 | The Broad Institute, Inc. | Proximity-dependent biotinylation and uses thereof |
| DK3516056T3 (da) * | 2016-09-23 | 2025-02-17 | Dsm Ip Assets Bv | Et guide-rna-ekspressionssystem til en værtscelle |
| US20190225974A1 (en) | 2016-09-23 | 2019-07-25 | BASF Agricultural Solutions Seed US LLC | Targeted genome optimization in plants |
| US12499971B2 (en) | 2016-09-28 | 2025-12-16 | The Broad Institute, Inc. | Systematic screening and mapping of regulatory elements in non-coding genomic regions, methods, compositions, and applications thereof |
| WO2018067991A1 (en) | 2016-10-07 | 2018-04-12 | The Brigham And Women's Hospital, Inc. | Modulation of novel immune checkpoint targets |
| EP3526320A1 (en) | 2016-10-14 | 2019-08-21 | President and Fellows of Harvard College | Aav delivery of nucleobase editors |
| CA3041068A1 (en) | 2016-10-18 | 2018-04-26 | Regents Of The University Of Minnesota | Tumor infiltrating lymphocytes and methods of therapy |
| EP3535396A1 (en) | 2016-11-01 | 2019-09-11 | Novartis AG | Methods and compositions for enhancing gene editing |
| WO2018089386A1 (en) | 2016-11-11 | 2018-05-17 | The Broad Institute, Inc. | Modulation of intestinal epithelial cell differentiation, maintenance and/or function through t cell action |
| US12331086B2 (en) * | 2016-11-14 | 2025-06-17 | Toolgen Incorporated | Artificially engineered SC function control system |
| US12404514B2 (en) | 2016-12-09 | 2025-09-02 | The Broad Institute, Inc. | CRISPR-systems for modifying a trait of interest in a plant |
| WO2018119010A1 (en) | 2016-12-19 | 2018-06-28 | Editas Medicine, Inc. | Assessing nuclease cleavage |
| US10745677B2 (en) | 2016-12-23 | 2020-08-18 | President And Fellows Of Harvard College | Editing of CCR5 receptor gene to protect against HIV infection |
| WO2018129486A2 (en) * | 2017-01-06 | 2018-07-12 | President And Fellows Of Harvard College | Composition and methods for enhanced knock-in reporter gene expression |
| 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 |
| TW201839136A (zh) | 2017-02-06 | 2018-11-01 | 瑞士商諾華公司 | 治療血色素異常症之組合物及方法 |
| KR20190116282A (ko) * | 2017-02-10 | 2019-10-14 | 지머젠 인코포레이티드 | 복수의 숙주를 위한 다중 dna 구조체의 조립 및 편집을 위한 모듈식 범용 플라스미드 디자인 전략 |
| GB201702847D0 (en) * | 2017-02-22 | 2017-04-05 | Cancer Res Tech Ltd | Cell labelling, tracking and retrieval |
| WO2018165504A1 (en) | 2017-03-09 | 2018-09-13 | President And Fellows Of Harvard College | Suppression of pain by gene editing |
| WO2018165631A1 (en) | 2017-03-09 | 2018-09-13 | President And Fellows Of Harvard College | Cancer vaccine |
| KR20190127797A (ko) | 2017-03-10 | 2019-11-13 | 프레지던트 앤드 펠로우즈 오브 하바드 칼리지 | 시토신에서 구아닌으로의 염기 편집제 |
| JP2020511141A (ja) | 2017-03-15 | 2020-04-16 | ザ・ブロード・インスティテュート・インコーポレイテッド | 新規Ｃａｓ１３ｂオルソログＣＲＩＳＰＲ酵素及び系 |
| WO2018170515A1 (en) | 2017-03-17 | 2018-09-20 | The Broad Institute, Inc. | Methods for identifying and modulating co-occurant cellular phenotypes |
| KR20240116572A (ko) | 2017-03-23 | 2024-07-29 | 프레지던트 앤드 펠로우즈 오브 하바드 칼리지 | 핵산 프로그램가능한 dna 결합 단백질을 포함하는 핵염기 편집제 |
| WO2018175924A1 (en) | 2017-03-24 | 2018-09-27 | The Broad Institute, Inc. | Methods and compositions for regulating innate lymphoid cell inflammatory responses |
| EP3601576A1 (en) | 2017-03-24 | 2020-02-05 | CureVac AG | Nucleic acids encoding crispr-associated proteins and uses thereof |
| WO2018183908A1 (en) | 2017-03-31 | 2018-10-04 | Dana-Farber Cancer Institute, Inc. | Compositions and methods for treating ovarian tumors |
| EP3606518A4 (en) | 2017-04-01 | 2021-04-07 | The Broad Institute, Inc. | METHODS AND COMPOSITIONS FOR DETECTION AND MODULATION OF IMMUNOTHERAPY RESISTANCE GENE SIGNATURE IN CANCER |
| KR20240155360A (ko) | 2017-04-12 | 2024-10-28 | 더 브로드 인스티튜트, 인코퍼레이티드 | 신규 타입 vi crispr 오르소로그 및 시스템 |
| EP3610266A4 (en) | 2017-04-12 | 2021-04-21 | Massachusetts Eye and Ear Infirmary | TUMOR SIGNATURE FOR METASTASIS, COMPOSITIONS OF MATERIAL AND THEIR METHODS OF USE |
| WO2018191520A1 (en) | 2017-04-12 | 2018-10-18 | The Broad Institute, Inc. | Respiratory and sweat gland ionocytes |
| WO2018191750A2 (en) | 2017-04-14 | 2018-10-18 | The Broad Institute Inc. | Novel delivery of large payloads |
| WO2018195019A1 (en) | 2017-04-18 | 2018-10-25 | The Broad Institute Inc. | Compositions for detecting secretion and methods of use |
| WO2018195486A1 (en) | 2017-04-21 | 2018-10-25 | The Broad Institute, Inc. | Targeted delivery to beta cells |
| WO2018201086A1 (en) | 2017-04-28 | 2018-11-01 | Editas Medicine, Inc. | Methods and systems for analyzing guide rna molecules |
| US11591601B2 (en) | 2017-05-05 | 2023-02-28 | The Broad Institute, Inc. | Methods for identification and modification of lncRNA associated with target genotypes and phenotypes |
| US12226479B2 (en) | 2017-05-11 | 2025-02-18 | The General Hospital Corporation | Methods and compositions of use of CD8+ tumor infiltrating lymphocyte subtypes and gene signatures thereof |
| US11560566B2 (en) | 2017-05-12 | 2023-01-24 | President And Fellows Of Harvard College | Aptazyme-embedded guide RNAs for use with CRISPR-Cas9 in genome editing and transcriptional activation |
| US11866697B2 (en) | 2017-05-18 | 2024-01-09 | The Broad Institute, Inc. | Systems, methods, and compositions for targeted nucleic acid editing |
| EP3625342B1 (en) | 2017-05-18 | 2022-08-24 | The Broad Institute, Inc. | Systems, methods, and compositions for targeted nucleic acid editing |
| WO2018217981A1 (en) | 2017-05-26 | 2018-11-29 | North Carolina State University | Altered guide rnas for modulating cas9 activity and methods of use |
| CA3102054A1 (en) | 2017-06-05 | 2018-12-13 | Fred Hutchinson Cancer Research Center | Genomic safe harbors for genetic therapies in human stem cells and engineered nanoparticles to provide targeted genetic therapies |
