AU2006235489A1 - Composition and methods of RNAi therapeutics for treatment of cancer and other neovascularization diseases - Google Patents
Composition and methods of RNAi therapeutics for treatment of cancer and other neovascularization diseases Download PDFInfo
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- AU2006235489A1 AU2006235489A1 AU2006235489A AU2006235489A AU2006235489A1 AU 2006235489 A1 AU2006235489 A1 AU 2006235489A1 AU 2006235489 A AU2006235489 A AU 2006235489A AU 2006235489 A AU2006235489 A AU 2006235489A AU 2006235489 A1 AU2006235489 A1 AU 2006235489A1
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| US7148342B2 (en) | 2002-07-24 | 2006-12-12 | The Trustees Of The University Of Pennyslvania | Compositions and methods for sirna inhibition of angiogenesis |
| US7612196B2 (en) | 2002-11-14 | 2009-11-03 | Dharmacon, Inc. | siRNA targeting cyclin-dependent kinase inhibitor 1B (p27, Kip1) (CDKN1B) |
| US9771586B2 (en) | 2002-11-14 | 2017-09-26 | Thermo Fisher Scientific Inc. | RNAi targeting ZNF205 |
| DK2284266T3 (da) | 2002-11-14 | 2014-01-13 | Thermo Fisher Scient Biosciences Inc | sIRNA-MOLEKYLE MOD TP53 |
| US8198427B1 (en) | 2002-11-14 | 2012-06-12 | Dharmacon, Inc. | SiRNA targeting catenin, beta-1 (CTNNB1) |
| WO2006006948A2 (en) | 2002-11-14 | 2006-01-19 | Dharmacon, Inc. | METHODS AND COMPOSITIONS FOR SELECTING siRNA OF IMPROVED FUNCTIONALITY |
| US7977471B2 (en) | 2002-11-14 | 2011-07-12 | Dharmacon, Inc. | siRNA targeting TNFα |
| US9839649B2 (en) | 2002-11-14 | 2017-12-12 | Thermo Fisher Scientific Inc. | Methods and compositions for selecting siRNA of improved functionality |
| US7635770B2 (en) | 2002-11-14 | 2009-12-22 | Dharmacon, Inc. | siRNA targeting protein kinase N-3 (PKN-3) |
| US9228186B2 (en) | 2002-11-14 | 2016-01-05 | Thermo Fisher Scientific Inc. | Methods and compositions for selecting siRNA of improved functionality |
| US7619081B2 (en) | 2002-11-14 | 2009-11-17 | Dharmacon, Inc. | siRNA targeting coatomer protein complex, subunit beta 2 (COPB2) |
| US7951935B2 (en) | 2002-11-14 | 2011-05-31 | Dharmacon, Inc. | siRNA targeting v-myc myelocytomatosis viral oncogene homolog (MYC) |
| US9719092B2 (en) | 2002-11-14 | 2017-08-01 | Thermo Fisher Scientific Inc. | RNAi targeting CNTD2 |
| US7592442B2 (en) | 2002-11-14 | 2009-09-22 | Dharmacon, Inc. | siRNA targeting ribonucleotide reductase M2 polypeptide (RRM2 or RNR-R2) |
| US7691998B2 (en) | 2002-11-14 | 2010-04-06 | Dharmacon, Inc. | siRNA targeting nucleoporin 62kDa (Nup62) |
| US9719094B2 (en) | 2002-11-14 | 2017-08-01 | Thermo Fisher Scientific Inc. | RNAi targeting SEC61G |
| US10011836B2 (en) | 2002-11-14 | 2018-07-03 | Thermo Fisher Scientific Inc. | Methods and compositions for selecting siRNA of improved functionality |
| US9879266B2 (en) | 2002-11-14 | 2018-01-30 | Thermo Fisher Scientific Inc. | Methods and compositions for selecting siRNA of improved functionality |
| MXPA06007269A (es) | 2003-12-23 | 2007-07-09 | Univ Pennsylvania | Composiciones y metodos para terapia combinada de enfermedad. |
| US8491914B2 (en) * | 2004-02-13 | 2013-07-23 | Ibc Pharmaceuticals, Inc. | Dock-and-lock (DNL) complexes for delivery of interference RNA |
| US7605250B2 (en) | 2004-05-12 | 2009-10-20 | Dharmacon, Inc. | siRNA targeting cAMP-specific phosphodiesterase 4D |
