ES2716867T3 - Endonucleasa de asentamiento LAGLIDADG que escinde el gen de receptor de células T alfa y usos de la misma - Google Patents
Endonucleasa de asentamiento LAGLIDADG que escinde el gen de receptor de células T alfa y usos de la misma Download PDFInfo
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- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/43—Enzymes; Proenzymes; Derivatives thereof
- A61K38/46—Hydrolases (3)
- A61K38/465—Hydrolases (3) acting on ester bonds (3.1), e.g. lipases, ribonucleases
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K48/00—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
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| PCT/EP2014/061189 WO2014191527A1 (en) | 2013-05-31 | 2014-05-28 | A laglidadg homing endonuclease cleaving the t cell receptor alpha gene and uses thereof |
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Families Citing this family (78)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP5996630B2 (ja) * | 2011-04-05 | 2016-09-21 | セレクティスＣｅｌｌｅｃｔｉｓ | コンパクトｔａｌｅ−ヌクレアーゼを作製する方法及びその使用 |
| 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 |
| US10704021B2 (en) | 2012-03-15 | 2020-07-07 | Flodesign Sonics, Inc. | Acoustic perfusion devices |
| US20150044192A1 (en) | 2013-08-09 | 2015-02-12 | President And Fellows Of Harvard College | Methods for identifying a target site of a cas9 nuclease |
| US9359599B2 (en) | 2013-08-22 | 2016-06-07 | President And Fellows Of Harvard College | Engineered transcription activator-like effector (TALE) domains and uses thereof |
| US9737604B2 (en) | 2013-09-06 | 2017-08-22 | President And Fellows Of Harvard College | Use of cationic lipids to deliver CAS9 |
| US9228207B2 (en) | 2013-09-06 | 2016-01-05 | President And Fellows Of Harvard College | Switchable gRNAs comprising aptamers |
| US9322037B2 (en) | 2013-09-06 | 2016-04-26 | President And Fellows Of Harvard College | Cas9-FokI fusion proteins and uses thereof |
| PT3066201T (pt) | 2013-11-07 | 2018-06-04 | Massachusetts Inst Technology | Métodos e composições relacionadas com crispr com arng reguladores |
| US9068179B1 (en) | 2013-12-12 | 2015-06-30 | President And Fellows Of Harvard College | Methods for correcting presenilin point mutations |
| WO2015105955A1 (en) | 2014-01-08 | 2015-07-16 | Flodesign Sonics, Inc. | Acoustophoresis device with dual acoustophoretic chamber |
| US10077453B2 (en) | 2014-07-30 | 2018-09-18 | President And Fellows Of Harvard College | CAS9 proteins including ligand-dependent inteins |
| US11708572B2 (en) | 2015-04-29 | 2023-07-25 | Flodesign Sonics, Inc. | Acoustic cell separation techniques and processes |
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| EP3365356B1 (en) | 2015-10-23 | 2023-06-28 | President and Fellows of Harvard College | Nucleobase editors and uses thereof |
| SG10202109655VA (en) | 2015-12-04 | 2021-10-28 | Novartis Ag | Compositions and methods for immunooncology |
| EP3426690A4 (en) * | 2016-03-11 | 2019-10-09 | Bluebird Bio, Inc. | GENOMEDITIZED IMMUNEFFECTOR CELLS |
| EP4166161A1 (en) * | 2016-04-14 | 2023-04-19 | Fred Hutchinson Cancer Center | Compositions and methods to program therapeutic cells using targeted nucleic acid nanocarriers |
| US10188749B2 (en) | 2016-04-14 | 2019-01-29 | Fred Hutchinson Cancer Research Center | Compositions and methods to program therapeutic cells using targeted nucleic acid nanocarriers |
| US11214789B2 (en) | 2016-05-03 | 2022-01-04 | Flodesign Sonics, Inc. | Concentration and washing of particles with acoustics |
| CA3031785A1 (en) * | 2016-07-25 | 2018-02-01 | Bluebird Bio, Inc. | Bcl11a homing endonuclease variants, compositions, and methods of use |
| 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 |
| EP3500696A4 (en) * | 2016-08-16 | 2020-04-08 | Bluebird Bio, Inc. | VARIANTS OF IL-10 ALPHA RECEPTOR HOMING ENDONUCLEASE, COMPOSITIONS AND METHODS OF USE |
