TW201839136A - 治療血色素異常症之組合物及方法 - Google Patents
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| US12043852B2 (en) | 2015-10-23 | 2024-07-23 | President And Fellows Of Harvard College | Evolved Cas9 proteins for gene editing |
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| CA3057192A1 (en) | 2017-03-23 | 2018-09-27 | President And Fellows Of Harvard College | Nucleobase editors comprising nucleic acid programmable dna binding proteins |
| WO2018209158A2 (en) | 2017-05-10 | 2018-11-15 | Editas Medicine, Inc. | Crispr/rna-guided nuclease systems and methods |
| WO2018209320A1 (en) | 2017-05-12 | 2018-11-15 | President And Fellows Of Harvard College | Aptazyme-embedded guide rnas for use with crispr-cas9 in genome editing and transcriptional activation |
| US20200140896A1 (en) * | 2017-06-30 | 2020-05-07 | Novartis Ag | Methods for the treatment of disease with gene editing systems |
| EP3652312A1 (en) | 2017-07-14 | 2020-05-20 | Editas Medicine, Inc. | Systems and methods for targeted integration and genome editing and detection thereof using integrated priming sites |
| 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 |
| WO2019139645A2 (en) | 2017-08-30 | 2019-07-18 | President And Fellows Of Harvard College | High efficiency base editors comprising gam |
| CA3082251A1 (en) | 2017-10-16 | 2019-04-25 | The Broad Institute, Inc. | Uses of adenosine base editors |
| US20210180053A1 (en) | 2017-11-01 | 2021-06-17 | Novartis Ag | Synthetic rnas and methods of use |
| KR20220066413A (ko) | 2017-12-14 | 2022-05-24 | 프로디자인 소닉스, 인크. | 음향 트랜스듀서 구동기 및 제어기 |
| EP3724214A4 (en) | 2017-12-15 | 2021-09-01 | The Broad Institute Inc. | SYSTEMS AND METHODS FOR PREDICTING REPAIR RESULTS IN GENETIC ENGINEERING |
| SG11202008956XA (en) | 2018-03-14 | 2020-10-29 | Editas Medicine Inc | Systems and methods for the treatment of hemoglobinopathies |
| US12133884B2 (en) | 2018-05-11 | 2024-11-05 | Beam Therapeutics Inc. | Methods of substituting pathogenic amino acids using programmable base editor systems |
| WO2019226953A1 (en) | 2018-05-23 | 2019-11-28 | The Broad Institute, Inc. | Base editors and uses thereof |
| US12281338B2 (en) | 2018-10-29 | 2025-04-22 | The Broad Institute, Inc. | Nucleobase editors comprising GeoCas9 and uses thereof |
| EP3887521A1 (en) * | 2018-11-29 | 2021-10-06 | Editas Medicine, Inc. | Systems and methods for the treatment of hemoglobinopathies |
| WO2020112195A1 (en) * | 2018-11-30 | 2020-06-04 | Yale University | Compositions, technologies and methods of using plerixafor to enhance gene editing |
| KR20210102309A (ko) * | 2018-12-05 | 2021-08-19 | 프레드 헛친슨 켄서 리서치 센터 | 유전적으로-변형된 세포를 제작하는 줄어든, 그리고 최소한의 조작 |
| US12351837B2 (en) | 2019-01-23 | 2025-07-08 | The Broad Institute, Inc. | Supernegatively charged proteins and uses thereof |
| AU2020223060B2 (en) | 2019-02-13 | 2023-04-13 | Beam Therapeutics Inc. | Compositions and methods for treating hemoglobinopathies |
| DE112020001306T5 (de) | 2019-03-19 | 2022-01-27 | Massachusetts Institute Of Technology | Verfahren und zusammensetzungen zur editierung von nukleotidsequenzen |
| US12473543B2 (en) | 2019-04-17 | 2025-11-18 | The Broad Institute, Inc. | Adenine base editors with reduced off-target effects |
| CN111939271A (zh) * | 2019-04-30 | 2020-11-17 | 博雅辑因（北京）生物科技有限公司 | 一种血红蛋白病治疗有效性预测方法 |
| PE20220003A1 (es) * | 2019-04-30 | 2022-01-05 | Edigene Inc | Metodo para la prediccion de eficacia del tratamiento de hemoglobinopatia |
| CN110106203B (zh) * | 2019-05-24 | 2023-08-11 | 中国医学科学院血液病医院（血液学研究所） | 一种新型hbb过表达载体及其设计方法和应用 |
| US12435330B2 (en) | 2019-10-10 | 2025-10-07 | The Broad Institute, Inc. | Methods and compositions for prime editing RNA |
| EP4054710A4 (en) * | 2019-11-06 | 2023-12-06 | Syros Pharmaceuticals, Inc. | Compositions and methods for treating sickle cell disease |
| BR112022020407A2 (pt) * | 2020-04-09 | 2023-05-02 | Verve Therapeutics Inc | Edição base do pcsk9 e métodos de uso do mesmo para tratamento de doenças |
| JP2023525304A (ja) | 2020-05-08 | 2023-06-15 | ザ ブロード インスティテュート，インコーポレーテッド | 標的二本鎖ヌクレオチド配列の両鎖同時編集のための方法および組成物 |
| CN111575306B (zh) * | 2020-06-11 | 2022-08-05 | 南方医科大学 | 一种激活红细胞中γ珠蛋白基因表达的方法 |
| EP4196260A4 (en) * | 2020-08-14 | 2025-04-30 | Navan Technologies, Inc. | METHODS AND APPARATUS FOR DELIVERING BIOMOLECULES TO PRIMARY HUMAN HEMATOPOIETIC STEM CELLS USING NANOSTRAWS |
| WO2022170059A1 (en) | 2021-02-05 | 2022-08-11 | Christiana Care Health Services, Inc. | Methods of and compositions for reducing gene expression and/or activity |
| US20250179531A1 (en) * | 2022-02-25 | 2025-06-05 | Vor Biopharma Inc. | Compositions and methods for homology-directed repair gene modification |