| 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. |
| WO2018232195A1 (en) | 2017-06-14 | 2018-12-20 | The Broad Institute, Inc. | Compositions and methods targeting complement component 3 for inhibiting tumor growth |
| EP3645054A4 (en) | 2017-06-26 | 2021-03-31 | The Broad Institute, Inc. | CRISPR / CAS-ADENINE DESAMINASE COMPOSITIONS, TARGETED NUCLEIC ACID EDITING SYSTEMS AND METHODS |
| WO2019003193A1 (en) | 2017-06-30 | 2019-01-03 | Novartis Ag | METHODS FOR TREATING DISEASES USING GENE EDITING SYSTEMS |
| JP2020530307A (ja) | 2017-06-30 | 2020-10-22 | インティマ・バイオサイエンス，インコーポレーテッド | 遺伝子治療のためのアデノ随伴ウイルスベクター |
| WO2019014390A1 (en) * | 2017-07-12 | 2019-01-17 | Refuge Biotechnologies, Inc. | METHODS AND SYSTEMS FOR CONDITIONAL REGULATION OF GENE EXPRESSION |
| WO2019014581A1 (en) | 2017-07-14 | 2019-01-17 | The Broad Institute, Inc. | METHODS AND COMPOSITIONS FOR MODULATING THE ACTIVITY OF A CYTOTOXIC LYMPHOCYTE |
| 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 |
| US12105089B2 (en) | 2017-07-17 | 2024-10-01 | The Broad Institute, Inc. | Cell atlas of the healthy and ulcerative colitis human colon |
| WO2019018694A1 (en) | 2017-07-19 | 2019-01-24 | Dana-Farber Cancer Institute, Inc. | DIAGNOSIS AND TREATMENT OF CANCER |
| WO2019023680A1 (en) | 2017-07-28 | 2019-01-31 | President And Fellows Of Harvard College | METHODS AND COMPOSITIONS FOR EVOLUTION OF BASIC EDITORS USING PHAGE-ASSISTED CONTINUOUS EVOLUTION (PACE) |
| EP3663310A4 (en) | 2017-08-04 | 2021-08-11 | Peking University | TALE RVD SPECIFICALLY RECOGNIZING A DNA BASE MODIFIED BY METHYLATION AND CORRESPONDING APPLICATION |
| WO2019028686A1 (zh) | 2017-08-08 | 2019-02-14 | 北京大学 | 基因敲除方法 |
| CA3073448A1 (en) | 2017-08-23 | 2019-02-28 | The General Hospital Corporation | Engineered crispr-cas9 nucleases with altered pam specificity |
| EP3676376B1 (en) | 2017-08-30 | 2025-01-15 | President and Fellows of Harvard College | High efficiency base editors comprising gam |
| CA3073848A1 (en) | 2017-09-21 | 2019-03-28 | The Broad Institute, Inc. | Systems, methods, and compositions for targeted nucleic acid editing |
| WO2019070755A1 (en) | 2017-10-02 | 2019-04-11 | The Broad Institute, Inc. | METHODS AND COMPOSITIONS FOR DETECTING AND MODULATING A GENETIC SIGNATURE OF IMMUNOTHERAPY RESISTANCE IN CANCER |
| EP3692152B1 (en) | 2017-10-04 | 2025-09-03 | The Broad Institute, Inc. | Methods and compositions for altering function and structure of chromatin loops and/or domains |
| CN111757937A (zh) | 2017-10-16 | 2020-10-09 | 布罗德研究所股份有限公司 | 腺苷碱基编辑器的用途 |
| WO2019079362A1 (en) | 2017-10-16 | 2019-04-25 | Massachusetts Institute Of Technology | HOST-PATHOGENIC INTERACTION OF MYCOBACTERIUM TUBERCULOSIS |
| IL274082B1 (en) | 2017-10-20 | 2025-09-01 | Hutchinson Fred Cancer Res | Systems and methods for producing genetically engineered B cells for expression of selected antibodies |
| US12227742B2 (en) | 2017-10-23 | 2025-02-18 | The Broad Institute, Inc. | Nucleic acid modifiers |
| WO2019089803A1 (en) | 2017-10-31 | 2019-05-09 | The Broad Institute, Inc. | Methods and compositions for studying cell evolution |
| US20210180053A1 (en) | 2017-11-01 | 2021-06-17 | Novartis Ag | Synthetic rnas and methods of use |
| WO2019094955A1 (en) | 2017-11-13 | 2019-05-16 | The Broad Institute, Inc. | Methods and compositions for targeting developmental and oncogenic programs in h3k27m gliomas |
| WO2019094984A1 (en) | 2017-11-13 | 2019-05-16 | The Broad Institute, Inc. | Methods for determining spatial and temporal gene expression dynamics during adult neurogenesis in single cells |
| MA50877A (fr) | 2017-11-21 | 2020-09-30 | Bayer Healthcare Llc | Matériaux et méthodes pour le traitement de la rétinite pigmentaire autosomique dominante |
| WO2019113506A1 (en) | 2017-12-07 | 2019-06-13 | The Broad Institute, Inc. | Methods and compositions for multiplexing single cell and single nuclei sequencing |
| WO2019118949A1 (en) | 2017-12-15 | 2019-06-20 | The Broad Institute, Inc. | Systems and methods for predicting repair outcomes in genetic engineering |
| US11994512B2 (en) | 2018-01-04 | 2024-05-28 | Massachusetts Institute Of Technology | Single-cell genomic methods to generate ex vivo cell systems that recapitulate in vivo biology with improved fidelity |
| 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 |
| KR20200110687A (ko) | 2018-01-17 | 2020-09-24 | 버텍스 파마슈티칼스 인코포레이티드 | 유전체 편집 효율을 증가시키기 위한 퀴녹살리논 화합물, 조성물, 방법 및 키트 |
| ES2980444T3 (es) | 2018-01-17 | 2024-10-01 | Vertex Pharma | Inhibidores de ADN-PK |
| US12258571B2 (en) | 2018-03-16 | 2025-03-25 | Cedars-Sinai Medical Center | Methods and compositions for inducible expression of neurotrophic factors |
| CN108424934A (zh) * | 2018-04-16 | 2018-08-21 | 和元生物技术（上海）股份有限公司 | 一种慢病毒cag-cmv双启动子改造载体构建及应用 |
| WO2019204585A1 (en) | 2018-04-19 | 2019-10-24 | Massachusetts Institute Of Technology | Single-stranded break detection in double-stranded dna |
| SI3560330T1 (sl) | 2018-04-24 | 2022-08-31 | KWS SAAT SE & Co. KGaA | Rastline z izboljšano prebavljivostjo in markerskimi haplotipi |
| US11957695B2 (en) | 2018-04-26 | 2024-04-16 | The Broad Institute, Inc. | Methods and compositions targeting glucocorticoid signaling for modulating immune responses |
| US12281301B2 (en) | 2018-04-27 | 2025-04-22 | The Broad Institute, Inc. | Sequencing-based proteomics |
| US20210386829A1 (en) | 2018-05-04 | 2021-12-16 | The Broad Institute, Inc. | Compositions and methods for modulating cgrp signaling to regulate innate lymphoid cell inflammatory responses |
| US12157760B2 (en) | 2018-05-23 | 2024-12-03 | The Broad Institute, Inc. | Base editors and uses thereof |
