CA2723672C - Gene expression and pain - Google Patents
Gene expression and pain Download PDFInfo
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- CA2723672C CA2723672C CA2723672A CA2723672A CA2723672C CA 2723672 C CA2723672 C CA 2723672C CA 2723672 A CA2723672 A CA 2723672A CA 2723672 A CA2723672 A CA 2723672A CA 2723672 C CA2723672 C CA 2723672C
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Classifications
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- C12N15/09—Recombinant DNA-technology
- C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
- C12N15/113—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H21/00—Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids
- C07H21/04—Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids with deoxyribosyl as saccharide radical
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/10—Type of nucleic acid
- C12N2310/13—Decoys
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
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- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
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| US8609617B2 (en) | 2009-09-04 | 2013-12-17 | University Of Miami | KLF family members regulate intrinsic axon regeneration ability |
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| AU2013259402B2 (en) * | 2012-05-10 | 2017-12-21 | Adynxx, Inc. | Formulations for the delivery of active ingredients |
| BR112015000723A2 (pt) | 2012-07-13 | 2017-06-27 | Shin Nippon Biomedical Laboratories Ltd | adjuvante de ácido nucléico quiral |
| PT2872485T (pt) | 2012-07-13 | 2021-03-05 | Wave Life Sciences Ltd | Grupo auxiliar assimétrico |
| KR102712879B1 (ko) | 2012-07-13 | 2024-10-04 | 웨이브 라이프 사이언시스 리미티드 | 키랄 제어 |
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| JPWO2015108046A1 (ja) | 2014-01-15 | 2017-03-23 | 株式会社新日本科学 | 抗アレルギー作用を有するキラル核酸アジュバンド及び抗アレルギー剤 |
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Family Cites Families (72)
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| ATE357922T1 (de) | 1995-05-12 | 2007-04-15 | Anges Mg Inc | Heilung und vorbeugung von durch nf-kappab verursachten erkrankungen |
| GB9515356D0 (en) | 1995-07-26 | 1995-09-20 | Medical Res Council | Improvements in or relating to delivery of nucleic acid |
| US6265389B1 (en) | 1995-08-31 | 2001-07-24 | Alkermes Controlled Therapeutics, Inc. | Microencapsulation and sustained release of oligonucleotides |
| DE69738454D1 (de) | 1996-05-20 | 2008-02-21 | Us Gov Health & Human Serv | Oligonukleotide welche spezifisch retrovirale nukleokapsid-proteine binden |
| US6022863A (en) | 1996-05-21 | 2000-02-08 | Yale University | Regulation of gene expression |
| US6890909B1 (en) | 1997-07-04 | 2005-05-10 | Fujisawa Pharmaceutical Co., Ltd. | Brain-protective agent |
| JP3667047B2 (ja) | 1997-09-12 | 2005-07-06 | キヤノン株式会社 | 人工核酸およびその製造方法、デオキシリボフラノース化合物、リボフラノース化合物およびこれらの製造方法 |
| AU9692198A (en) | 1997-10-10 | 1999-05-03 | Kevin J. Donahue | Gene delivery compositions and methods |
| US6060310A (en) | 1997-11-24 | 2000-05-09 | The United States Of America As Represented By The Department Of Health And Human Services | Transcription factor decoy and tumor growth inhibitor |
| AU1656299A (en) | 1997-12-16 | 1999-07-05 | University Of Saskatchewan | Conductive metal-containing nucleic acids |
| JP2002516676A (ja) | 1998-06-02 | 2002-06-11 | グラクソ グループ リミテッド | 遺伝子治療法 |
| US6818626B1 (en) | 1998-07-17 | 2004-11-16 | Mirus Corporation | Chelating systems for use in the delivery of compounds to cells |