| WO2024163679A1 (en) * | 2023-02-01 | 2024-08-08 | Prime Medicine, Inc. | Genome editing compositions and methods for treatment of cystic fibrosis |
| CN116445402B (zh) * | 2023-05-09 | 2025-04-25 | 中国科学院生态环境研究中心 | 红系祖细胞的扩增培养基、扩增培养方法及应用 |
| WO2024254566A2 (en) * | 2023-06-08 | 2024-12-12 | Editas Medicine, Inc. | Systems and methods for the treatment of hemoglobinopathies |
| WO2025128871A2 (en) | 2023-12-13 | 2025-06-19 | Renagade Therapeutics Management Inc. | Lipid nanoparticles comprising coding rna molecules for use in gene editing and as vaccines and therapeutic agents |
| WO2025174765A1 (en) | 2024-02-12 | 2025-08-21 | Renagade Therapeutics Management Inc. | Lipid nanoparticles comprising coding rna molecules for use in gene editing and as vaccines and therapeutic agents |
Family Cites Families (237)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5800815A (en) | 1903-05-05 | 1998-09-01 | Cytel Corporation | Antibodies to P-selectin and their uses |
| US6309639B1 (en) | 1991-02-05 | 2001-10-30 | The Board Of Regents Of The University Of Oklahoma | Method for inhibiting an inflammatory response using antibodies to P-selectin glycoprotein ligand |
| US5213796A (en) | 1991-05-06 | 1993-05-25 | Dana Farber Cancer Institute | Assay for polyomavirus in humans and uses thereof |
| US5726014A (en) | 1991-06-27 | 1998-03-10 | Genelabs Technologies, Inc. | Screening assay for the detection of DNA-binding molecules |
| US5578444A (en) | 1991-06-27 | 1996-11-26 | Genelabs Technologies, Inc. | Sequence-directed DNA-binding molecules compositions and methods |
| DE69332881T2 (de) | 1992-05-05 | 2004-01-29 | Aeres Biomedical Ltd | Antikörper gegen p-selectin und ihre verwendung |
| US7910624B1 (en) | 1995-03-03 | 2011-03-22 | The Trustees Of Boston University | Compositions for the treatment of blood disorders |
| AU696167B2 (en) | 1993-10-29 | 1998-09-03 | Trustees Of Boston University | Physiologically stable compositions of butyric acid, and butyric acid salts and derivatives as anti-neoplastic agents |
| US5622701A (en) | 1994-06-14 | 1997-04-22 | Protein Design Labs, Inc. | Cross-reacting monoclonal antibodies specific for E- and P-selectin |
| US6453242B1 (en) | 1999-01-12 | 2002-09-17 | Sangamo Biosciences, Inc. | Selection of sites for targeting by zinc finger proteins and methods of designing zinc finger proteins to bind to preselected sites |
| US6534261B1 (en) | 1999-01-12 | 2003-03-18 | Sangamo Biosciences, Inc. | Regulation of endogenous gene expression in cells using zinc finger proteins |
| US6599692B1 (en) | 1999-09-14 | 2003-07-29 | Sangamo Bioscience, Inc. | Functional genomics using zinc finger proteins |
| US7013219B2 (en) | 1999-01-12 | 2006-03-14 | Sangamo Biosciences, Inc. | Regulation of endogenous gene expression in cells using zinc finger proteins |
| US7070934B2 (en) | 1999-01-12 | 2006-07-04 | Sangamo Biosciences, Inc. | Ligand-controlled regulation of endogenous gene expression |
| US6780590B2 (en) | 1999-09-14 | 2004-08-24 | Sangamo Biosciences, Inc. | Gene identification |
| US20020164575A1 (en) | 1999-09-14 | 2002-11-07 | Sangamo Biosciences, Inc., A Delaware Corporation | Gene identification |
| 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 |
| IT1320168B1 (it) | 2000-03-13 | 2003-11-18 | Univ Ferrara | Oligonucleotidi sintetici in grado di indurre il differenziamentoeritroide. |
| WO2001085765A2 (en) | 2000-05-12 | 2001-11-15 | Merck Patent Gmbh | Identification of mfq-110, a human c2h2-type zinc finger protein |
| US20050054836A1 (en) | 2000-11-09 | 2005-03-10 | Cold Spring Harbor Laboratory | Chimeric molecules to modulate gene expression |
| WO2002044386A2 (en) | 2000-12-01 | 2002-06-06 | Sangamo Biosciences, Inc. | Targeted regulation of gene expression |
| AU2002309583A1 (en) | 2001-04-18 | 2002-11-05 | Protein Desing Labs, Inc. | Methods of diagnosis of lung cancer, compositions and methods of screening for modulators of lung cancer |
| US8735153B2 (en) | 2001-09-24 | 2014-05-27 | Sangamo Biosciences, Inc. | Modulation of stem cells using zinc finger proteins |
| JP2006502748A (ja) | 2002-09-05 | 2006-01-26 | カリフォルニア インスティテュート オブ テクノロジー | 遺伝子ターゲッティングを誘発するキメラヌクレアーゼの使用方法 |
| EP1581056B1 (en) | 2002-12-13 | 2010-07-21 | Genetix Pharmaceuticals Inc. | Therapeutic retroviral vectors for gene therapy |
| WO2004098508A2 (en) | 2003-04-30 | 2004-11-18 | Napro Biotherapeutics, Inc. | Methods for production of non-disease causing hemoglobin by ex vivo oligonucleotide gene editing of human stem/progenitor cells |
| US7888121B2 (en) | 2003-08-08 | 2011-02-15 | Sangamo Biosciences, Inc. | Methods and compositions for targeted cleavage and recombination |
| US8409861B2 (en) | 2003-08-08 | 2013-04-02 | Sangamo Biosciences, Inc. | Targeted deletion of cellular DNA sequences |