| US20210371932A1 (en) | 2018-06-01 | 2021-12-02 | Massachusetts Institute Of Technology | Methods and compositions for detecting and modulating microenvironment gene signatures from the csf of metastasis patients |
| CN108846258B (zh) * | 2018-06-08 | 2021-05-18 | 中国人民解放军军事科学院军事医学研究院 | 一种自动检测分节段rna病毒重配的方法 |
| EP3578658A1 (en) | 2018-06-08 | 2019-12-11 | Johann Wolfgang Goethe-Universität Frankfurt | Method for generating a gene editing vector with fixed guide rna pairs |
| US12036240B2 (en) | 2018-06-14 | 2024-07-16 | The Broad Institute, Inc. | Compositions and methods targeting complement component 3 for inhibiting tumor growth |
| WO2019237399A1 (zh) * | 2018-06-16 | 2019-12-19 | 深圳市博奥康生物科技有限公司 | CRISPR-Cas9特异性敲除人C2orf40基因的方法及其特异的sgRNA |
| US20210269866A1 (en) | 2018-06-26 | 2021-09-02 | The Broad Institute, Inc. | Crispr effector system based amplification methods, systems, and diagnostics |
| CA3101066A1 (en) | 2018-06-26 | 2020-01-02 | The Broad Institute, Inc. | Crispr/cas and transposase based amplification compositions, systems and methods |
| CA3104856A1 (en) | 2018-06-29 | 2020-01-02 | Editas Medicine, Inc. | Synthetic guide molecules, compositions and methods relating thereto |
| AU2019314433A1 (en) | 2018-07-31 | 2021-03-25 | Massachusetts Institute Of Technology | Novel CRISPR enzymes and systems |
| WO2020033601A1 (en) | 2018-08-07 | 2020-02-13 | The Broad Institute, Inc. | Novel cas12b enzymes and systems |
| WO2020041380A1 (en) | 2018-08-20 | 2020-02-27 | The Broad Institute, Inc. | Methods and compositions for optochemical control of crispr-cas9 |
| WO2020041387A1 (en) | 2018-08-20 | 2020-02-27 | The Brigham And Women's Hospital, Inc. | Degradation domain modifications for spatio-temporal control of rna-guided nucleases |
| EP3847650A1 (en) | 2018-09-06 | 2021-07-14 | The Broad Institute, Inc. | Nucleic acid assemblies for use in targeted delivery |
| EP3849565A4 (en) | 2018-09-12 | 2022-12-28 | Fred Hutchinson Cancer Research Center | REDUCTION OF CD33 EXPRESSION TO SELECTIVELY PROTECT THERAPEUTIC CELLS |
| KR20210070305A (ko) | 2018-09-18 | 2021-06-14 | 브이엔브이 뉴코 인크. | Arc 기반 캡시드 및 이의 용도 |
| WO2020072253A1 (en) | 2018-10-01 | 2020-04-09 | North Carolina State University | Recombinant type i crispr-cas system and uses thereof for screening for variant cells |
| WO2020072254A1 (en) | 2018-10-01 | 2020-04-09 | North Carolina State University | Recombinant type i crispr-cas system and uses thereof for killing target cells |
| US12264313B2 (en) | 2018-10-01 | 2025-04-01 | North Carolina State University | Recombinant type I CRISPR-Cas system and uses thereof for genome modification and alteration of expression |
| US10711267B2 (en) | 2018-10-01 | 2020-07-14 | North Carolina State University | Recombinant type I CRISPR-Cas system |
| WO2020077236A1 (en) | 2018-10-12 | 2020-04-16 | The Broad Institute, Inc. | Method for extracting nuclei or whole cells from formalin-fixed paraffin-embedded tissues |
| US20210379057A1 (en) | 2018-10-16 | 2021-12-09 | Massachusetts Institute Of Technology | Nutlin-3a for use in treating a mycobacterium tuberculosis infection |
| US12281338B2 (en) | 2018-10-29 | 2025-04-22 | The Broad Institute, Inc. | Nucleobase editors comprising GeoCas9 and uses thereof |
| WO2020097360A1 (en) * | 2018-11-07 | 2020-05-14 | The Regents Of The University Of Colorado, A Body Corporate | Methods and compositions for genome-wide analysis and use of genome cutting and repair |
| US12165743B2 (en) | 2018-11-09 | 2024-12-10 | The Broad Institute, Inc. | Compressed sensing for screening and tissue imaging |
| US20220062394A1 (en) | 2018-12-17 | 2022-03-03 | The Broad Institute, Inc. | Methods for identifying neoantigens |
| WO2020131862A1 (en) | 2018-12-17 | 2020-06-25 | The Broad Institute, Inc. | Crispr-associated transposase systems and methods of use thereof |
| KR20210106527A (ko) * | 2018-12-20 | 2021-08-30 | 페킹 유니버시티 | 바코드화 가이드 rna 구축물을 사용한 고효율의 유전자 스크리닝을 위한 조성물 및 방법 |
| CN111349654B (zh) * | 2018-12-20 | 2023-01-24 | 北京大学 | 使用加标签的向导rna构建体进行高效基因筛选的组合物和方法 |
| US11739156B2 (en) | 2019-01-06 | 2023-08-29 | The Broad Institute, Inc. Massachusetts Institute of Technology | Methods and compositions for overcoming immunosuppression |
| WO2020154500A1 (en) | 2019-01-23 | 2020-07-30 | The Broad Institute, Inc. | Supernegatively charged proteins and uses thereof |
| MX2021011426A (es) | 2019-03-19 | 2022-03-11 | Broad Inst Inc | Metodos y composiciones para editar secuencias de nucleótidos. |
| WO2020206036A1 (en) | 2019-04-01 | 2020-10-08 | The Broad Institute, Inc. | Novel nucleic acid modifier |
| CN111812066B (zh) * | 2019-04-10 | 2023-04-28 | 华东理工大学 | 基于CRISPR/Cas12a系统的生物传感器、试剂盒及其在小分子检测中的用途 |
| EP3956349A1 (en) | 2019-04-17 | 2022-02-23 | The Broad Institute, Inc. | Adenine base editors with reduced off-target effects |
| CN114096684B (zh) | 2019-05-13 | 2024-11-19 | 科沃施种子欧洲股份两合公司 | 玉米的耐旱性 |
| US20220235340A1 (en) | 2019-05-20 | 2022-07-28 | The Broad Institute, Inc. | Novel crispr-cas systems and uses thereof |
| US20220220469A1 (en) | 2019-05-20 | 2022-07-14 | The Broad Institute, Inc. | Non-class i multi-component nucleic acid targeting systems |
| AR118995A1 (es) | 2019-05-25 | 2021-11-17 | Kws Saat Se & Co Kgaa | Mejorador de la inducción de haploides |
| US20220243178A1 (en) | 2019-05-31 | 2022-08-04 | The Broad Institute, Inc. | Methods for treating metabolic disorders by targeting adcy5 |
| CN114729383A (zh) | 2019-07-02 | 2022-07-08 | 弗莱德哈钦森癌症研究中心 | 重组ad35载体及相关基因疗法改进 |
| CN112168808B (zh) * | 2019-07-02 | 2023-01-24 | 深圳市第二人民医院 | 一种基于crispr的细胞核靶向药物递送系统 |
| JPWO2021020550A1 (OSRAM) * | 2019-08-01 | 2021-02-04 | ||
| EP3772542A1 (en) | 2019-08-07 | 2021-02-10 | KWS SAAT SE & Co. KGaA | Modifying genetic variation in crops by modulating the pachytene checkpoint protein 2 |