| US7893244B2 (en) * | 2005-04-12 | 2011-02-22 | Intradigm Corporation | Composition and methods of RNAi therapeutics for treatment of cancer and other neovascularization diseases |
| SG161267A1 (en) * | 2005-04-12 | 2010-05-27 | Intradigm Corp | Composition and methods of rnai therapeutics for treatment of cancer and other neovascularization diseases |
| US20070082845A1 (en) * | 2005-07-15 | 2007-04-12 | The Penn State Research Foundation | Ferritin as a therapeutic target in abnormal cells |
| CA2625473A1 (en) * | 2005-10-14 | 2007-04-26 | Nastech Pharmaceutical Company Inc. | Compounds and methods for peptide ribonucleic acid condensate particles for rna therapeutics |
| WO2007080902A1 (ja) * | 2006-01-11 | 2007-07-19 | Kyowa Hakko Kogyo Co., Ltd. | 眼球において標的遺伝子の発現を抑制する組成物および眼球における疾患の治療剤 |
| HUE037173T2 (hu) | 2006-08-08 | 2018-08-28 | Univ Bonn Rheinische Friedrich Wilhelms | 5'-Foszfát-oligonukleotidok szerkezete és alkalmazása |
| WO2008045576A2 (en) * | 2006-10-12 | 2008-04-17 | Yijia Liu | Compositions and methods of rnai therapeutics for treatment of cancer and other neovascularization diseases |
| US20080274121A1 (en) * | 2007-04-30 | 2008-11-06 | Yao James C | Inhibition of Angiogenesis by Mithramycin |
| CN101363027B (zh) * | 2007-08-06 | 2011-07-27 | 武汉大学 | 携带短发夹rna的重组质粒的制备方法及用途 |
| WO2009031671A1 (ja) * | 2007-09-07 | 2009-03-12 | The University Of Tokushima | p53の発現促進方法およびそれに用いるp53発現促進剤 |
| EP2209895A2 (en) * | 2007-10-12 | 2010-07-28 | Intradigm Corporation | Therapeutic sirna molecules for reducing vegfr1 expression in vitro and in vivo |
| CN101917846B (zh) * | 2007-11-06 | 2014-06-25 | 圣诺制药公司 | 用于皮肤伤口无疤痕愈合的多靶标RNAi治疗 |
| JP2011504943A (ja) * | 2007-11-07 | 2011-02-17 | ユニバーシティ・オブ・ユタ・リサーチ・ファウンデイション | ヌクレオチド送達を亢進するための、還元可能なポリ(アミドエチレンイミン)に対する切断可能な修飾 |
| KR101617790B1 (ko) * | 2008-02-26 | 2016-05-03 | 아파르나 바이오사이언시스 | 치료, 진단과 실험적 혼합물들의 운반을 위한 공학적으로 가변된 나노입자 및 치료용 관련 조성물 |
| ES2338400B1 (es) * | 2008-05-06 | 2011-09-14 | David Benet Ferrus | Conjunto de moleculas antiangiogenicas y su uso. |
| EP2297323A1 (en) | 2008-05-21 | 2011-03-23 | Hartmann, Gunther | 5' triphosphate oligonucleotide with blunt end and uses thereof |
| WO2009151539A1 (en) * | 2008-05-24 | 2009-12-17 | Sirnaomics, Inc. | COMPOSITIONS AND METHODS USING siRNA MOLECULES FOR TREATMENT OF GLIOMAS |
| MX2011005851A (es) | 2008-12-04 | 2011-07-29 | Opko Opthalmics Llc | Composiciones y metodos para la inhibicion selectiva de isoformas vegf proangiogenicas. |
| US9012622B2 (en) | 2008-12-31 | 2015-04-21 | Patrick Y. Lu | Compositions and methods using siRNA molecules and siRNA cocktails for the treatment of breast cancer |
| DE102009006606A1 (de) * | 2009-01-29 | 2010-08-05 | Philipps-Universität Marburg | Nicht-virales Transfektionsmittel |
| CA2762524A1 (en) * | 2009-05-18 | 2011-01-13 | Ensysce Biosciences, Inc. | Carbon nanotubes complexed with multiple bioactive agents and methods related thereto |
| WO2011011061A2 (en) * | 2009-07-21 | 2011-01-27 | The Board Of Trustees Of The Leland Stanford Junior University | Method of regulating angiogenesis and lymphangiogenesis, and a pharmaceutical composition for effecting anti-angiogenic and anti-lymphangiogenic cancer therapy |
| WO2011039646A2 (en) | 2009-09-30 | 2011-04-07 | Inserm (Institut National De La Sante Et De La Recherche Medicale) | Papilloma virus -like particles for targeted gene delivery |