| EP3222715A1 (en) | 2003-08-08 | 2017-09-27 | Sangamo BioSciences, Inc. | Methods and compositions for targeted cleavage and recombination |
| WO2005060697A2 (en) | 2003-12-19 | 2005-07-07 | Chiron Corporation | Cell transfecting formulations of small interfering rna, related compositions and methods of making and use |
| US20050244851A1 (en) | 2004-01-13 | 2005-11-03 | Affymetrix, Inc. | Methods of analysis of alternative splicing in human |
| US7972854B2 (en) | 2004-02-05 | 2011-07-05 | Sangamo Biosciences, Inc. | Methods and compositions for targeted cleavage and recombination |
| BR122019012028B1 (pt) | 2004-04-13 | 2023-09-26 | F. Hoffmann-La Roche Ag | Anticorpos anti-p-selectina, molécula de ácido nucléico, vetor, e composição |
| US20100055793A1 (en) | 2005-07-25 | 2010-03-04 | Johns Hopkins University | Site-specific modification of the human genome using custom-designed zinc finger nucleases |
| US8377440B2 (en) | 2006-12-01 | 2013-02-19 | Selexys Pharmaceuticals Corporation | Anti-P-selectin antibodies and methods of using the same to treat inflammatory diseases |
| US20110212096A1 (en) | 2006-12-01 | 2011-09-01 | Scott Rollins | Anti-p-selectin antibodies and methods of their use and identification |
| US8945565B2 (en) | 2006-12-01 | 2015-02-03 | Selexys Pharmaceuticals Corporation | Methods of treating inflammatory or thrombotic conditions with anti-P-selectin antibodies |
| GB0713183D0 (en) | 2007-07-06 | 2007-08-15 | King S College London | Method |
| WO2010030963A2 (en) | 2008-09-15 | 2010-03-18 | Children's Medical Center Corporation | Modulation of bcl11a for treatment of hemoglobinopathies |
| PE20100362A1 (es) | 2008-10-30 | 2010-05-27 | Irm Llc | Derivados de purina que expanden las celulas madre hematopoyeticas |
| EP3721943A1 (en) | 2009-12-23 | 2020-10-14 | Novartis AG | Lipids, lipid compositions and methods of using them |
| WO2011103215A1 (en) | 2010-02-16 | 2011-08-25 | Mount Sinai School Of Medicine | Embedded chimeric peptide nucleic acids and use thereof |
| WO2012075027A1 (en) | 2010-11-29 | 2012-06-07 | Mount Sinai School Of Medicine | Embedded chimeric peptide nucleic acids for generation of induced pluripotent stem cells |
| BR112013000244A2 (pt) | 2010-07-06 | 2016-05-17 | Novartis Ag | lipossomas com lipídeos apresentando pka vantajoso para administração de rna |
| US20140127814A1 (en) | 2010-08-10 | 2014-05-08 | Srinivasan Chandrasegaran | Generation and use of pluripotent stem cells |
| JP5908477B2 (ja) | 2010-08-31 | 2016-04-26 | ノバルティス アーゲー | タンパク質をコードするｒｎａのリポソームによる送達に適した脂質 |
| US9127275B2 (en) | 2010-12-10 | 2015-09-08 | Alnylam Pharmaceuticals, Inc. | Compositions and methods for inhibiting expression of klf-1 and bcl11a genes |
| WO2012112232A1 (en) | 2011-02-18 | 2012-08-23 | Academia Sinica | METHODS AND COMPOSITIONS FOR TREATING β-THALASSEMIA AND SICKLE CELL DISEASE |
| DE202011050611U1 (de) | 2011-07-01 | 2012-10-09 | Makita Corporation | Anordnung zum Bereitstellen eines Kraftstoff-Luftgemischs für eine Brennkraftmaschine |
| EP4115875A1 (en) | 2011-07-06 | 2023-01-11 | GlaxoSmithKline Biologicals S.A. | Liposomes having useful n:p ratio for delivery of rna molecules |
| WO2013019745A1 (en) | 2011-07-29 | 2013-02-07 | Georgia Health Sciences University | Methods and compositions for genetically modifiying cells |
| WO2013055985A1 (en) | 2011-10-12 | 2013-04-18 | Children's Medical Center Corporation | Combinatorial compositions and methods of treating hemoglobinopathies |
| JP6219832B2 (ja) | 2011-10-17 | 2017-10-25 | マサチューセッツ インスティテュート オブ テクノロジー | 細胞内送達 |
| US9394547B2 (en) | 2012-01-03 | 2016-07-19 | City University Of Hong Kong | Method and apparatus for delivery of molecules to cells |
| WO2013103467A1 (en) | 2012-01-06 | 2013-07-11 | Alcon Research, Ltd. | Interfering rna delivery system and uses thereof |
| SI2807165T1 (sl) | 2012-01-27 | 2019-08-30 | Universite De Montreal | Pirimido(4,5-B)indol derivati in njihova uporaba pri ekspanziji hematopoetskih matičnih celic |
| CN104284669A (zh) | 2012-02-24 | 2015-01-14 | 弗雷德哈钦森癌症研究中心 | 治疗血红蛋白病的组合物和方法 |
| ES2828663T3 (es) | 2012-04-18 | 2021-05-27 | Univ Leland Stanford Junior | Dirección genética no disruptiva |
| US20150017136A1 (en) | 2013-07-15 | 2015-01-15 | Cellectis | Methods for engineering allogeneic and highly active t cell for immunotherapy |
| CA3133545C (en) | 2012-05-25 | 2023-08-08 | Cellectis | Use of pre t alpha or functional variant thereof for expanding tcr alpha deficient t cells |
| FI3597749T3 (fi) | 2012-05-25 | 2023-10-09 | Univ California | Menetelmiä ja koostumuksia rna-ohjattua kohde-dna-modifikaatiota varten ja rna-ohjattua transkription modulaatiota varten |
| 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 |
