CA2607668A1 - Rnai modulation of the rho-a gene and uses thereof - Google Patents
Rnai modulation of the rho-a gene and uses thereof Download PDFInfo
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- CA2607668A1 CA2607668A1 CA002607668A CA2607668A CA2607668A1 CA 2607668 A1 CA2607668 A1 CA 2607668A1 CA 002607668 A CA002607668 A CA 002607668A CA 2607668 A CA2607668 A CA 2607668A CA 2607668 A1 CA2607668 A1 CA 2607668A1
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- rtl
- irna agent
- nucleotide
- rhoa
- agent
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| AU2008306455C1 (en) * | 2007-10-03 | 2014-04-17 | Quark Pharmaceuticals, Inc. | Novel siRNA structures |
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| ES2804764T3 (es) | 2009-06-01 | 2021-02-09 | Halo Bio Rnai Therapeutics Inc | Polinucleótidos para la interferencia de ARN multivalente, composiciones y métodos de uso de los mismos |
| US20110020359A1 (en) * | 2009-07-24 | 2011-01-27 | California Institute Of Technology | Methods and compositions for treating neuronal damage or degeneration |
| WO2011021221A2 (en) * | 2009-08-17 | 2011-02-24 | Reliance Life Sciences Pvt. Ltd. | Compositions for spinal cord injury |
| US8901097B2 (en) | 2009-11-08 | 2014-12-02 | Quark Pharmaceuticals, Inc. | Methods for delivery of siRNA to the spinal cord and therapies arising therefrom |
| CN103097534B (zh) * | 2010-06-24 | 2017-07-28 | 夸克制药公司 | 针对rhoa的双链rna化合物及其用途 |
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| US6410323B1 (en) * | 1999-08-31 | 2002-06-25 | Isis Pharmaceuticals, Inc. | Antisense modulation of human Rho family gene expression |
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| US20070026394A1 (en) * | 2000-02-11 | 2007-02-01 | Lawrence Blatt | Modulation of gene expression associated with inflammation proliferation and neurite outgrowth using nucleic acid based technologies |
| US20050020525A1 (en) * | 2002-02-20 | 2005-01-27 | Sirna Therapeutics, Inc. | RNA interference mediated inhibition of gene expression using chemically modified short interfering nucleic acid (siNA) |
| US6945969B1 (en) * | 2000-03-31 | 2005-09-20 | Medtronic, Inc. | Catheter for target specific drug delivery |
| US6551290B1 (en) * | 2000-03-31 | 2003-04-22 | Medtronic, Inc. | Catheter for target specific drug delivery |
| US20030170891A1 (en) * | 2001-06-06 | 2003-09-11 | Mcswiggen James A. | RNA interference mediated inhibition of epidermal growth factor receptor gene expression using short interfering nucleic acid (siNA) |
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| WO2004064737A2 (en) | 2003-01-17 | 2004-08-05 | Alnylam Pharmaceuticals | Therapeutics compositions |
| ATE479752T1 (de) | 2003-03-07 | 2010-09-15 | Alnylam Pharmaceuticals Inc | Therapeutische zusammensetzungen |
| US20040191291A1 (en) | 2003-03-28 | 2004-09-30 | Masaya Tohyama | Composition and method for nerve regeneration |
| JP2007528202A (ja) * | 2003-03-28 | 2007-10-11 | 株式会社インテレクチャル・プロパティ・コンサルティング | 神経再生のための組成物および方法 |
| US20040198640A1 (en) * | 2003-04-02 | 2004-10-07 | Dharmacon, Inc. | Stabilized polynucleotides for use in RNA interference |
| DK1620544T3 (en) | 2003-04-17 | 2019-01-14 | Alnylam Pharmaceuticals Inc | MODIFIED iRNA AGENTS |
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| FR2857768B1 (fr) | 2003-07-18 | 2006-01-06 | Atmel Grenoble Sa | Procede d'acquisition d'image d'empreinte digitale |
| CN101084309A (zh) | 2004-10-22 | 2007-12-05 | 诺伊热尼有限公司 | 神经元再生 |
| ATE541928T1 (de) * | 2005-03-31 | 2012-02-15 | Calando Pharmaceuticals Inc | Inhibitoren der untereinheit 2 der ribonukleotidreduktase und ihre verwendungen |
| WO2007014077A2 (en) * | 2005-07-21 | 2007-02-01 | Alnylam Pharmaceuticals, Inc. | Rnai modulation of the rho-a gene and uses thereof |
| KR20150038522A (ko) * | 2006-03-31 | 2015-04-08 | 알닐람 파마슈티칼스 인코포레이티드 | Ｅｇ5 유전자의 발현을 억제하는 이본쇄 리보핵산 |
| US8598333B2 (en) * | 2006-05-26 | 2013-12-03 | Alnylam Pharmaceuticals, Inc. | SiRNA silencing of genes expressed in cancer |
-
2006
- 2006-07-21 WO PCT/US2006/028488 patent/WO2007014077A2/en not_active Ceased
- 2006-07-21 EP EP06788187A patent/EP1909850A4/en not_active Withdrawn
- 2006-07-21 US US11/491,367 patent/US7772200B2/en active Active
- 2006-07-21 AU AU2006272808A patent/AU2006272808C1/en active Active
- 2006-07-21 EP EP10007181A patent/EP2230305A1/en not_active Withdrawn
- 2006-07-21 CA CA002607668A patent/CA2607668A1/en not_active Abandoned
- 2006-07-21 WO PCT/US2006/028486 patent/WO2007014075A2/en not_active Ceased
- 2006-07-21 US US11/491,440 patent/US20070044161A1/en not_active Abandoned
- 2006-07-21 JP JP2008523010A patent/JP2009502138A/ja active Pending
-
2010
- 2010-07-27 AU AU2010206007A patent/AU2010206007B2/en active Active
- 2010-07-30 US US12/847,958 patent/US20110071209A1/en not_active Abandoned
-
2011
- 2011-08-03 JP JP2011170509A patent/JP2011250796A/ja active Pending
- 2011-12-22 JP JP2011282081A patent/JP2012061007A/ja not_active Withdrawn
Also Published As
| Publication number | Publication date |
|---|---|
| AU2006272808B2 (en) | 2010-04-29 |
| US7772200B2 (en) | 2010-08-10 |
| AU2006272808C1 (en) | 2010-10-21 |
| WO2007014075A2 (en) | 2007-02-01 |
| US20070042984A1 (en) | 2007-02-22 |
| WO2007014077A2 (en) | 2007-02-01 |
| EP1909850A2 (en) | 2008-04-16 |
| JP2011250796A (ja) | 2011-12-15 |
| AU2010206007A1 (en) | 2010-08-19 |
| JP2012061007A (ja) | 2012-03-29 |
| JP2009502138A (ja) | 2009-01-29 |
| AU2010206007B2 (en) | 2011-12-08 |
| EP2230305A1 (en) | 2010-09-22 |
| US20070044161A1 (en) | 2007-02-22 |
| EP1909850A4 (en) | 2010-05-12 |
| WO2007014077A3 (en) | 2007-12-06 |
| AU2006272808A1 (en) | 2007-02-01 |
| WO2007014075A3 (en) | 2009-04-23 |
| US20110071209A1 (en) | 2011-03-24 |
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| FZDE | Discontinued |
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