| WO2021041922A1 (en) | 2019-08-30 | 2021-03-04 | The Broad Institute, Inc. | Crispr-associated mu transposase systems |
| EP4031660A1 (en) | 2019-09-20 | 2022-07-27 | The Broad Institute, Inc. | Novel type vi crispr enzymes and systems |
| CA3151690A1 (en) * | 2019-09-23 | 2021-04-01 | Beau WEBBER | Genetically-edited immune cells and methods of therapy |
| US11981922B2 (en) | 2019-10-03 | 2024-05-14 | Dana-Farber Cancer Institute, Inc. | Methods and compositions for the modulation of cell interactions and signaling in the tumor microenvironment |
| US12435330B2 (en) | 2019-10-10 | 2025-10-07 | The Broad Institute, Inc. | Methods and compositions for prime editing RNA |
| EP4045522A1 (en) | 2019-10-17 | 2022-08-24 | KWS SAAT SE & Co. KGaA | Enhanced disease resistance of crops by downregulation of repressor genes |
| IL293569A (en) * | 2019-12-11 | 2022-08-01 | Intellia Therapeutics Inc | Modified guide rnas for gene editing |
| WO2021151085A2 (en) | 2020-01-24 | 2021-07-29 | The General Hospital Corporation | Crispr-cas enzymes with enhanced on-target activity |
| EP4093864A4 (en) | 2020-01-24 | 2024-04-10 | The General Hospital Corporation | Unconstrained genome targeting with near-pamless engineered crispr-cas9 variants |
| EP3872190A1 (en) | 2020-02-26 | 2021-09-01 | Antibodies-Online GmbH | A method of using cut&run or cut&tag to validate crispr-cas targeting |
| MX2022014008A (es) | 2020-05-08 | 2023-02-09 | Broad Inst Inc | Métodos y composiciones para la edición simultánea de ambas cadenas de una secuencia de nucleótidos de doble cadena objetivo. |
| BR112022023443A2 (pt) | 2020-05-29 | 2022-12-20 | Kws Saat Se & Co Kgaa | Indução de haploides em plantas |
| WO2021252955A1 (en) * | 2020-06-12 | 2021-12-16 | Flagship Pioneering Innovations V, Inc. | Tandem anellovirus constructs |
| CN111979266A (zh) * | 2020-08-28 | 2020-11-24 | 江苏集萃药康生物科技有限公司 | 一种pcsk9人源化小鼠模型的构建方法及其应用 |
| WO2022087269A1 (en) * | 2020-10-21 | 2022-04-28 | Verint Americas Inc. | System and method of automated determination of use of sensitive information and corrective action for improper use |
| EP4001429A1 (en) | 2020-11-16 | 2022-05-25 | Antibodies-Online GmbH | Analysis of crispr-cas binding and cleavage sites followed by high-throughput sequencing (abc-seq) |
| CN114606196A (zh) * | 2020-12-04 | 2022-06-10 | 南京大学 | 一种进行siRNA表达和体内递送的细胞疗法 |
| CN112899306B (zh) * | 2020-12-21 | 2023-06-30 | 南京启真基因工程有限公司 | Crispr系统及其在构建gabrg2基因突变的克隆猪核供体细胞中的应用 |
| EP4288541A1 (en) | 2021-02-05 | 2023-12-13 | Christiana Care Gene Editing Institute, Inc. | Methods of and compositions for reducing gene expression and/or activity |
| US20230167487A2 (en) | 2021-07-12 | 2023-06-01 | Labsimply, Inc. | Crispr cascade assay |
| CN118368974A (zh) | 2021-07-30 | 2024-07-19 | 科沃施种子欧洲股份两合公司 | 具有提高的消化率和标记单倍型的植物 |
| EP4384616A4 (en) * | 2021-08-11 | 2025-08-27 | Univ Leland Stanford Junior | HIGH-THROUGHPUT PRECISION GENOME EDITING IN HUMAN CELLS |
| KR20240055811A (ko) | 2021-09-10 | 2024-04-29 | 애질런트 테크놀로지스, 인크. | 프라임 편집을 위한 화학적 변형을 갖는 가이드 rna |
| CA3237300A1 (en) | 2021-11-01 | 2023-05-04 | Tome Biosciences, Inc. | Single construct platform for simultaneous delivery of gene editing machinery and nucleic acid cargo |
| US20240408236A1 (en) | 2021-11-26 | 2024-12-12 | Epigenic Therapeutics, Inc. | Method of modulating pcsk9 and uses thereof |
| US11820983B2 (en) | 2021-12-13 | 2023-11-21 | Labsimply, Inc. | Tuning cascade assay kinetics via molecular design |
| US20230279375A1 (en) | 2021-12-13 | 2023-09-07 | Labsimply, Inc. | Signal boost cascade assay |
| WO2023122764A1 (en) | 2021-12-22 | 2023-06-29 | Tome Biosciences, Inc. | Co-delivery of a gene editor construct and a donor template |
| WO2023205744A1 (en) | 2022-04-20 | 2023-10-26 | Tome Biosciences, Inc. | Programmable gene insertion compositions |
| WO2023215831A1 (en) | 2022-05-04 | 2023-11-09 | Tome Biosciences, Inc. | Guide rna compositions for programmable gene insertion |
| WO2023225670A2 (en) | 2022-05-20 | 2023-11-23 | Tome Biosciences, Inc. | Ex vivo programmable gene insertion |
| WO2024020352A1 (en) * | 2022-07-18 | 2024-01-25 | Vertex Pharmaceuticals Incorporated | Tandem guide rnas (tg-rnas) and their use in genome editing |
| WO2024020587A2 (en) | 2022-07-22 | 2024-01-25 | Tome Biosciences, Inc. | Pleiopluripotent stem cell programmable gene insertion |
| EP4577660A1 (en) | 2022-08-26 | 2025-07-02 | KWS SAAT SE & Co. KGaA | Use of paired genes in hybrid breeding |
| US12091689B2 (en) * | 2022-09-30 | 2024-09-17 | Vedabio, Inc. | Delivery of therapeutics in vivo via a CRISPR-based cascade system |
| WO2024081156A1 (en) | 2022-10-14 | 2024-04-18 | Vedabio, Inc. | Detection of nucleic acid and non-nucleic acid target molecules |
| WO2024138194A1 (en) | 2022-12-22 | 2024-06-27 | Tome Biosciences, Inc. | Platforms, compositions, and methods for in vivo programmable gene insertion |
| WO2024253707A2 (en) | 2023-01-07 | 2024-12-12 | Vedabio, Inc. | Engineered nucleic acid-guided nucleases |
| US12060602B2 (en) | 2023-01-10 | 2024-08-13 | Vedabio, Inc. | Sample splitting for multiplexed detection of nucleic acids without amplification |
| US20240352485A1 (en) | 2023-04-19 | 2024-10-24 | Flagship Pioneering Innovations Vii, Llc | Compositions and methods for the production of libraries |
| WO2024234006A1 (en) | 2023-05-11 | 2024-11-14 | Tome Biosciences, Inc. | Systems, compositions, and methods for targeting liver sinusodial endothelial cells (lsecs) |
| WO2024236547A1 (en) | 2023-05-18 | 2024-11-21 | Inceptor Bio, Llc | Modified phagocytic cells expressing chimeric antigen receptors comprising a herpes virus entry mediator (hvem) co-stimulatory domain and uses thereof |