| WO2014011901A2 (en) | 2012-07-11 | 2014-01-16 | Sangamo Biosciences, Inc. | Methods and compositions for delivery of biologics |
| EP2877213B1 (en) | 2012-07-25 | 2020-12-02 | The Broad Institute, Inc. | Inducible dna binding proteins and genome perturbation tools and applications thereof |
| AU2013308770B2 (en) | 2012-08-29 | 2019-01-17 | Sangamo Therapeutics, Inc. | Methods and compositions for treatment of a genetic condition |
| AU2013312838B2 (en) | 2012-09-04 | 2018-11-29 | Cellectis | Multi-chain chimeric antigen receptor and uses thereof |
| KR101656236B1 (ko) | 2012-10-23 | 2016-09-12 | 주식회사 툴젠 | 표적 DNA에 특이적인 가이드 RNA 및 Cas 단백질을 암호화하는 핵산 또는 Cas 단백질을 포함하는, 표적 DNA를 절단하기 위한 조성물 및 이의 용도 |
| AU2013352156B2 (en) | 2012-11-27 | 2018-12-06 | Children's Medical Center Corporation | Targeting BCL11A distal regulatory elements for fetal hemoglobin reinduction |
| PT3363902T (pt) | 2012-12-06 | 2019-12-19 | Sigma Aldrich Co Llc | Modificação e regulação de genoma baseadas em crispr |
| US8697359B1 (en) | 2012-12-12 | 2014-04-15 | The Broad Institute, Inc. | CRISPR-Cas systems and methods for altering expression of gene products |
| EP3434776A1 (en) | 2012-12-12 | 2019-01-30 | The Broad Institute, Inc. | Methods, models, systems, and apparatus for identifying target sequences for cas enzymes or crispr-cas systems for target sequences and conveying results thereof |
| PT2784162E (pt) | 2012-12-12 | 2015-08-27 | Broad Inst Inc | Engenharia de sistemas, métodos e composições guia otimizadas para a manipulação de sequências |
| EP4234696A3 (en) | 2012-12-12 | 2023-09-06 | The Broad Institute Inc. | Crispr-cas component systems, methods and compositions for sequence manipulation |
| US20140310830A1 (en) | 2012-12-12 | 2014-10-16 | Feng Zhang | CRISPR-Cas Nickase Systems, Methods And Compositions For Sequence Manipulation in Eukaryotes |
| ES2576126T3 (es) | 2012-12-12 | 2016-07-05 | The Broad Institute, Inc. | Modificación por tecnología genética y optimización de sistemas, métodos y composiciones enzimáticas mejorados para la manipulación de secuencias |
| KR20150105956A (ko) | 2012-12-12 | 2015-09-18 | 더 브로드 인스티튜트, 인코퍼레이티드 | 서열 조작 및 치료적 적용을 위한 시스템, 방법 및 조성물의 전달, 유전자 조작 및 최적화 |
| EP2931899A1 (en) | 2012-12-12 | 2015-10-21 | The Broad Institute, Inc. | Functional genomics using crispr-cas systems, compositions, methods, knock out libraries and applications thereof |
| EP2932421A1 (en) | 2012-12-12 | 2015-10-21 | The Broad Institute, Inc. | Methods, 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 |
| EP4282970A3 (en) | 2012-12-17 | 2024-01-17 | President and Fellows of Harvard College | Rna-guided human genome engineering |
| CA2901676C (en) | 2013-02-25 | 2023-08-22 | Sangamo Biosciences, Inc. | Methods and compositions for enhancing nuclease-mediated gene disruption |
| ES2750550T3 (es) | 2013-03-01 | 2020-03-26 | Univ Minnesota | Corrección de gen a base de TALEN |
| CN107879960B (zh) | 2013-03-08 | 2021-06-22 | 诺华股份有限公司 | 用于传递活性成分的脂质和脂质组合物 |
| US10612043B2 (en) | 2013-03-09 | 2020-04-07 | Agilent Technologies, Inc. | Methods of in vivo engineering of large sequences using multiple CRISPR/cas selections of recombineering events |
| AU2014235794A1 (en) | 2013-03-14 | 2015-10-22 | Caribou Biosciences, Inc. | Compositions and methods of nucleic acid-targeting nucleic acids |
| US11332719B2 (en) | 2013-03-15 | 2022-05-17 | The Broad Institute, Inc. | Recombinant virus and preparations thereof |
| 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 |
| US9234213B2 (en) | 2013-03-15 | 2016-01-12 | System Biosciences, Llc | Compositions and methods directed to CRISPR/Cas genomic engineering systems |
| HUE042072T2 (hu) | 2013-03-15 | 2019-06-28 | Glaxosmithkline Biologicals Sa | Eljárások RNS tisztítására |
| US20140273230A1 (en) | 2013-03-15 | 2014-09-18 | Sigma-Aldrich Co., Llc | Crispr-based genome modification and regulation |
| KR102874079B1 (ko) | 2013-03-15 | 2025-10-22 | 더 제너럴 하스피탈 코포레이션 | Rna-안내 게놈 편집을 위해 특이성을 증가시키기 위한 절단된 안내 rna(tru-grnas)의 이용 |
| EP2968295A1 (en) | 2013-03-15 | 2016-01-20 | Global Blood Therapeutics, Inc. | Compositions and methods for the modulation of hemoglobin (s) |
| US11274305B2 (en) | 2013-04-04 | 2022-03-15 | Trustees Of Dartmouth College | Compositions and methods for in vivo excision of HIV-1 proviral DNA |
| US20150056629A1 (en) | 2013-04-14 | 2015-02-26 | Katriona Guthrie-Honea | Compositions, systems, and methods for detecting a DNA sequence |
| WO2014172470A2 (en) | 2013-04-16 | 2014-10-23 | Whitehead Institute For Biomedical Research | Methods of mutating, modifying or modulating nucleic acid in a cell or nonhuman mammal |
| AU2014266833B2 (en) | 2013-05-13 | 2020-07-02 | Cellectis | Methods for engineering highly active T cell for immunotherapy |