| WO2018039333A1 (en) * | 2016-08-23 | 2018-03-01 | Bluebird Bio, Inc. | Tim3 homing endonuclease variants, compositions, and methods of use |
| WO2018039438A1 (en) | 2016-08-24 | 2018-03-01 | President And Fellows Of Harvard College | Incorporation of unnatural amino acids into proteins using base editing |
| KR102622910B1 (ko) * | 2016-09-08 | 2024-01-10 | 2세븐티 바이오, 인코포레이티드 | Pd-1 호밍 엔도뉴클레아제 변이체, 조성물 및 사용 방법 |
| US11591582B2 (en) | 2016-10-11 | 2023-02-28 | 2Seventy Bio, Inc. | TCRα homing endonuclease variants |
| EP3526320A1 (en) | 2016-10-14 | 2019-08-21 | President and Fellows of Harvard College | Aav delivery of nucleobase editors |
| WO2018075541A1 (en) * | 2016-10-17 | 2018-04-26 | Bluebird Bio, Inc. | TGFβR2 ENDONUCLEASE VARIANTS, COMPOSITIONS, AND METHODS OF USE |
| WO2018073393A2 (en) | 2016-10-19 | 2018-04-26 | Cellectis | Tal-effector nuclease (talen) -modified allogenic cells suitable for therapy |
| BR112019011277A2 (pt) | 2016-12-02 | 2019-10-22 | University Of Southern California | polinucleotídeo, sistema de expressão recombinante, vetor, polipeptídeo, célula recombinante, polipeptídeo de receptor imune sintético isolado ou heterodímero de polipeptídeo, célula efetora imune ou célula-tronco, população de células imunes ou efetoras, métodos de fabricação de uma célula efetora imune que expressa sir, de geração de uma população de células modificadas por rna, de fornecimento de imunidade antidoença e de tratamento ou prevenção de uma doença, composição, uso ou método, kit, e, sequência de aminoácidos. |
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| EP3565535A4 (en) | 2017-01-05 | 2020-12-30 | Fred Hutchinson Cancer Research Center | SYSTEMS AND METHODS FOR IMPROVING THE EFFECTIVENESS OF A VACCINE |
| WO2018165631A1 (en) | 2017-03-09 | 2018-09-13 | President And Fellows Of Harvard College | Cancer vaccine |
| WO2018165504A1 (en) | 2017-03-09 | 2018-09-13 | President And Fellows Of Harvard College | Suppression of pain by gene editing |
| KR20190127797A (ko) | 2017-03-10 | 2019-11-13 | 프레지던트 앤드 펠로우즈 오브 하바드 칼리지 | 시토신에서 구아닌으로의 염기 편집제 |
| JP2020513832A (ja) | 2017-03-22 | 2020-05-21 | ノバルティス アーゲー | 免疫腫瘍学のための組成物および方法 |
| KR20240116572A (ko) | 2017-03-23 | 2024-07-29 | 프레지던트 앤드 펠로우즈 오브 하바드 칼리지 | 핵산 프로그램가능한 dna 결합 단백질을 포함하는 핵염기 편집제 |
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| 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 |
| MA48797A (fr) | 2017-05-25 | 2020-04-08 | Bluebird Bio Inc | Variants de l'endonucléase cblb , compositions et procédés d'utilisation |
| US11053484B2 (en) | 2017-06-30 | 2021-07-06 | Precision Biosciences, Inc. | Genetically-modified T cells comprising a modified intron in the T cell receptor alpha gene |
| WO2019023680A1 (en) | 2017-07-28 | 2019-01-31 | President And Fellows Of Harvard College | METHODS AND COMPOSITIONS FOR EVOLUTION OF BASIC EDITORS USING PHAGE-ASSISTED CONTINUOUS EVOLUTION (PACE) |
| EP3676376B1 (en) | 2017-08-30 | 2025-01-15 | President and Fellows of Harvard College | High efficiency base editors comprising gam |
| WO2019070974A1 (en) * | 2017-10-04 | 2019-04-11 | Bluebird Bio, Inc. | PCSK9 ENDONUCLEASE VARIANTS, COMPOSITIONS AND METHODS OF USE |
| JP7207661B2 (ja) * | 2017-10-10 | 2023-01-18 | 国立大学法人広島大学 | Ｐｌａｔｉｎｕｍ ＴＡＬＥＮを用いたＴ細胞受容体の完全置換技術 |
| WO2019073965A1 (ja) | 2017-10-10 | 2019-04-18 | 国立大学法人広島大学 | エフェクターＴ細胞（Ｔｅｆｆ）抗原受容体を用いた抗原特異的制御性Ｔ細胞（Ｔｒｅｇ）の作出技術 |
| 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 |
| BR112020009889A2 (pt) | 2017-12-14 | 2020-11-03 | Flodesign Sonics, Inc. | acionador e controlador de transdutor acústico |
| WO2019118949A1 (en) | 2017-12-15 | 2019-06-20 | The Broad Institute, Inc. | Systems and methods for predicting repair outcomes in genetic engineering |
| WO2019126555A1 (en) * | 2017-12-20 | 2019-06-27 | Bluebird Bio, Inc. | Ctla4 homing endonuclease variants, compositions, and methods of use |