| EP2549986B1 (en) * | 2010-03-24 | 2019-10-30 | Northeastern University | Multi-compartmental macrophage delivery |
| WO2011120053A1 (en) | 2010-03-26 | 2011-09-29 | Mersana Therapeutics, Inc. | Modified polymers for delivery of polynucleotides, method of manufacture, and methods of use thereof |
| CN102985546A (zh) | 2010-05-04 | 2013-03-20 | 圣诺制药公司 | TGF-beta和Cox-2抑制剂的联合及其治疗应用的方法 |
| WO2012016139A2 (en) | 2010-07-29 | 2012-02-02 | Sirnaomics, Inc. | Sirna compositions and methods for treatment of hpv and other infections |
| EP2508530A1 (en) | 2011-03-28 | 2012-10-10 | Rheinische Friedrich-Wilhelms-Universität Bonn | Purification of triphosphorylated oligonucleotides using capture tags |
| CN102727513B (zh) * | 2011-04-15 | 2014-07-09 | 百奥迈科生物技术有限公司 | 靶向于组织因子基因的小核酸及其用途 |
| US8592572B2 (en) * | 2011-05-23 | 2013-11-26 | Delta-Fly Pharma, Inc. | Liposome containing shRNA molecule targeting a thymidylate synthase and use thereof |
| US20120301537A1 (en) * | 2011-05-23 | 2012-11-29 | Delta-Fly Pharma, Inc. | LIPOSOME CONTAINING shRNA MOLECULE TARGETING A THYMIDYLATE SYNTHASE AND USE THEREOF |
| AU2013216361B2 (en) | 2012-02-02 | 2017-09-07 | The University Of British Columbia | Combination therapy for cancer using HSP27 inhibitor and EGFR tyrosine kinase inhibitors or anti-folates |
| EP2712870A1 (en) | 2012-09-27 | 2014-04-02 | Rheinische Friedrich-Wilhelms-Universität Bonn | Novel RIG-I ligands and methods for producing them |
| US9801953B2 (en) | 2012-10-15 | 2017-10-31 | Emory University | Nanoparticles carrying nucleic acid cassettes for expressing RNA |
| US9228189B2 (en) | 2012-10-26 | 2016-01-05 | Geron Corporation | C-myc antisense oligonucleotides and methods for using the same to treat cell-proliferative disorders |
| CN105451743B (zh) * | 2013-08-07 | 2019-11-19 | 箭头研究公司 | 用于在活体中递送RNAi触发子至肿瘤细胞的聚偶联物 |
| CN104635967B (zh) * | 2013-11-12 | 2018-04-10 | 宸鸿光电科技股份有限公司 | 有机发光二极管触控显示设备 |
| RS58337B1 (sr) * | 2014-03-24 | 2019-03-29 | Translate Bio Inc | Irnk terapija za lečenje očnih oboljenja |
| CA2978449A1 (en) | 2015-03-02 | 2016-09-09 | 180 Therapeutics Lp | Method of treating a localized fibrotic disorder using an il-33 antagonist |
| AU2017368050A1 (en) | 2016-11-29 | 2019-06-20 | Puretech Lyt, Inc. | Exosomes for delivery of therapeutic agents |
| CN111298129B (zh) * | 2019-08-28 | 2023-05-09 | 中国人民解放军陆军军医大学第二附属医院 | 二甲双胍介导核酸纳米材料自组装方法及采用该方法制备的纳米制剂和应用 |
Family Cites Families (88)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5240848A (en) * | 1988-11-21 | 1993-08-31 | Monsanto Company | Dna sequences encoding human vascular permeability factor having 189 amino acids |
| US5332671A (en) * | 1989-05-12 | 1994-07-26 | Genetech, Inc. | Production of vascular endothelial cell growth factor and DNA encoding same |
| US5726152A (en) * | 1990-09-21 | 1998-03-10 | Merck & Co., Inc. | Vascular endothelial cell growth factor II |
| EP0506477B1 (en) * | 1991-03-28 | 1999-06-23 | Merck & Co. Inc. | Vascular endothelial cell growth factor C subunit |
| US6710174B2 (en) | 2001-09-13 | 2004-03-23 | Isis Pharmaceuticals, Inc. | Antisense inhibition of vascular endothelial growth factor receptor-1 expression |
| US6743909B2 (en) * | 2002-06-17 | 2004-06-01 | Isis Pharmaceuticals, Inc. | Antisense modulation of PTPN12 expression |
