IL294535A - Zinc finger protein transcription factors for repressing tau expression - Google Patents
Zinc finger protein transcription factors for repressing tau expressionInfo
- Publication number
- IL294535A IL294535A IL294535A IL29453522A IL294535A IL 294535 A IL294535 A IL 294535A IL 294535 A IL294535 A IL 294535A IL 29453522 A IL29453522 A IL 29453522A IL 294535 A IL294535 A IL 294535A
- Authority
- IL
- Israel
- Prior art keywords
- zfp
- fusion protein
- dna
- cell
- domain
- Prior art date
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|---|---|---|---|---|
| US6140466A (en) | 1994-01-18 | 2000-10-31 | The Scripps Research Institute | Zinc finger protein derivatives and methods therefor |
| JP4012243B2 (ja) | 1994-01-18 | 2007-11-21 | ザ スクリップス リサーチ インスティチュート | 亜鉛フィンガータンパク質誘導体およびそのための方法 |
| GB9824544D0 (en) | 1998-11-09 | 1999-01-06 | Medical Res Council | Screening system |
| CA2196419C (en) | 1994-08-20 | 2007-08-21 | Yen Choo | Improvements in or relating to binding proteins for recognition of dna |
| GB9710807D0 (en) | 1997-05-23 | 1997-07-23 | Medical Res Council | Nucleic acid binding proteins |
| GB9710809D0 (en) | 1997-05-23 | 1997-07-23 | Medical Res Council | Nucleic acid binding proteins |
| DE69942334D1 (de) | 1998-03-02 | 2010-06-17 | Massachusetts Inst Technology | Poly-zinkfinger-proteine mit verbesserten linkern |
| WO2001053480A1 (en) | 2000-01-24 | 2001-07-26 | Sangamo Biosciences, Inc. | Nucleic acid binding polypeptides characterized by flexible linkers connected nucleic acid binding modules |
| US20020061512A1 (en) | 2000-02-18 | 2002-05-23 | Kim Jin-Soo | Zinc finger domains and methods of identifying same |
| AU2001263155A1 (en) | 2000-05-16 | 2001-11-26 | Massachusetts Institute Of Technology | Methods and compositions for interaction trap assays |
| JP2002060786A (ja) | 2000-08-23 | 2002-02-26 | Kao Corp | 硬質表面用殺菌防汚剤 |
| GB0108491D0 (en) | 2001-04-04 | 2001-05-23 | Gendaq Ltd | Engineering zinc fingers |
| US20040224385A1 (en) | 2001-08-20 | 2004-11-11 | Barbas Carlos F | Zinc finger binding domains for cnn |
| CA2725773C (en) | 2008-05-28 | 2017-12-05 | Sangamo Biosciences, Inc. | Compositions for linking dna-binding domains and cleavage domains |
| EP2566972B1 (en) | 2010-05-03 | 2020-01-15 | Sangamo Therapeutics, Inc. | Compositions for linking zinc finger modules |
| CA2920899C (en) | 2013-08-28 | 2023-02-28 | Sangamo Biosciences, Inc. | Compositions for linking dna-binding domains and cleavage domains |
| EP3929279A1 (en) | 2014-03-18 | 2021-12-29 | Sangamo Therapeutics, Inc. | Methods and compositions for regulation of zinc finger protein expression |
| WO2017011556A1 (en) * | 2015-07-13 | 2017-01-19 | The General Hospital Corporation | Rare phosphorylated high molecular weight (hmw) tau species that are involved in neuronal uptake and propagation and applications thereof |
| JP7012650B2 (ja) | 2016-02-02 | 2022-01-28 | サンガモ セラピューティクス， インコーポレイテッド | Ｄｎａ結合ドメインと切断ドメインとを連結するための組成物 |
| IL264792B2 (en) | 2016-08-24 | 2023-10-01 | Sangamo Therapeutics Inc | Engineered target-specific zinc-finger nucleases |
| CN110214184B (zh) * | 2016-12-01 | 2024-07-02 | 桑格摩生物治疗股份有限公司 | τ蛋白调节剂以及用于其递送的方法和组合物 |
| KR20210069692A (ko) | 2018-10-02 | 2021-06-11 | 상가모 테라퓨틱스, 인코포레이티드 | 조작된 유전자 조정제 |
| IL326834A (en) | 2018-10-02 | 2026-04-01 | Sangamo Therapeutics Inc | Artificial zinc finger protein transcription factors repressing mapt expression for the prevention and/or treatment of tauopathies |
-
2021
- 2021-01-22 TW TW110102602A patent/TW202134288A/zh unknown
- 2021-01-22 US US17/791,395 patent/US20230242602A1/en active Pending
- 2021-01-22 UY UY0001039036A patent/UY39036A/es not_active Application Discontinuation
- 2021-01-22 BR BR112022014160A patent/BR112022014160A2/pt not_active Application Discontinuation
- 2021-01-22 AU AU2021209699A patent/AU2021209699A1/en active Pending
- 2021-01-22 MX MX2022008953A patent/MX2022008953A/es unknown
- 2021-01-22 AR ARP210100163A patent/AR121118A1/es unknown
- 2021-01-22 EP EP21706102.7A patent/EP4093754A1/en active Pending
- 2021-01-22 CA CA3168805A patent/CA3168805A1/en active Pending
- 2021-01-22 IL IL294535A patent/IL294535A/en unknown
- 2021-01-22 KR KR1020227028167A patent/KR20220131273A/ko active Pending
- 2021-01-22 CN CN202180010601.9A patent/CN115210251A/zh active Pending
- 2021-01-22 JP JP2022544353A patent/JP2023511908A/ja not_active Ceased
- 2021-01-22 WO PCT/US2021/014780 patent/WO2021151012A1/en not_active Ceased
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| Publication number | Publication date |
|---|---|
| UY39036A (es) | 2021-08-31 |
| BR112022014160A2 (pt) | 2022-09-13 |
| JP2023511908A (ja) | 2023-03-23 |
| MX2022008953A (es) | 2022-08-15 |
| WO2021151012A1 (en) | 2021-07-29 |
| CN115210251A (zh) | 2022-10-18 |
| KR20220131273A (ko) | 2022-09-27 |
| EP4093754A1 (en) | 2022-11-30 |
| AR121118A1 (es) | 2022-04-20 |
| US20230242602A1 (en) | 2023-08-03 |
| AU2021209699A1 (en) | 2022-07-21 |
| CA3168805A1 (en) | 2021-07-29 |
| TW202134288A (zh) | 2021-09-16 |
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