JP2014530603A - Ｈｉｖ感染を制御するための方法および組成物 - Google Patents
Ｈｉｖ感染を制御するための方法および組成物 Download PDFInfo
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| US8895264B2 (en) * | 2011-10-27 | 2014-11-25 | Sangamo Biosciences, Inc. | Methods and compositions for modification of the HPRT locus |
| SG10201707569YA (en) | 2012-12-12 | 2017-10-30 | Broad Inst Inc | Delivery, Engineering and Optimization of Systems, Methods and Compositions for Sequence Manipulation and Therapeutic Applications |
| 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 |
| 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 |
| WO2014204727A1 (en) | 2013-06-17 | 2014-12-24 | The Broad Institute Inc. | Functional genomics using crispr-cas systems, compositions methods, screens and applications thereof |
| WO2014204725A1 (en) | 2013-06-17 | 2014-12-24 | The Broad Institute Inc. | Optimized crispr-cas double nickase systems, methods and compositions for sequence manipulation |
| JP6738728B2 (ja) | 2013-06-17 | 2020-08-19 | ザ・ブロード・インスティテュート・インコーポレイテッド | 肝臓ターゲティングおよび治療のためのＣＲＩＳＰＲ−Ｃａｓ系、ベクターおよび組成物の送達および使用 |
| BR112015031611A2 (pt) | 2013-06-17 | 2017-12-12 | Massachusetts Inst Technology | aplicação, manipulação e otimização de sistemas, métodos e composições para direcionamento e modelação de doenças e distúrbios de células pós-mitóticas |
| AU2014281031B2 (en) | 2013-06-17 | 2020-05-21 | Massachusetts Institute Of Technology | Delivery, use and therapeutic applications of the CRISPR-Cas systems and compositions for targeting disorders and diseases using viral components |
| WO2014204724A1 (en) | 2013-06-17 | 2014-12-24 | The Broad Institute Inc. | Delivery, engineering and optimization of tandem guide systems, methods and compositions for sequence manipulation |
| US20160298096A1 (en) * | 2013-11-18 | 2016-10-13 | Crispr Therapeutics Ag | Crispr-cas system materials and methods |
| 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 |
| JP6793547B2 (ja) | 2013-12-12 | 2020-12-02 | ザ・ブロード・インスティテュート・インコーポレイテッド | 最適化機能ＣＲＩＳＰＲ−Ｃａｓ系による配列操作のための系、方法および組成物 |
| JP2017501149A (ja) | 2013-12-12 | 2017-01-12 | ザ・ブロード・インスティテュート・インコーポレイテッド | 粒子送達構成成分を用いた障害及び疾患の標的化のためのｃｒｉｓｐｒ−ｃａｓ系及び組成物の送達、使用及び治療適用 |
| WO2015089364A1 (en) | 2013-12-12 | 2015-06-18 | The Broad Institute Inc. | Crystal structure of a crispr-cas system, and uses thereof |
| JP2017527256A (ja) | 2013-12-12 | 2017-09-21 | ザ・ブロード・インスティテュート・インコーポレイテッド | ＨＢＶ及びウイルス性疾患及び障害のためのＣＲＩＳＰＲ−Ｃａｓ系及び組成物の送達、使用及び治療適用 |
| MX2016007325A (es) | 2013-12-12 | 2017-07-19 | Broad Inst Inc | Composiciones y metodos de uso de sistemas crispr-cas en desordenes debidos a repeticion de nucleotidos. |
| MX374529B (es) | 2013-12-12 | 2025-03-06 | Broad Inst Inc | Suministro, uso y aplicaciones terapeuticas de sistemas y composiciones crispr-cas para edicion del genoma. |
| WO2016014837A1 (en) * | 2014-07-25 | 2016-01-28 | Sangamo Biosciences, Inc. | Gene editing for hiv gene therapy |
| EP3985115A1 (en) | 2014-12-12 | 2022-04-20 | The Broad Institute, Inc. | Protected guide rnas (pgrnas) |
| EP3237615B2 (en) | 2014-12-24 | 2023-07-26 | The Broad Institute, Inc. | Crispr having or associated with destabilization domains |
| US10059940B2 (en) * | 2015-01-27 | 2018-08-28 | Minghong Zhong | Chemically ligated RNAs for CRISPR/Cas9-lgRNA complexes as antiviral therapeutic agents |
| 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 |
| CA2989830A1 (en) | 2015-06-18 | 2016-12-22 | The Broad Institute, Inc. | Crispr enzyme mutations reducing off-target effects |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2009502170A (ja) * | 2005-07-26 | 2009-01-29 | サンガモ バイオサイエンシズ インコーポレイテッド | 外来核酸配列の標的化された組込み及び発現 |
Family Cites Families (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1352960A1 (en) * | 2002-04-12 | 2003-10-15 | Viruvation B.V. | Antiviral therapy on the basis of RNA interference |
| WO2007014181A2 (en) * | 2005-07-25 | 2007-02-01 | Johns Hopkins University | Site-specific modification of the human genome using custom-designed zinc finger nucleases |
| US20080003681A1 (en) * | 2006-06-28 | 2008-01-03 | Mahalaxmi Gita Bangera | Methods for altering cellular susceptibility to infection |
| US8563314B2 (en) * | 2007-09-27 | 2013-10-22 | Sangamo Biosciences, Inc. | Methods and compositions for modulating PD1 |
| AU2009257663B2 (en) * | 2008-06-09 | 2014-06-26 | New York Medical College | Compositions comprising cardiac stem cells overexpressing specific microRNA and methods of their use in repairing damaged myocardium |
| US8871905B2 (en) * | 2009-03-20 | 2014-10-28 | Sangamo Biosciences, Inc. | Modification of CXCR4 using engineered zinc finger proteins |
| EP2462230B1 (en) * | 2009-08-03 | 2015-07-15 | Recombinetics, Inc. | Methods and compositions for targeted gene modification |
| CN102071219B (zh) * | 2010-11-05 | 2014-03-12 | 冯小荣 | 改腺载体及其在艾滋病预防和治疗药物中的应用 |
-
2012
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- 2012-10-04 HK HK15101108.0A patent/HK1200491A1/xx unknown
- 2012-10-04 EP EP12838704.0A patent/EP2764102A4/en not_active Withdrawn
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-
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- 2015-05-28 US US14/724,250 patent/US20150267223A1/en not_active Abandoned
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2009502170A (ja) * | 2005-07-26 | 2009-01-29 | サンガモ バイオサイエンシズ インコーポレイテッド | 外来核酸配列の標的化された組込み及び発現 |
Non-Patent Citations (3)
| Title |
|---|
| JPN6016020895; Ｎａｔ． Ｂｉｏｔｅｃｈｎｏｌ． Ｖｏｌ． ２８， ｎｏ． ８, 2010, ｐ． ８３９-８４７ * |
| JPN6016020897; Ｍｏｌ． Ｔｈｅｒ． Ｖｏｌ． １２， Ｎｏ． ５, 2005, ｐ． ９００-９０９ * |
| JPN6016020900; Ｎａｔ． Ｍｅｔｈｏｄｓ Ｖｏｌ． ８， Ｎｏ． １０, 20110821, ｐ． ８６１-８６９ * |
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| WO2013052681A1 (en) | 2013-04-11 |
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| HK1200491A1 (en) | 2015-08-07 |
| US20150267223A1 (en) | 2015-09-24 |
| EP2764102A1 (en) | 2014-08-13 |
| EP2764102A4 (en) | 2015-06-10 |
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