| WO2025006419A1 (en) | 2023-06-26 | 2025-01-02 | Flagship Pioneering Innovations Vii, Llc | Engineered plasmodia and related methods |
| WO2025046513A1 (en) | 2023-08-29 | 2025-03-06 | Inceptor Bio, Llc | Methods of manufacturing myeloid-derived cells from hematopoietic stem cells and compositions and uses thereof |
| WO2025050069A1 (en) | 2023-09-01 | 2025-03-06 | Tome Biosciences, Inc. | Programmable gene insertion using engineered integration enzymes |
| WO2025224107A1 (en) | 2024-04-22 | 2025-10-30 | Basecamp Research Ltd | Method and compositions for detecting off-target editing |
| WO2025224182A2 (en) | 2024-04-23 | 2025-10-30 | Basecamp Research Ltd | Single construct platform for simultaneous delivery of gene editing machinery and nucleic acid cargo |
Family Cites Families (165)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4217344A (en) | 1976-06-23 | 1980-08-12 | L'oreal | Compositions containing aqueous dispersions of lipid spheres |
| US4235871A (en) | 1978-02-24 | 1980-11-25 | Papahadjopoulos Demetrios P | Method of encapsulating biologically active materials in lipid vesicles |
| US4186183A (en) | 1978-03-29 | 1980-01-29 | The United States Of America As Represented By The Secretary Of The Army | Liposome carriers in chemotherapy of leishmaniasis |
| US4261975A (en) | 1979-09-19 | 1981-04-14 | Merck & Co., Inc. | Viral liposome particle |
| US4485054A (en) | 1982-10-04 | 1984-11-27 | Lipoderm Pharmaceuticals Limited | Method of encapsulating biologically active materials in multilamellar lipid vesicles (MLV) |
| US4501728A (en) | 1983-01-06 | 1985-02-26 | Technology Unlimited, Inc. | Masking of liposomes from RES recognition |
| US4946787A (en) | 1985-01-07 | 1990-08-07 | Syntex (U.S.A.) Inc. | N-(ω,(ω-1)-dialkyloxy)- and N-(ω,(ω-1)-dialkenyloxy)-alk-1-yl-N,N,N-tetrasubstituted ammonium lipids and uses therefor |
| US4897355A (en) | 1985-01-07 | 1990-01-30 | Syntex (U.S.A.) Inc. | N[ω,(ω-1)-dialkyloxy]- and N-[ω,(ω-1)-dialkenyloxy]-alk-1-yl-N,N,N-tetrasubstituted ammonium lipids and uses therefor |
| US5049386A (en) | 1985-01-07 | 1991-09-17 | Syntex (U.S.A.) Inc. | N-ω,(ω-1)-dialkyloxy)- and N-(ω,(ω-1)-dialkenyloxy)Alk-1-YL-N,N,N-tetrasubstituted ammonium lipids and uses therefor |
| US4797368A (en) | 1985-03-15 | 1989-01-10 | The United States Of America As Represented By The Department Of Health And Human Services | Adeno-associated virus as eukaryotic expression vector |
| US4774085A (en) | 1985-07-09 | 1988-09-27 | 501 Board of Regents, Univ. of Texas | Pharmaceutical administration systems containing a mixture of immunomodulators |
| EP0264166B1 (en) | 1986-04-09 | 1996-08-21 | Genzyme Corporation | Transgenic animals secreting desired proteins into milk |
| US4837028A (en) | 1986-12-24 | 1989-06-06 | Liposome Technology, Inc. | Liposomes with enhanced circulation time |
| US4873316A (en) | 1987-06-23 | 1989-10-10 | Biogen, Inc. | Isolation of exogenous recombinant proteins from the milk of transgenic mammals |
| US5143854A (en) | 1989-06-07 | 1992-09-01 | Affymax Technologies N.V. | Large scale photolithographic solid phase synthesis of polypeptides and receptor binding screening thereof |
| US5264618A (en) | 1990-04-19 | 1993-11-23 | Vical, Inc. | Cationic lipids for intracellular delivery of biologically active molecules |
| WO1991017424A1 (en) | 1990-05-03 | 1991-11-14 | Vical, Inc. | Intracellular delivery of biologically active substances by means of self-assembling lipid complexes |
| US5210015A (en) | 1990-08-06 | 1993-05-11 | Hoffman-La Roche Inc. | Homogeneous assay system using the nuclease activity of a nucleic acid polymerase |
| US5173414A (en) | 1990-10-30 | 1992-12-22 | Applied Immune Sciences, Inc. | Production of recombinant adeno-associated virus vectors |
| US7150982B2 (en) | 1991-09-09 | 2006-12-19 | Third Wave Technologies, Inc. | RNA detection assays |
| US5587308A (en) | 1992-06-02 | 1996-12-24 | The United States Of America As Represented By The Department Of Health & Human Services | Modified adeno-associated virus vector capable of expression from a novel promoter |
| US7745416B2 (en) | 1995-04-11 | 2010-06-29 | The Regents Of The University Of California | Method for in vivo regulation of cardiac muscle contractility |
| JPH10510433A (ja) | 1995-06-06 | 1998-10-13 | アイシス・ファーマシューティカルス・インコーポレーテッド | 高いキラル純度のホスホロチオエート結合を有するオリゴヌクレオチド |
| US5985662A (en) | 1995-07-13 | 1999-11-16 | Isis Pharmaceuticals Inc. | Antisense inhibition of hepatitis B virus replication |
| US5622856A (en) | 1995-08-03 | 1997-04-22 | Avigen | High efficiency helper system for AAV vector production |
| US5846946A (en) | 1996-06-14 | 1998-12-08 | Pasteur Merieux Serums Et Vaccins | Compositions and methods for administering Borrelia DNA |
| US6251677B1 (en) | 1997-08-25 | 2001-06-26 | The Trustees Of The University Of Pennsylvania | Hybrid adenovirus-AAV virus and methods of use thereof |
| EP1025217B1 (en) | 1997-10-24 | 2006-10-04 | Invitrogen Corporation | Recombinational cloning using nucleic acids having recombination sites |
| US6750059B1 (en) | 1998-07-16 | 2004-06-15 | Whatman, Inc. | Archiving of vectors |
| US6534261B1 (en) | 1999-01-12 | 2003-03-18 | Sangamo Biosciences, Inc. | Regulation of endogenous gene expression in cells using zinc finger proteins |
| US7868149B2 (en) | 1999-07-20 | 2011-01-11 | Monsanto Technology Llc | Plant genome sequence and uses thereof |
| US6603061B1 (en) | 1999-07-29 | 2003-08-05 | Monsanto Company | Agrobacterium-mediated plant transformation method |
| JP3454818B1 (ja) | 2001-03-16 | 2003-10-06 | 直哉 小林 | 肝臓細胞の増殖方法、該方法により得られる肝臓細胞、およびその用途 |
| WO2002080851A2 (en) | 2001-04-05 | 2002-10-17 | The Johns Hopkins University | Chimeric vaccines |