| US6037329A (en) * | 1994-03-15 | 2000-03-14 | Selective Genetics, Inc. | Compositions containing nucleic acids and ligands for therapeutic treatment |
| EP0769552A4 (en) * | 1994-06-27 | 1997-06-18 | Toagosei Co Ltd | ANTISENSE NUCLEIC ACID COMPOUND |
| AU3374795A (en) | 1994-08-29 | 1996-03-22 | Prizm Pharmaceuticals, Inc. | Conjugates of vascular endothelial growth factor with targeted agents |
| WO1996020403A1 (en) | 1994-12-23 | 1996-07-04 | Ludwig Institute For Cancer Research | Assay, receptor proteins and ligands |
| US5607918A (en) * | 1995-03-01 | 1997-03-04 | Ludwig Institute For Cancer Research | Vascular endothelial growth factor-B and DNA coding therefor |
| US5928939A (en) * | 1995-03-01 | 1999-07-27 | Ludwig Institute For Cancer Research | Vascular endothelial growth factor-b and dna coding therefor |
| WO1997006814A1 (en) * | 1995-08-15 | 1997-02-27 | Connective Therapeutics, Inc. | Method of promoting angiogenesis |
| US7005505B1 (en) * | 1995-08-25 | 2006-02-28 | Genentech, Inc. | Variants of vascular endothelial cell growth factor |
| US6346398B1 (en) | 1995-10-26 | 2002-02-12 | Ribozyme Pharmaceuticals, Inc. | Method and reagent for the treatment of diseases or conditions related to levels of vascular endothelial growth factor receptor |
| US20040142895A1 (en) * | 1995-10-26 | 2004-07-22 | Sirna Therapeutics, Inc. | Nucleic acid-based modulation of gene expression in the vascular endothelial growth factor pathway |
| EP1426444A3 (en) | 1996-09-06 | 2004-06-16 | Technion Research & Development Co., Ltd. | Use of the angiogenic factor VEGF145 in treating cardiovascular diseases |
| US6013780A (en) * | 1996-09-06 | 2000-01-11 | Technion Research & Development Co. Ltd. | VEGF145 expression vectors |
| US6750044B1 (en) * | 1996-10-17 | 2004-06-15 | Genentech, Inc. | Variants of vascular endothelial cell growth factor having antagonistic properties, nucleic acids encoding the same and host cells comprising those nucleic acids |
| US6485942B1 (en) * | 1997-02-14 | 2002-11-26 | Genentech, Inc. | Variants of vascular endothelial cell growth factor having altered pharmacological properties, and recombinant methods of production |
| US6395707B1 (en) * | 1997-02-14 | 2002-05-28 | Genentech, Inc. | Methods of treatment utilizing variants of vascular endothelial cell growth factor |
| US6479729B1 (en) * | 1998-02-06 | 2002-11-12 | The Johns Hopkins University | Mouse model for ocular neovascularization |
| AU767662B2 (en) * | 1998-02-06 | 2003-11-20 | Collateral Therapeutics, Inc. | Variants of the angiogenic factor vascular endothelial cell growth factor: VEGF |
| US6783961B1 (en) * | 1999-02-26 | 2004-08-31 | Genset S.A. | Expressed sequence tags and encoded human proteins |
| WO1999063975A2 (en) | 1998-06-10 | 1999-12-16 | Biognostik Gesellschaft für Biomolekulare Diagnostik mbH | A method for stimulating the immune system |
| AU4438399A (en) | 1998-06-11 | 1999-12-30 | University Of Medicine And Dentistry Of New Jersey | Wound treatment through inhibition of adenosine diphosphate ribosyl transferase |
| EP0979869A1 (en) * | 1998-08-07 | 2000-02-16 | Hoechst Marion Roussel Deutschland GmbH | Short oligonucleotides for the inhibition of VEGF expression |
| US7030083B2 (en) * | 1998-09-09 | 2006-04-18 | University Of Washington | Treatment of eclampsia and preeclampsia |