| RS65484B1 (sr) | 2013-05-13 | 2024-05-31 | Cellectis | Cd19 specifični himerni antigenski receptor i njegove primene |
| AU2014265331B2 (en) | 2013-05-15 | 2019-12-05 | Sangamo Therapeutics, Inc. | Methods and compositions for treatment of a genetic condition |
| BR112015029327A2 (pt) | 2013-05-24 | 2017-09-19 | Roche Innovation Ct Copenhagen As | Moduladores de oligonucleotídeo de linfoma 11a/cll de célula b (bcl11a) e usos dos mesmos |
| DK3004337T3 (da) | 2013-05-29 | 2017-11-13 | Cellectis | Fremgangsmåde til konstruktion af T-celler til immunoterapi ved brug af RNA-guidet Cas nuklease-system |
| US11685935B2 (en) | 2013-05-29 | 2023-06-27 | Cellectis | Compact scaffold of Cas9 in the type II CRISPR system |
| RU2690935C2 (ru) | 2013-06-04 | 2019-06-06 | Президент Энд Фэллоуз Оф Харвард Коллидж | Направляемая рнк регуляция транскрипции |
| US20140356956A1 (en) | 2013-06-04 | 2014-12-04 | President And Fellows Of Harvard College | RNA-Guided Transcriptional Regulation |
| JP7085716B2 (ja) * | 2013-06-05 | 2022-06-17 | デューク ユニバーシティ | Ｒｎａガイド遺伝子編集及び遺伝子調節 |
| EP4491726A3 (en) | 2013-06-11 | 2025-03-05 | Takara Bio USA, Inc. | Protein enriched microvesicles and methods of making and using the same |
| US20150315252A1 (en) | 2013-06-11 | 2015-11-05 | Clontech Laboratories, Inc. | Protein enriched microvesicles and methods of making and using the same |
| CN107995927B (zh) | 2013-06-17 | 2021-07-30 | 布罗德研究所有限公司 | 用于肝靶向和治疗的crispr-cas系统、载体和组合物的递送与用途 |
| EP3011035B1 (en) | 2013-06-17 | 2020-05-13 | The Broad Institute, Inc. | Assay for quantitative evaluation of target site cleavage by one or more crispr-cas guide sequences |
| JP6738729B2 (ja) | 2013-06-17 | 2020-08-12 | ザ・ブロード・インスティテュート・インコーポレイテッド | 分裂終了細胞の疾患および障害をターゲティングおよびモデリングするための系、方法および組成物の送達、エンジニアリングおよび最適化 |
| CA2915795C (en) | 2013-06-17 | 2021-07-13 | The Broad Institute, Inc. | Delivery, use and therapeutic applications of the crispr-cas systems and compositions for targeting disorders and diseases using viral components |
| EP3725885A1 (en) | 2013-06-17 | 2020-10-21 | The Broad Institute, Inc. | Functional genomics using crispr-cas systems, compositions methods, screens and applications thereof |
| EP3674411A1 (en) | 2013-06-17 | 2020-07-01 | The Broad Institute, Inc. | Delivery, engineering and optimization of tandem guide systems, methods and compositions for sequence manipulation |
| 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 |
| CN104239331B (zh) | 2013-06-19 | 2018-10-09 | 阿里巴巴集团控股有限公司 | 一种用于实现评论搜索引擎排序的方法和装置 |
| US10011850B2 (en) | 2013-06-21 | 2018-07-03 | The General Hospital Corporation | Using RNA-guided FokI Nucleases (RFNs) to increase specificity for RNA-Guided Genome Editing |
| EP3019595A4 (en) | 2013-07-09 | 2016-11-30 | THERAPEUTIC USES OF A GENERIC CHANGE WITH CRISPR / CAS SYSTEMS | |
| SG10201800213VA (en) | 2013-07-10 | 2018-02-27 | Harvard College | Orthogonal cas9 proteins for rna-guided gene regulation and editing |
| 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 |
| WO2015021426A1 (en) | 2013-08-09 | 2015-02-12 | Sage Labs, Inc. | A crispr/cas system-based novel fusion protein and its application in genome editing |
| PL3033184T3 (pl) | 2013-08-16 | 2021-09-20 | Massachusetts Institute Of Technology | Selektywne dostarczanie materiału do komórek |
| EP3611268A1 (en) | 2013-08-22 | 2020-02-19 | E. I. du Pont de Nemours and Company | Plant genome modification using guide rna/cas endonuclease systems and methods of use |
| GB201315321D0 (en) | 2013-08-28 | 2013-10-09 | Koninklijke Nederlandse Akademie Van Wetenschappen | Transduction Buffer |
| WO2015034872A2 (en) | 2013-09-05 | 2015-03-12 | Massachusetts Institute Of Technology | Tuning microbial populations with programmable nucleases |
| US9388430B2 (en) | 2013-09-06 | 2016-07-12 | President And Fellows Of Harvard College | Cas9-recombinase 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 |
| EP3988649B1 (en) | 2013-09-18 | 2024-11-27 | Kymab Limited | Methods, cells and organisms |
| US20160237455A1 (en) | 2013-09-27 | 2016-08-18 | Editas Medicine, Inc. | Crispr-related methods and compositions |
| US10822606B2 (en) | 2013-09-27 | 2020-11-03 | The Regents Of The University Of California | Optimized small guide RNAs and methods of use |
| JP5774657B2 (ja) | 2013-10-04 | 2015-09-09 | 国立大学法人京都大学 | エレクトロポレーションを利用した哺乳類の遺伝子改変方法 |
| WO2015052231A2 (en) | 2013-10-08 | 2015-04-16 | Technical University Of Denmark | Multiplex editing system |
| WO2015054507A1 (en) | 2013-10-10 | 2015-04-16 | Pronutria, Inc. | Nutritive polypeptide production systems, and methods of manufacture and use thereof |