| EP1412371B1 (en) | 2001-07-12 | 2016-02-24 | University of Massachusetts | IN VIVO PRODUCTION OF SMALL INTERFERING RNAs THAT MEDIATE GENE SILENCING |
| JP2005509409A (ja) | 2001-08-08 | 2005-04-14 | ジェンザイム・コーポレーション | 糖尿病および他の血糖疾患の治療方法 |
| WO2003016338A1 (en) | 2001-08-15 | 2003-02-27 | Parker Hughes Institute | Crystal structure of the btk kinase domain |
| WO2003045304A2 (en) | 2001-09-26 | 2003-06-05 | Mayo Foundation For Medical Education And Research | Mutable vaccines |
| US20090100536A1 (en) | 2001-12-04 | 2009-04-16 | Monsanto Company | Transgenic plants with enhanced agronomic traits |
| WO2003087993A2 (en) | 2002-04-09 | 2003-10-23 | Beattie Kenneth L | Oligonucleotide probes for genosensor chips |
| EP1532178A4 (en) | 2002-06-11 | 2006-10-25 | Scripps Research Inst | Artificial transcription factors |
| EP1546397A4 (en) | 2002-09-27 | 2007-10-31 | Cold Spring Harbor Lab | CELL BASED RNA INTERFERENCE AND ASSOCIATED METHODS AND COMPOSITIONS |
| AU2003290937A1 (en) | 2002-11-15 | 2004-06-15 | Trustees Of Boston University | Cis/trans riboregulators |
| US20060178297A1 (en) | 2003-01-28 | 2006-08-10 | Troy Carol M | Systems and methods for silencing expression of a gene in a cell and uses thereof |
| US7601492B2 (en) | 2003-07-03 | 2009-10-13 | The Regents Of The University Of California | Genome mapping of functional DNA elements and cellular proteins |
| US20070134796A1 (en) | 2005-07-26 | 2007-06-14 | Sangamo Biosciences, Inc. | Targeted integration and expression of exogenous nucleic acid sequences |
| AU2004263865B2 (en) * | 2003-08-08 | 2007-05-17 | Sangamo Therapeutics, Inc. | Methods and compositions for targeted cleavage and recombination |
| US20060171924A1 (en) * | 2003-10-03 | 2006-08-03 | Ke Luo | Bidirectional promoters for small RNA expression |
| FR2862659B1 (fr) | 2003-11-21 | 2006-02-10 | Pasteur Institut | Genome de legionella pneumophila souche paris- applications diagnostiques et epidemiologiques |
| US8053232B2 (en) | 2004-01-23 | 2011-11-08 | Virxsys Corporation | Correction of alpha-1-antitrypsin genetic defects using spliceosome mediated RNA trans splicing |
| US20070244031A1 (en) | 2004-01-27 | 2007-10-18 | Quan Lu | Methods and Compositions for Homozygous Gene Inactivation Using Collections of Pre-Defined Nucleotide Sequences Complementary Chromosomal Transcripts |
| US20050220796A1 (en) | 2004-03-31 | 2005-10-06 | Dynan William S | Compositions and methods for modulating DNA repair |
| FR2872170B1 (fr) | 2004-06-25 | 2006-11-10 | Centre Nat Rech Scient Cnrse | Lentivirus non interactif et non replicatif, preparation et utilisations |
| CN101277971A (zh) | 2004-07-16 | 2008-10-01 | 美国政府健康及人类服务部 | 含cmv/r-核酸构建体的抗aids疫苗 |
| AU2006239169A1 (en) | 2005-04-28 | 2006-11-02 | Benitec, Limited. | Multiple-RNAi expression cassettes for simultaneous delivery of RNAi agents related to heterozygotic expression patterns |
| US7892224B2 (en) | 2005-06-01 | 2011-02-22 | Brainlab Ag | Inverse catheter planning |
| EP3284833B1 (en) | 2005-08-26 | 2021-12-01 | DuPont Nutrition Biosciences ApS | Use of crispr associated genes (cas) |
| US8362229B2 (en) * | 2006-02-08 | 2013-01-29 | Quark Pharmaceuticals, Inc. | Tandem siRNAS |
| US9677123B2 (en) | 2006-03-15 | 2017-06-13 | Siemens Healthcare Diagnostics Inc. | Degenerate nucleobase analogs |
| WO2007134161A2 (en) | 2006-05-11 | 2007-11-22 | Alnylam Pharmaceuticals, Inc. | Compositions and methods for inhibiting expression of the pcsk9 gene |
| WO2008054544A2 (en) | 2006-05-22 | 2008-05-08 | Immune Disease Institute, Inc. | Method for delivery across the blood brain barrier |
| WO2008093152A1 (en) | 2007-02-01 | 2008-08-07 | Cellectis | Obligate heterodimer meganucleases and uses thereof |
| NZ579002A (en) | 2007-03-02 | 2012-03-30 | Danisco | Cultures with improved phage resistance |
| PE20090064A1 (es) | 2007-03-26 | 2009-03-02 | Novartis Ag | Acido ribonucleico de doble cadena para inhibir la expresion del gen e6ap humano y composicion farmaceutica que lo comprende |
| WO2009088786A1 (en) | 2007-12-31 | 2009-07-16 | Nanocor Therapeutics, Inc. | Rna interference for the treatment of heart failure |
| WO2009105690A2 (en) | 2008-02-21 | 2009-08-27 | Targeted Genetics Corporation | Devices and methods for delivering polynucleotides into retinal cells of the macula and fovea |
| US8546553B2 (en) | 2008-07-25 | 2013-10-01 | University Of Georgia Research Foundation, Inc. | Prokaryotic RNAi-like system and methods of use |
| US20100076057A1 (en) | 2008-09-23 | 2010-03-25 | Northwestern University | TARGET DNA INTERFERENCE WITH crRNA |
| US9404098B2 (en) | 2008-11-06 | 2016-08-02 | University Of Georgia Research Foundation, Inc. | Method for cleaving a target RNA using a Cas6 polypeptide |
| US8969353B2 (en) | 2008-11-07 | 2015-03-03 | Massachusetts Institute Of Technology | Aminoalcohol lipidoids and uses thereof |
| ES2627552T3 (es) | 2008-12-04 | 2017-07-28 | Sigma Aldrich Company | Edición de genoma en ratas usando nucleasas con dedos de cinc |
| US20110016540A1 (en) | 2008-12-04 | 2011-01-20 | Sigma-Aldrich Co. | Genome editing of genes associated with trinucleotide repeat expansion disorders in animals |
| NZ593618A (en) | 2008-12-10 | 2013-02-22 | Alnylam Pharmaceuticals Inc | Gnaq targeted dsrna compositions and methods for inhibiting expression |
| WO2010075424A2 (en) | 2008-12-22 | 2010-07-01 | The Regents Of University Of California | Compositions and methods for downregulating prokaryotic genes |
| EP2206723A1 (en) | 2009-01-12 | 2010-07-14 | Bonas, Ulla | Modular DNA-binding domains |
| US20110239315A1 (en) | 2009-01-12 | 2011-09-29 | Ulla Bonas | Modular dna-binding domains and methods of use |
| WO2011036510A1 (en) | 2009-09-24 | 2011-03-31 | Cellectis | Meganuclease variants cleaving the genome of the herpes simplex virus and uses thereof |