| JP2002524421A (ja) * | 1998-09-09 | 2002-08-06 | サイオス インコーポレイテッド | 微小血管障害の処置 |
| US6677300B1 (en) * | 1998-09-09 | 2004-01-13 | Scios, Inc. | Treatment of microvascular angiopathies |
| EP1417971A3 (en) | 1998-09-09 | 2004-06-30 | Scios Inc. | Use of an angiogenic factor for the treatment of microvascular angiopathies |
| US6916915B1 (en) * | 1998-11-20 | 2005-07-12 | Duke University | Stressor regulated genes |
| CA2296792A1 (en) | 1999-02-26 | 2000-08-26 | Genset S.A. | Expressed sequence tags and encoded human proteins |
| IL128852A0 (en) * | 1999-03-05 | 2000-01-31 | Compugen Ltd | Novel nucleic acid and amino acid sequences |
| US6783954B2 (en) * | 1999-03-05 | 2004-08-31 | Compugen Ltd. | VEGF nucleic acid and amino acid sequences |
| DE19910419A1 (de) | 1999-03-10 | 2000-09-21 | Aventis Pharma Gmbh | Zielzellspezifische, multivalente Proteine (MVP) |
| US6943153B1 (en) * | 1999-03-15 | 2005-09-13 | The Regents Of The University Of California | Use of recombinant gene delivery vectors for treating or preventing diseases of the eye |
| AU5023300A (en) * | 1999-05-20 | 2000-12-12 | Scios Inc. | Vascular endothelial growth factor variants |
| US6187822B1 (en) * | 1999-06-11 | 2001-02-13 | University Of Medicine & Dentistry Of Nj | Wound treatment through inhibition of adenosine diphosphate ribosyl transferase |
| AU7546600A (en) | 1999-10-08 | 2001-04-23 | Biofocus Discovery Limited | Methods and compositions for targeting a cell |
| US6770633B1 (en) * | 1999-10-26 | 2004-08-03 | Immusol, Inc. | Ribozyme therapy for the treatment of proliferative skin and eye diseases |
| US7078382B1 (en) * | 1999-11-02 | 2006-07-18 | Genentech, Inc. | Modulation of eNOS activity and therapeutic uses thereof |
| AU2001229254B2 (en) * | 2000-01-19 | 2006-07-27 | Gill, Parkash S. | Pharmaceutical compositions and methods of treatment based on VEGF antisense oligonucleotides |
| EP1253929B1 (en) | 2000-02-09 | 2007-05-23 | BAS Medical, Inc. | Use of relaxin to treat diseases related to vasoconstriction |
| WO2001062942A2 (en) * | 2000-02-25 | 2001-08-30 | Ludwig Institute For Cancer Research | MATERIALS AND METHODS INVOLVING HYBRID VASCULAR ENDOTHELIAL GROWTH FACTOR DNAs AND PROTEINS AND SCREENING METHODS FOR MODULATORS |
| US6974667B2 (en) * | 2000-06-14 | 2005-12-13 | Gene Logic, Inc. | Gene expression profiles in liver cancer |
| US6727066B2 (en) * | 2000-07-28 | 2004-04-27 | Incyte Corporation | Genes expressed in treated human C3A liver cell cultures |
| US6673549B1 (en) * | 2000-10-12 | 2004-01-06 | Incyte Corporation | Genes expressed in C3A liver cell cultures treated with steroids |
| US20030186920A1 (en) | 2000-10-13 | 2003-10-02 | Sirois Martin G. | Antisense oligonucleotide directed toward mammalian vegf receptor genes and uses thereof |
| US20070021360A1 (en) | 2001-04-24 | 2007-01-25 | Nyce Jonathan W | Compositions, formulations and kit with anti-sense oligonucleotide and anti-inflammatory steroid and/or obiquinone for treatment of respiratory and lung disesase |
| WO2002085309A2 (en) | 2001-04-24 | 2002-10-31 | Epigenesis Pharmaceuticals, Inc. | Composition, formulations & kits for treatment of respiratory & lung disease with anti-sense oligonucleotides & a bronchodilating agent |