| WO2015065964A1 (en) | 2013-10-28 | 2015-05-07 | The Broad Institute Inc. | Functional genomics using crispr-cas systems, compositions, methods, screens and applications thereof |
| US9850497B2 (en) | 2013-11-04 | 2017-12-26 | Regents Of The University Of Minnesota | Gene targeting methods and tools |
| KR20230054509A (ko) | 2013-11-07 | 2023-04-24 | 에디타스 메디신, 인코포레이티드 | 지배적인 gRNA를 이용하는 CRISPR-관련 방법 및 조성물 |
| DK3492593T3 (da) | 2013-11-13 | 2021-11-08 | Childrens Medical Center | Nukleasemedieret regulering af genekspression |
| US20160298096A1 (en) | 2013-11-18 | 2016-10-13 | Crispr Therapeutics Ag | Crispr-cas system materials and methods |
| WO2015075195A1 (en) | 2013-11-22 | 2015-05-28 | Cellectis | Method of engineering chemotherapy drug resistant t-cells for immunotherapy |
| CA2928635C (en) | 2013-11-28 | 2022-06-21 | Horizon Genomics Gmbh | Somatic haploid human cell line |
| BR112016013201B1 (pt) | 2013-12-12 | 2023-01-31 | The Broad Institute, Inc. | Uso de uma composição compreendendo um sistema crispr-cas no tratamento de uma doença genética ocular |
| EP3080271B1 (en) | 2013-12-12 | 2020-02-12 | The Broad Institute, Inc. | Systems, methods and compositions for sequence manipulation with optimized functional crispr-cas systems |
| EP3080266B1 (en) | 2013-12-12 | 2021-02-03 | The Regents of The University of California | Methods and compositions for modifying a single stranded target nucleic acid |
| JP2017503485A (ja) | 2013-12-12 | 2017-02-02 | ザ・ブロード・インスティテュート・インコーポレイテッド | 遺伝子産物の発現、構造情報、及び誘導性モジュラーｃａｓ酵素を変更するためのｃｒｉｓｐｒ−ｃａｓ系並びに方法 |
| SG10201804973TA (en) | 2013-12-12 | 2018-07-30 | Broad Inst Inc | Compositions and Methods of Use of Crispr-Cas Systems in Nucleotide Repeat Disorders |
| 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 |
| WO2015089364A1 (en) | 2013-12-12 | 2015-06-18 | The Broad Institute Inc. | Crystal structure of a crispr-cas system, and uses thereof |
| US11053481B2 (en) | 2013-12-12 | 2021-07-06 | President And Fellows Of Harvard College | Fusions of Cas9 domains and nucleic acid-editing domains |
| EP3540051B1 (en) | 2013-12-12 | 2022-08-17 | The Broad Institute, Inc. | Delivery, use and therapeutic applications of the crispr-cas systems and compositions for hsv and viral diseases and disorders. |
| EP3079726B1 (en) | 2013-12-12 | 2018-12-05 | 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 |
| US20150191744A1 (en) | 2013-12-17 | 2015-07-09 | University Of Massachusetts | Cas9 effector-mediated regulation of transcription, differentiation and gene editing/labeling |
| AU2014368982B2 (en) | 2013-12-19 | 2021-03-25 | Amyris, Inc. | Methods for genomic integration |
| PT3083556T (pt) | 2013-12-19 | 2020-03-05 | Novartis Ag | Lípidos e composições lipídicas para a entrega de agentes ativos |
| WO2015095346A1 (en) | 2013-12-19 | 2015-06-25 | Novartis Ag | Lipids and lipid compositions for the delivery of active agents |
| CA2935032C (en) | 2013-12-26 | 2024-01-23 | The General Hospital Corporation | Multiplex guide rnas |
| US9963689B2 (en) | 2013-12-31 | 2018-05-08 | The Regents Of The University Of California | Cas9 crystals and methods of use thereof |
| AU2015204784B2 (en) | 2014-01-08 | 2021-01-28 | President And Fellows Of Harvard College | RNA-guided gene drives |
| EP3097212A4 (en) | 2014-01-24 | 2017-10-04 | North Carolina State University | Methods and compositions for sequences guiding cas9 targeting |
| US10072066B2 (en) | 2014-02-03 | 2018-09-11 | Sangamo Therapeutics, Inc. | Methods and compositions for treatment of a beta thalessemia |
| US10287590B2 (en) | 2014-02-12 | 2019-05-14 | Dna2.0, Inc. | Methods for generating libraries with co-varying regions of polynuleotides for genome modification |
| WO2015122967A1 (en) | 2014-02-13 | 2015-08-20 | Clontech Laboratories, Inc. | Methods of depleting a target molecule from an initial collection of nucleic acids, and compositions and kits for practicing the same |
| KR20160130392A (ko) | 2014-02-18 | 2016-11-11 | 듀크 유니버시티 | 바이러스 복제의 불활성화를 위한 조성물 및 그의 제조 및 사용 방법 |
| US11186843B2 (en) | 2014-02-27 | 2021-11-30 | Monsanto Technology Llc | Compositions and methods for site directed genomic modification |
| WO2015134812A1 (en) | 2014-03-05 | 2015-09-11 | Editas Medicine, Inc. | Crispr/cas-related methods and compositions for treating usher syndrome and retinitis pigmentosa |
| EP3553176A1 (en) | 2014-03-10 | 2019-10-16 | Editas Medicine, Inc. | Crispr/cas-related methods and compositions for treating leber's congenital amaurosis 10 (lca10) |
| EP3126498A4 (en) | 2014-03-20 | 2017-08-23 | Université Laval | Crispr-based methods and products for increasing frataxin levels and uses thereof |
| PL3122766T3 (pl) | 2014-03-24 | 2021-09-13 | IMMCO Diagnostics, Inc. | Ulepszone wykrywanie i diagnostyka przeciwciał przeciwjądrowych dla układowych i nieukładowych zaburzeń autoimmunologicznych |