| IL304025A (en) | 2018-04-12 | 2023-08-01 | Prec Biosciences Inc | Optimized engineered nucleases with specificity for the human T cell receptor alpha constant region gene |
| US12157760B2 (en) | 2018-05-23 | 2024-12-03 | The Broad Institute, Inc. | Base editors and uses thereof |
| EP3806903B1 (en) | 2018-06-14 | 2024-02-14 | 2seventy bio, Inc. | Cd79a chimeric antigen receptors |
| WO2020072059A1 (en) | 2018-10-04 | 2020-04-09 | Bluebird Bio, Inc. | Cblb endonuclease variants, compositions, and methods of use |
| US12331320B2 (en) | 2018-10-10 | 2025-06-17 | The Research Foundation For The State University Of New York | Genome edited cancer cell vaccines |
| US12281338B2 (en) | 2018-10-29 | 2025-04-22 | The Broad Institute, Inc. | Nucleobase editors comprising GeoCas9 and uses thereof |
| KR20210102925A (ko) | 2018-12-10 | 2021-08-20 | 블루버드 바이오, 인코포레이티드. | 호밍 엔도뉴클레아제 변이체 |
| 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. |
| CN116200342A (zh) | 2019-04-03 | 2023-06-02 | 精密生物科学公司 | 包含microRNA适应的shRNA（shRNAmiR）的遗传修饰的免疫细胞 |
| EP3956349A1 (en) | 2019-04-17 | 2022-02-23 | The Broad Institute, Inc. | Adenine base editors with reduced off-target effects |
| WO2021016608A1 (en) | 2019-07-25 | 2021-01-28 | Precision Biosciences, Inc. | Compositions and methods for sequential stacking of nucleic acid sequences into a genomic locus |
| EP4017526A1 (en) | 2019-08-20 | 2022-06-29 | Precision BioSciences, Inc. | Lymphodepletion dosing regimens for cellular immunotherapies |
| US12435330B2 (en) | 2019-10-10 | 2025-10-07 | The Broad Institute, Inc. | Methods and compositions for prime editing RNA |
| WO2021087305A1 (en) | 2019-10-30 | 2021-05-06 | Precision Biosciences, Inc. | Cd20 chimeric antigen receptors and methods of use for immunotherapy |
| 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. |
| WO2022035793A1 (en) | 2020-08-10 | 2022-02-17 | Precision Biosciences, Inc. | Antibodies and fragments specific for b-cell maturation antigen and uses thereof |
| US20240336904A1 (en) * | 2020-12-21 | 2024-10-10 | 2Seventy Bio, Inc. | Compositions and methods for site-directed mutagenesis |
| WO2022165111A1 (en) | 2021-01-28 | 2022-08-04 | Precision Biosciences, Inc. | Modulation of tgf beta signaling in genetically-modified eukaryotic cells |
| EP4426832A1 (en) | 2021-11-03 | 2024-09-11 | The J. David Gladstone Institutes, A Testamentary Trust Established under The Will of J. David Gladstone | Precise genome editing using retrons |
| WO2023081767A1 (en) | 2021-11-05 | 2023-05-11 | Precision Biosciences, Inc. | Methods for immunotherapy |
| MX2024006051A (es) | 2021-11-23 | 2024-06-26 | Cellectis Sa | Nuevos andamios de proteinas tale con relaciones de actividad en objetivo/fuera de objetivo mejoradas. |
| WO2023141602A2 (en) | 2022-01-21 | 2023-07-27 | Renagade Therapeutics Management Inc. | Engineered retrons and methods of use |
| WO2024044723A1 (en) | 2022-08-25 | 2024-02-29 | Renagade Therapeutics Management Inc. | Engineered retrons and methods of use |
| AU2024206812A1 (en) | 2023-01-05 | 2025-08-14 | Precision Biosciences, Inc. | Optimized engineered meganucleases having specificity for the human t cell receptor alpha constant region gene |
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| US8956828B2 (en) * | 2009-11-10 | 2015-02-17 | Sangamo Biosciences, Inc. | Targeted disruption of T cell receptor genes using engineered zinc finger protein nucleases |
| US20140148361A1 (en) | 2010-06-07 | 2014-05-29 | Barry L. Stoddard | Generation and Expression of Engineered I-ONUI Endonuclease and Its Homologues and Uses Thereof |
| JP5996630B2 (ja) * | 2011-04-05 | 2016-09-21 | セレクティスＣｅｌｌｅｃｔｉｓ | コンパクトｔａｌｅ−ヌクレアーゼを作製する方法及びその使用 |
| WO2013009525A1 (en) * | 2011-07-08 | 2013-01-17 | Cellectis S.A. | Method for increasing the efficiency of double-strand break-induced mutagenssis |
| US20130210151A1 (en) * | 2011-11-07 | 2013-08-15 | University Of Western Ontario | Endonuclease for genome editing |
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