| US20050222066A1 (en) * | 2001-05-18 | 2005-10-06 | Sirna Therapeutics, Inc. | RNA interference mediated inhibition of vascular endothelial growth factor and vascular endothelial growth factor receptor gene expression using short interfering nucleic acid (siNA) |
| CA2526831C (en) * | 2001-05-18 | 2012-07-31 | Sirna Therapeutics, Inc. | Rna interference mediated inhibition of gene expression using chemically modified short interfering nucleic acid (sina) |
| US20050148530A1 (en) * | 2002-02-20 | 2005-07-07 | Sirna Therapeutics, Inc. | RNA interference mediated inhibition of vascular endothelial growth factor and vascular endothelial growth factor receptor gene expression using short interfering nucleic acid (siNA) |
| WO2004111237A1 (en) | 2003-04-16 | 2004-12-23 | Sirna Therapeutics, Inc. | RNA INTERFERENCE MEDIATED INHIBITION OF PLATELET-DERIVED ENDOTHELIAL CELL GROWTH FACTOR (ECGF1) GENE EXPRESSION USING SHORT INTERFERING NUCLEIC ACID (siNA) |
| WO2003070910A2 (en) | 2002-02-20 | 2003-08-28 | Ribozyme Pharmaceuticals, Incorporated | INHIBITION OF VASCULAR ENDOTHELIAL GROWTH FACTOR (VEGF) AND VEGF RECEPTOR GENE EXPRESSION USING SHORT INTERFERING NUCLEIC ACID (siNA) |
| US7517864B2 (en) | 2001-05-18 | 2009-04-14 | Sirna Therapeutics, Inc. | RNA interference mediated inhibition of vascular endothelial growth factor and vascular endothelial growth factor receptor gene expression using short interfering nucleic acid (siNA) |
| EP1262199A1 (en) | 2001-05-23 | 2002-12-04 | Fornix Biosciences N.V. | Vectors for enhanced expression of VEGF for disease treatment |
| CA2448320A1 (en) | 2001-05-29 | 2002-12-05 | Sirna Therapeutics, Inc. | Ribozyme based treatment of female reproductive diseases |
| CA2454048C (en) * | 2001-07-17 | 2011-05-03 | Research Development Foundation | Therapeutic agents comprising pro-apoptotic proteins |
| JP2003088388A (ja) * | 2001-09-14 | 2003-03-25 | Herikkusu Kenkyusho:Kk | 新規な全長cDNA |
| EP1293569A3 (en) | 2001-09-14 | 2004-03-31 | Research Association for Biotechnology | Full-length cDNAs |
| WO2003040399A2 (en) * | 2001-11-02 | 2003-05-15 | Intradigm Corporation | Therapeutic methods for nucleic acid delivery vehicles |
| FR2832154B1 (fr) | 2001-11-09 | 2007-03-16 | Centre Nat Rech Scient | Oligonucleotides inhibiteurs et leur utilisation pour reprimer specifiquement un gene |
| US20050075304A1 (en) * | 2001-11-30 | 2005-04-07 | Mcswiggen James | RNA interference mediated inhibition of vascular endothelial growth factor and vascular endothelial growth factor receptor gene expression using short interfering nucleic acid (siNA) |
| US6927779B2 (en) * | 2002-05-13 | 2005-08-09 | Large Scale Biology Corporation | Web-based well plate information retrieval and display system |
| US7148342B2 (en) * | 2002-07-24 | 2006-12-12 | The Trustees Of The University Of Pennyslvania | Compositions and methods for sirna inhibition of angiogenesis |
| AU2003279004B2 (en) * | 2002-09-28 | 2009-10-08 | Massachusetts Institute Of Technology | Influenza therapeutic |
| DK2284266T3 (da) | 2002-11-14 | 2014-01-13 | Thermo Fisher Scient Biosciences Inc | sIRNA-MOLEKYLE MOD TP53 |
| FR2835838B1 (fr) | 2003-02-06 | 2007-11-16 | Centre Nat Rech Scient | Oligonucleotides inhibiteurs et leur utilisation pour reprimer specifiquement un gene codant pour un facteur de transcription |