| 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 |
| AU2010275432A1 (en) | 2009-07-24 | 2012-02-02 | 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 |
| WO2011028929A2 (en) | 2009-09-03 | 2011-03-10 | The Regents Of The University Of California | Nitrate-responsive promoter |
| US8889394B2 (en) | 2009-09-07 | 2014-11-18 | Empire Technology Development Llc | Multiple domain proteins |
| EP2504439B1 (en) | 2009-11-27 | 2016-03-02 | BASF Plant Science Company GmbH | Optimized endonucleases and uses thereof |
| AU2010334799A1 (en) | 2009-12-23 | 2012-07-12 | Max-Planck-Gesellschaft Zur Forderung Der Wissenschaften E.V. | Influenza targets |
| EP2534163B1 (en) | 2010-02-09 | 2015-11-04 | 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 |
| US8927514B2 (en) | 2010-04-30 | 2015-01-06 | City Of Hope | Recombinant adeno-associated vectors for targeted treatment |
| EP2569425B1 (en) | 2010-05-10 | 2016-07-06 | The Regents of The University of 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 |
| WO2012012738A1 (en) * | 2010-07-23 | 2012-01-26 | Sigma-Aldrich Co., Llc | Genome editing using targeting endonucleases and single-stranded nucleic acids |
| US9081737B2 (en) | 2010-08-02 | 2015-07-14 | Integrated Dna Technologies, Inc. | Methods for predicting stability and melting temperatures of nucleic acid duplexes |
| US9549901B2 (en) | 2010-09-03 | 2017-01-24 | The Brigham And Women's Hospital, Inc. | Lipid-polymer hybrid particles |
| US9175280B2 (en) | 2010-10-12 | 2015-11-03 | Sangamo Biosciences, Inc. | Methods and compositions for treating hemophilia B |
| US9405700B2 (en) | 2010-11-04 | 2016-08-02 | Sonics, Inc. | Methods and apparatus for virtualization in an integrated circuit |
| SMT202400520T1 (it) | 2011-04-22 | 2025-01-14 | Univ California | Virioni di virus adeno-associato con capside variante e relativi metodi di utilizzo |
| PT2702160T (pt) | 2011-04-27 | 2020-07-30 | Amyris Inc | Métodos para modificação genómica |
| US20140113376A1 (en) | 2011-06-01 | 2014-04-24 | Rotem Sorek | Compositions and methods for downregulating prokaryotic genes |
| KR102061557B1 (ko) | 2011-09-21 | 2020-01-03 | 상가모 테라퓨틱스, 인코포레이티드 | 이식 유전자 발현의 조절을 위한 방법 및 조성물 |
| HK1200491A1 (en) | 2011-10-06 | 2015-08-07 | Sangamo Biosciences, Inc. | Methods and compositions for regulating hiv infection |
| EP2591770B1 (en) | 2011-11-14 | 2016-03-16 | Silenseed Ltd | Compositions for siRNA delivery and methods of manufacturing and using same |
| EP2780376B1 (en) | 2011-11-18 | 2017-03-08 | Université Laval | Methods and products for increasing frataxin levels and uses thereof |
| US10640785B2 (en) | 2011-11-22 | 2020-05-05 | The Children's Hospital Of Philadelphia | Virus vectors for highly efficient transgene delivery |
| US8450107B1 (en) | 2011-11-30 | 2013-05-28 | The Broad Institute Inc. | Nucleotide-specific recognition sequences for designer TAL effectors |
| GB201122458D0 (en) | 2011-12-30 | 2012-02-08 | Univ Wageningen | Modified cascade ribonucleoproteins and uses thereof |
| HK1203566A1 (zh) | 2012-02-29 | 2015-10-30 | 桑格摩生物科学股份有限公司 | 治療亨廷頓氏病的方法和組合物 |
| 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 |
| MY189533A (en) | 2012-05-25 | 2022-02-16 | Univ California | Methods and compositions for rna-directed target dna modification and for rna-directed modulation of transcription |
| AU2013267209B2 (en) | 2012-06-01 | 2017-02-02 | Baruch S. Blumberg Institute | Modulation of hepatitis B virus cccDNA transcription |
| ES2824024T3 (es) | 2012-10-10 | 2021-05-11 | Sangamo Therapeutics Inc | Compuestos modificadores de células T y usos de los mismos |
| WO2014065596A1 (en) | 2012-10-23 | 2014-05-01 | 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 |
| AU2013355214B2 (en) * | 2012-12-06 | 2017-06-15 | Sigma-Aldrich Co. Llc | Crispr-based genome modification and regulation |
| WO2014093479A1 (en) | 2012-12-11 | 2014-06-19 | Montana State University | Crispr (clustered regularly interspaced short palindromic repeats) rna-guided control of gene regulation |
| DK2921557T3 (en) | 2012-12-12 | 2016-11-07 | Broad Inst Inc | Design of systems, methods and optimized sequence manipulation guide compositions |
| CA2894668A1 (en) | 2012-12-12 | 2014-06-19 | The Broad Institute, Inc. | Crispr-cas systems and methods for altering expression of gene products in eukaryotic cells |
| WO2014093701A1 (en) | 2012-12-12 | 2014-06-19 | The Broad Institute, Inc. | Functional genomics using crispr-cas systems, compositions, methods, knock out libraries and applications thereof |
| WO2014093709A1 (en) | 2012-12-12 | 2014-06-19 | 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 |
| EP2931898B1 (en) | 2012-12-12 | 2016-03-09 | The Broad Institute, Inc. | Engineering and optimization of systems, methods and compositions for sequence manipulation with functional domains |
| CN105209621B (zh) | 2012-12-12 | 2021-05-25 | 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 |
| CN119752887A (zh) | 2012-12-12 | 2025-04-04 | 布罗德研究所有限公司 | 用于序列操纵的系统、方法和优化的指导组合物的工程化 |
| EP4299741A3 (en) | 2012-12-12 | 2024-02-28 | 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 |
| WO2014093694A1 (en) | 2012-12-12 | 2014-06-19 | The Broad Institute, Inc. | Crispr-cas nickase systems, methods and compositions for sequence manipulation in eukaryotes |
| EP4481048A3 (en) | 2012-12-17 | 2025-02-26 | President and Fellows of Harvard College | Rna-guided human genome engineering |
| CN104995302B (zh) | 2013-01-16 | 2021-08-31 | 爱默蕾大学 | Cas9-核酸复合物及其相关用途 |
| US10660943B2 (en) | 2013-02-07 | 2020-05-26 | The Rockefeller University | Sequence specific antimicrobials |
| US9163837B2 (en) | 2013-02-27 | 2015-10-20 | Siemens Aktiengesellschaft | Flow conditioner in a combustor of a gas turbine engine |