| CA2943622A1 (en) | 2014-03-25 | 2015-10-01 | Editas Medicine Inc. | Crispr/cas-related methods and compositions for treating hiv infection and aids |
| EP3122880B1 (en) | 2014-03-26 | 2021-05-05 | Editas Medicine, Inc. | Crispr/cas-related methods and compositions for treating sickle cell disease |
| WO2015148860A1 (en) | 2014-03-26 | 2015-10-01 | Editas Medicine, Inc. | Crispr/cas-related methods and compositions for treating beta-thalassemia |
| WO2015152305A1 (ja) | 2014-03-31 | 2015-10-08 | 株式会社サイエンス・ラスター | 造血細胞の増殖ペプチドおよびその用途 |
| WO2015153791A1 (en) | 2014-04-01 | 2015-10-08 | Editas Medicine, Inc. | Crispr/cas-related methods and compositions for treating herpes simplex virus type 2 (hsv-2) |
| WO2015153789A1 (en) | 2014-04-01 | 2015-10-08 | Editas Medicine, Inc. | Crispr/cas-related methods and compositions for treating herpes simplex virus type 1 (hsv-1) |
| EP3540061A1 (en) | 2014-04-02 | 2019-09-18 | Editas Medicine, Inc. | Crispr/cas-related methods and compositions for treating primary open angle glaucoma |
| WO2015153940A1 (en) | 2014-04-03 | 2015-10-08 | Massachusetts Institute Of Technology | Methods and compositions for the production of guide rna |
| EP3556858A3 (en) | 2014-04-09 | 2020-01-22 | Editas Medicine, Inc. | Crispr/cas-related methods and compositions for treating cystic fibrosis |
| WO2015159068A1 (en) | 2014-04-14 | 2015-10-22 | Nemesis Bioscience Ltd | Therapeutic |
| WO2015161276A2 (en) | 2014-04-18 | 2015-10-22 | Editas Medicine, Inc. | Crispr-cas-related methods, compositions and components for cancer immunotherapy |
| SG10201809290SA (en) | 2014-04-25 | 2019-01-30 | Childrens Medical Ct Corp | Compositions and Methods to Treating Hemoglobinopathies |
| 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 |
| EP3140403A4 (en) | 2014-05-09 | 2017-12-20 | Université Laval | Prevention and treatment of alzheimer's disease by genome editing using the crispr/cas system |
| WO2015173436A1 (en) | 2014-05-16 | 2015-11-19 | Vrije Universiteit Brussel | Genetic correction of myotonic dystrophy type 1 |
| JP2017517256A (ja) | 2014-05-20 | 2017-06-29 | リージェンツ オブ ザ ユニバーシティ オブ ミネソタ | 遺伝子配列を編集する方法 |
| EP3152319A4 (en) | 2014-06-05 | 2017-12-27 | Sangamo BioSciences, Inc. | Methods and compositions for nuclease design |
| BR112016028564A2 (pt) | 2014-06-06 | 2018-01-30 | Regeneron Pharma | método para modificar um locus-alvo em uma célula. |
| WO2015191693A2 (en) | 2014-06-10 | 2015-12-17 | Massachusetts Institute Of Technology | Method for gene editing |
| WO2015191911A2 (en) | 2014-06-12 | 2015-12-17 | Clontech Laboratories, Inc. | Protein enriched microvesicles and methods of making and using the same |
| MX384887B (es) | 2014-06-23 | 2025-03-14 | Regeneron Pharma | Ensamblaje de adn mediado por nucleasa. |
| WO2015200555A2 (en) | 2014-06-25 | 2015-12-30 | Caribou Biosciences, Inc. | Rna modification to engineer cas9 activity |
| US20150376586A1 (en) | 2014-06-25 | 2015-12-31 | Caribou Biosciences, Inc. | RNA Modification to Engineer Cas9 Activity |
| SG10201911411YA (en) | 2014-06-26 | 2020-02-27 | Regeneron Pharma | Methods and compositions for targeted genetic modifications and methods of use |
| US10017770B2 (en) | 2014-07-03 | 2018-07-10 | Ut-Battelle, Llc | TNT cloning system |
| BR112017000621B1 (pt) | 2014-07-11 | 2024-03-12 | Pioneer Hi-Bred International, Inc | Método para melhorar um traço agronômico de uma planta de milho ou de soja |
| US11254933B2 (en) | 2014-07-14 | 2022-02-22 | The Regents Of The University Of California | CRISPR/Cas transcriptional modulation |
| US10975406B2 (en) | 2014-07-18 | 2021-04-13 | Massachusetts Institute Of Technology | Directed endonucleases for repeatable nucleic acid cleavage |
| AU2015298571B2 (en) | 2014-07-30 | 2020-09-03 | President And Fellows Of Harvard College | Cas9 proteins including ligand-dependent inteins |
| KR102500531B1 (ko) | 2014-09-04 | 2023-02-17 | 메모리얼 슬로안 케터링 캔서 센터 | 헤모글로빈병증 치료용 글로빈 유전자 치료법 |
| CN106795488B (zh) | 2014-09-16 | 2021-03-30 | 桑格摩治疗股份有限公司 | 用于造血干细胞中核酸酶介导的基因组工程化和校正的方法和组合物 |
| WO2016049258A2 (en) | 2014-09-25 | 2016-03-31 | The Broad Institute Inc. | Functional screening with optimized functional crispr-cas systems |
| EP3204496A1 (en) | 2014-10-10 | 2017-08-16 | Editas Medicine, Inc. | Compositions and methods for promoting homology directed repair |
| AU2015342749B2 (en) | 2014-11-07 | 2022-01-27 | Editas Medicine, Inc. | Methods for improving CRISPR/Cas-mediated genome-editing |
| 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) |
| EP3237615B2 (en) | 2014-12-24 | 2023-07-26 | The Broad Institute, Inc. | Crispr having or associated with destabilization domains |