| FR2835837B1 (fr) | 2003-02-06 | 2007-03-16 | Centre Nat Rech Scient | Oligonucleotides inhibiteurs et leurs utilisation pour reprimer specifiquement un gene codant pour un facteur de croissance |
| EP1608735A4 (en) * | 2003-04-03 | 2008-11-05 | Alnylam Pharmaceuticals | RNAI CONJUGATES |
| US20050096370A1 (en) | 2003-04-07 | 2005-05-05 | Bizbiotech Co., Ltd. | Method for inhibiting tumor angiogenesis and tumor growth |
| DE10316701A1 (de) | 2003-04-09 | 2004-11-04 | Hinzmann, Bernd, Dr. | Humane Nukleinsäuresequenzen aus Bronchialkarzinomen |
| US20050019927A1 (en) * | 2003-07-13 | 2005-01-27 | Markus Hildinger | DECREASING GENE EXPRESSION IN A MAMMALIAN SUBJECT IN VIVO VIA AAV-MEDIATED RNAi EXPRESSION CASSETTE TRANSFER |
| EP1548445A3 (en) | 2003-12-22 | 2005-11-23 | F. Hoffmann-La Roche Ag | Novel targets for obesity from fat tissue |
| CN101044152A (zh) * | 2004-02-05 | 2007-09-26 | 因特拉迪格姆公司 | 组合RNAi治疗的方法和组合物 |
| US20090247604A1 (en) * | 2004-02-05 | 2009-10-01 | Intradigm Corporation | RNAi Therapeutics for Treatment of Eye Neovascularization Diseases |
| AU2005222902B2 (en) * | 2004-03-12 | 2010-06-10 | Alnylam Pharmaceuticals, Inc. | iRNA agents targeting VEGF |
| AU2005248147A1 (en) | 2004-05-11 | 2005-12-08 | Alphagen Co., Ltd. | Polynucleotides for causing RNA interference and method for inhibiting gene expression using the same |
| EP1607485A1 (en) | 2004-06-14 | 2005-12-21 | Institut National De La Sante Et De La Recherche Medicale (Inserm) | Method for quantifying VEGF121 isoform in a biological sample |
| JP2008520209A (ja) * | 2004-11-17 | 2008-06-19 | ユニヴァーシティ・オブ・メリーランド,バルチモア | siRNAの有効なキャリアとしての高度に枝分かれしたHKペプチド |
| US7893244B2 (en) | 2005-04-12 | 2011-02-22 | Intradigm Corporation | Composition and methods of RNAi therapeutics for treatment of cancer and other neovascularization diseases |
| SG161267A1 (en) | 2005-04-12 | 2010-05-27 | Intradigm Corp | Composition and methods of rnai therapeutics for treatment of cancer and other neovascularization diseases |
| EP1714970A1 (en) | 2005-04-22 | 2006-10-25 | Universität des Saarlandes | Use of inhibitors of RNAse A-family enzymes for stabilizing oligonucleotides having RNA interfering activity |
| CN100374573C (zh) | 2006-04-14 | 2008-03-12 | 中国医学科学院医药生物技术研究所 | 一种可稳定表达VEGF shRNA的载体pCD-VEGF |
| WO2008045576A2 (en) | 2006-10-12 | 2008-04-17 | Yijia Liu | Compositions and methods of rnai therapeutics for treatment of cancer and other neovascularization diseases |
| EP2209895A2 (en) | 2007-10-12 | 2010-07-28 | Intradigm Corporation | Therapeutic sirna molecules for reducing vegfr1 expression in vitro and in vivo |
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| US7893243B2 (en) | 2011-02-22 |
| BRPI0610499A2 (pt) | 2010-06-22 |
| US20080153771A1 (en) | 2008-06-26 |
| US7534878B2 (en) | 2009-05-19 |
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| US20090118208A1 (en) | 2009-05-07 |
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| KR20080041145A (ko) | 2008-05-09 |
| US20090227657A1 (en) | 2009-09-10 |
| WO2006110813A2 (en) | 2006-10-19 |
| WO2006110813A3 (en) | 2007-11-15 |
| US20080220027A1 (en) | 2008-09-11 |
| EP1877065A4 (en) | 2010-12-22 |
| MX2007012766A (es) | 2008-10-01 |
| IL186578A0 (en) | 2008-01-20 |
| CA2604441A1 (en) | 2006-10-19 |
| SG161267A1 (en) | 2010-05-27 |
| US20080241198A1 (en) | 2008-10-02 |
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