| WO2014150624A1 (en) | 2013-03-14 | 2014-09-25 | Caribou Biosciences, Inc. | Compositions and methods of nucleic acid-targeting nucleic acids |
| KR102210319B1 (ko) | 2013-03-15 | 2021-02-01 | 더 제너럴 하스피탈 코포레이션 | 특정 게놈 좌위에 대한 유전적 및 후성적 조절 단백질의 rna-안내 표적화 |
| KR102109069B1 (ko) | 2013-03-27 | 2020-05-12 | 윌코아게 | 디바이스들을 인라인 검사 및/또는 테스트하는 방법 및 그와 같은 방법을 수행하는 장치 |
| WO2014165349A1 (en) | 2013-04-04 | 2014-10-09 | Trustees Of Dartmouth College | Compositions and methods for in vivo excision of hiv-1 proviral dna |
| AU2014265331B2 (en) | 2013-05-15 | 2019-12-05 | Sangamo Therapeutics, Inc. | Methods and compositions for treatment of a genetic condition |
| US20160122774A1 (en) * | 2013-05-29 | 2016-05-05 | Cellectis | A method for producing precise dna cleavage using cas9 nickase activity |
| MY177814A (en) | 2013-06-04 | 2020-09-23 | Harvard College | Rna-guided transcriptional regulation |
| US9267135B2 (en) | 2013-06-04 | 2016-02-23 | President And Fellows Of Harvard College | RNA-guided transcriptional regulation |
| KR102733409B1 (ko) | 2013-06-05 | 2024-11-21 | 듀크 유니버시티 | Rna-가이드 유전자 편집 및 유전자 조절 |
| DK3011029T3 (da) | 2013-06-17 | 2020-03-16 | Broad Inst Inc | Administration, modificering og optimering af tandem-guidesystemer, fremgangsmåder og sammensætninger til sekvensmanipulering |
| 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 |
| WO2014204727A1 (en) | 2013-06-17 | 2014-12-24 | The Broad Institute Inc. | Functional genomics using crispr-cas systems, compositions methods, screens and applications thereof |
| EP3011031B1 (en) | 2013-06-17 | 2020-09-30 | The Broad Institute Inc. | Delivery and use of the crispr-cas systems, vectors and compositions for hepatic targeting and therapy |
| ES2767318T3 (es) | 2013-06-17 | 2020-06-17 | Broad Inst Inc | Suministro, modificación y optimización de sistemas, métodos y composiciones para generar modelos y actuar sobre enfermedades y trastornos de células posmitóticas |
| KR20160056869A (ko) | 2013-06-17 | 2016-05-20 | 더 브로드 인스티튜트, 인코퍼레이티드 | 바이러스 구성성분을 사용하여 장애 및 질환을 표적화하기 위한 crispr-cas 시스템 및 조성물의 전달, 용도 및 치료 적용 |
| DK3019619T3 (da) | 2013-07-11 | 2021-10-11 | Modernatx Inc | Sammensætninger, der omfatter syntetiske polynukleotider, som koder for crispr-beslægtede proteiner, og syntetiske sgrna'er, og anvendelsesfremgangsmåder |
| 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 |
| CN106102781A (zh) | 2013-08-29 | 2016-11-09 | 英联邦高等教育系统天普大学 | 用于hiv感染的rna指导的治疗的方法和组合物 |
| US9737604B2 (en) | 2013-09-06 | 2017-08-22 | President And Fellows Of Harvard College | Use of cationic lipids to deliver CAS9 |
| US9322037B2 (en) | 2013-09-06 | 2016-04-26 | President And Fellows Of Harvard College | Cas9-FokI fusion proteins and uses thereof |
| WO2015048577A2 (en) | 2013-09-27 | 2015-04-02 | Editas Medicine, Inc. | Crispr-related methods and compositions |
| WO2015065964A1 (en) | 2013-10-28 | 2015-05-07 | The Broad Institute Inc. | Functional genomics using crispr-cas systems, compositions, methods, screens and applications thereof |
| PT3066201T (pt) | 2013-11-07 | 2018-06-04 | Massachusetts Inst Technology | Métodos e composições relacionadas com crispr com arng reguladores |
| EP3760719A1 (en) | 2013-11-18 | 2021-01-06 | CRISPR Therapeutics AG | Crispr-cas system materials and methods |
| WO2015089419A2 (en) | 2013-12-12 | 2015-06-18 | 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 |
| 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 |
| CN106103705A (zh) | 2013-12-12 | 2016-11-09 | 布罗德研究所有限公司 | 核苷酸重复障碍中crispr‑cas系统的组合物和使用方法 |
| WO2015089364A1 (en) | 2013-12-12 | 2015-06-18 | The Broad Institute Inc. | Crystal structure of a crispr-cas system, and uses thereof |
| CN103668472B (zh) | 2013-12-31 | 2014-12-24 | 北京大学 | 利用CRISPR/Cas9系统构建真核基因敲除文库的方法 |
| WO2015113063A1 (en) | 2014-01-27 | 2015-07-30 | Georgia Tech Research Corporation | Methods and systems for identifying crispr/cas off-target sites |
| JP6323228B2 (ja) | 2014-07-18 | 2018-05-16 | 富士電機株式会社 | 電力変換装置 |
| WO2016022866A1 (en) | 2014-08-07 | 2016-02-11 | Agilent Technologies, Inc. | Cis-blocked guide rna |
| WO2016028682A1 (en) | 2014-08-17 | 2016-02-25 | The Broad Institute Inc. | Genome editing using cas9 nickases |
| US9944912B2 (en) | 2015-03-03 | 2018-04-17 | The General Hospital Corporation | Engineered CRISPR-Cas9 nucleases with altered PAM specificity |
| KR102840885B1 (ko) | 2015-06-18 | 2025-07-30 | 더 브로드 인스티튜트, 인코퍼레이티드 | 표적외 효과를 감소시키는 crispr 효소 돌연변이 |
| US9512446B1 (en) | 2015-08-28 | 2016-12-06 | The General Hospital Corporation | Engineered CRISPR-Cas9 nucleases |
| JP6186470B2 (ja) | 2016-04-20 | 2017-08-23 | パイオニア株式会社 | 音響装置、音量制御方法、音量制御プログラム及び記録媒体 |
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2014
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- 2014-06-10 JP JP2016521449A patent/JP6625971B2/ja active Active
- 2014-06-10 AU AU2014281026A patent/AU2014281026B2/en active Active
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| US20160186213A1 (en) | 2016-06-30 |
| EP3674411A1 (en) | 2020-07-01 |
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| WO2014204724A9 (en) | 2016-03-24 |
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| JP2020054354A (ja) | 2020-04-09 |
| CA2915834A1 (en) | 2014-12-24 |
| CN106062197A (zh) | 2016-10-26 |
| AU2014281026A9 (en) | 2016-06-16 |
| KR20160044457A (ko) | 2016-04-25 |
| EP3011029A1 (en) | 2016-04-27 |
| EP3011029B1 (en) | 2019-12-11 |
| AU2014281026B2 (en) | 2020-05-28 |
| HK1223646A1 (en) | 2017-08-04 |
| WO2014204724A8 (en) | 2015-12-23 |
| JP2016521993A (ja) | 2016-07-28 |
| JP6625971B2 (ja) | 2019-12-25 |
| DK3011029T3 (da) | 2020-03-16 |
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