| WO2016103233A2 (en) * | 2014-12-24 | 2016-06-30 | Dana-Farber Cancer Institute, Inc. | Systems and methods for genome modification and regulation |
| 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 |
| EP3247366A4 (en) | 2015-01-21 | 2018-10-31 | Sangamo Therapeutics, Inc. | Methods and compositions for identification of highly specific nucleases |
| JP6734283B2 (ja) | 2015-01-21 | 2020-08-05 | フレッド ハッチンソン キャンサー リサーチ センター | 遺伝子治療用ポイントオブケア及び／又はポータブルプラットフォーム |
| EP3247409B1 (en) | 2015-01-21 | 2020-11-04 | Cornell University | Viral vectors for prophylaxis and therapy of hemoglobinopathies |
| EP3256487A4 (en) | 2015-02-09 | 2018-07-18 | Duke University | Compositions and methods for epigenome editing |
| EP3256170B1 (en) | 2015-02-13 | 2020-09-23 | University of Massachusetts | Compositions and methods for transient delivery of nucleases |
| AU2016225178B2 (en) | 2015-02-23 | 2022-05-05 | Crispr Therapeutics Ag | Materials and methods for treatment of hemoglobinopathies |
| US20180271891A1 (en) | 2015-03-11 | 2018-09-27 | The Broad Institute Inc. | Selective treatment of prmt5 dependent cancer |
| WO2016154596A1 (en) | 2015-03-25 | 2016-09-29 | Editas Medicine, Inc. | Crispr/cas-related methods, compositions and components |
| EP3274453B1 (en) | 2015-03-26 | 2021-01-27 | Editas Medicine, Inc. | Crispr/cas-mediated gene conversion |
| ES2764457T3 (es) | 2015-03-31 | 2020-06-03 | Glycotope Gmbh | Vectores de expresión eucariotas que incluyen elementos reglamentarios de los grupos de genes de globina |
| ES2884838T3 (es) | 2015-04-06 | 2021-12-13 | Univ Leland Stanford Junior | ARN guía químicamente modificados para la regulación génica mediada por CRISPR/CAS |
| JP7288302B2 (ja) | 2015-05-08 | 2023-06-07 | ザ チルドレンズ メディカル センター コーポレーション | 胎児型ヘモグロビン再誘導のための、ｂｃｌ１１ａエンハンサー機能性領域を標的とする方法 |
| WO2016182893A1 (en) | 2015-05-08 | 2016-11-17 | Teh Broad Institute Inc. | Functional genomics using crispr-cas systems for saturating mutagenesis of non-coding elements, compositions, methods, libraries and applications thereof |
| EP3294896A1 (en) | 2015-05-11 | 2018-03-21 | Editas Medicine, Inc. | Optimized crispr/cas9 systems and methods for gene editing in stem cells |
| KR20170141217A (ko) | 2015-05-12 | 2017-12-22 | 상가모 테라퓨틱스, 인코포레이티드 | 유전자 발현의 뉴클레아제-매개된 조절 |
| WO2016201272A1 (en) | 2015-06-12 | 2016-12-15 | King Abdulaziz City For Science And Technology | Method of diagnosing patients with conditions caused by mendelian mutations |
| WO2016205703A1 (en) | 2015-06-17 | 2016-12-22 | The Uab Research Foundation | Crispr/cas9 complex for genomic editing |
| US9957501B2 (en) | 2015-06-18 | 2018-05-01 | Sangamo Therapeutics, Inc. | Nuclease-mediated regulation of gene expression |
| WO2017053729A1 (en) | 2015-09-25 | 2017-03-30 | The Board Of Trustees Of The Leland Stanford Junior University | Nuclease-mediated genome editing of primary cells and enrichment thereof |
| WO2017059241A1 (en) | 2015-10-02 | 2017-04-06 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Lentiviral protein delivery system for rna-guided genome editing |
| WO2017077394A2 (en) | 2015-11-04 | 2017-05-11 | Crispr Therapeutics Ag | Materials and methods for treatment of hemoglobinopathies |
| EA201891532A1 (ru) | 2015-12-28 | 2019-01-31 | Новартис Аг | Композиции и способы лечения гемоглобинопатий |
| IL313038A (en) * | 2016-03-14 | 2024-07-01 | Editas Medicine Inc | Methods and preparations related to CRISPR/CAS - for the treatment of diseases in the hemoglobin cell |
| SG11201809144XA (en) | 2016-04-18 | 2018-11-29 | Crispr Therapeutics Ag | Materials and methods for treatment of hemoglobinopathies |
| WO2017191503A1 (en) | 2016-05-05 | 2017-11-09 | Crispr Therapeutics Ag | Materials and methods for treatment of hemoglobinopathies |
| EP3471743B1 (en) | 2016-06-17 | 2025-08-06 | Fred Hutchinson Cancer Center | Strategies to assess and/or produce cell populations with predictive engraftment potential |
| WO2018009506A1 (en) | 2016-07-07 | 2018-01-11 | St. Jude Children's Research Hospital | Erythroid-specific promoter and method of use thereof |
| CN109689865A (zh) | 2016-07-25 | 2019-04-26 | 蓝鸟生物公司 | Bcl11a归巢核酸内切酶变体、组合物和使用方法 |
| WO2018035423A1 (en) | 2016-08-19 | 2018-02-22 | Bluebird Bio, Inc. | Genome editing enhancers |
| SG11201901531TA (en) | 2016-08-24 | 2019-03-28 | Sangamo Therapeutics Inc | Regulation of gene expression using engineered nucleases |
| US10975393B2 (en) | 2016-08-24 | 2021-04-13 | Sangamo Therapeutics, Inc. | Engineered target specific nucleases |
| JP2019532672A (ja) | 2016-09-28 | 2019-11-14 | ノバルティス アーゲー | 多孔質膜系巨大分子送達システム |
| 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 |
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