| US6423493B1 (en) | 1998-10-26 | 2002-07-23 | Board Of Regents The University Of Texas System | Combinatorial selection of oligonucleotide aptamers |
| US6008048A (en) | 1998-12-04 | 1999-12-28 | Isis Pharmaceuticals Inc. | Antisense inhibition of EGR-1 expression |
| US7160869B2 (en) | 1998-12-16 | 2007-01-09 | University Of Saskatchewan | Biologically active metal-containing nucleic acids |
| ATE354667T1 (de) | 1998-12-23 | 2007-03-15 | Genentech Inc | Transfectaconen, die kalciumphosphat und eine nucleinsäure enthalten |
| US6395029B1 (en) | 1999-01-19 | 2002-05-28 | The Children's Hospital Of Philadelphia | Sustained delivery of polyionic bioactive agents |
| US6333408B1 (en) | 1999-03-08 | 2001-12-25 | Kureha Chemical Industry Co., Ltd. | Oligonucleotides inhibitors of PAI-1 MRNA |
| FR2790955B1 (fr) | 1999-03-19 | 2003-01-17 | Assist Publ Hopitaux De Paris | Utilisation d'oligonucleotides stabilises comme principe actif antitumoral |
| CA2300328A1 (en) | 1999-09-14 | 2001-03-14 | Cardiogene Gentherap. Systeme Ag | Modulating transcription of genes in vascular cells |
| US6927027B2 (en) | 1999-12-21 | 2005-08-09 | Ingeneus Corporation | Nucleic acid multiplex formation |
| US6969704B1 (en) | 2000-08-25 | 2005-11-29 | The Trustees Of Columbia University In The City Of New York | Methods for suppressing early growth response—1protein (Egr-1) to reduce vascular injury in a subject |
| DE10049549A1 (de) | 2000-10-06 | 2002-05-02 | Markus Hecker | Modulation der Transkription pro-inflammatorischer Genprodukte |
| CA2462081A1 (en) | 2000-10-11 | 2002-04-18 | Laura Kragie | Composition and method of alleviating adverse side effects and/or enhancing efficacy of agents that inhibit aromatase |
| EP1344536A4 (en) | 2000-11-24 | 2005-01-19 | Chugai Pharmaceutical Co Ltd | METHOD FOR REGULATING THE ACTIVITY OF EXPRESSION OF A GENETIC PRODUCT TRANSFERRED INTO A LIVING ORGANISM |
| WO2002066071A2 (en) | 2001-01-03 | 2002-08-29 | Thomas Jefferson University | Treatment of tissue fibrosis by blocking the sp1 transcription factor |
| WO2002057480A2 (en) | 2001-01-22 | 2002-07-25 | Genta Incorporated | Cell-proliferative disorder treatments using cre decoy oligomers, bcl-2 antisense and hybrid oligomers |
| WO2002066070A1 (fr) | 2001-02-20 | 2002-08-29 | Anges Mg, Inc. | Compositions pharmaceutiques contenant un leurre et procede d'utilisation associe |
| WO2002070668A2 (en) | 2001-03-06 | 2002-09-12 | Sierra Sciences, Inc. | Methods and compositions for modulating telomerase reverse transcriptase (tert) expression |
| US20030166555A1 (en) | 2001-04-02 | 2003-09-04 | Alberini Cristina M. | Methods and compositions for regulating memory consolidation |
| EP1298141A1 (en) | 2001-09-27 | 2003-04-02 | Deutsches Krebsforschungszentrum Stiftung des öffentlichen Rechts | Interleukin-4 (IL-4) promoter sequences specifically interacting with IRF-1 and IRF-2 |
| DE10148828B4 (de) | 2001-10-04 | 2005-05-19 | Avontec Gmbh | Modulation der Expression STAT-1-abhängiger Gene |
| US6663880B1 (en) | 2001-11-30 | 2003-12-16 | Advanced Cardiovascular Systems, Inc. | Permeabilizing reagents to increase drug delivery and a method of local delivery |
| CN1697647A (zh) | 2002-02-01 | 2005-11-16 | 奥默罗斯公司 | 用于抑制疼痛,炎症和软骨退化的溶液及方法 |
| CN1240439C (zh) | 2002-03-28 | 2006-02-08 | 南京凯基生物科技发展有限公司 | 肿瘤基因开关药物 |
| JP4255123B2 (ja) | 2002-04-26 | 2009-04-15 | アンジェスＭｇ株式会社 | 転写ｄｎａ結合部位を含む環状ダンベルデコイオリゴデオキシヌクレオチド（ｃｄｏｄｎ） |
| DE10242319A1 (de) | 2002-09-12 | 2004-03-25 | Avontec Gmbh | Funkionelle Korrektur der-786C/T-Varianz des humanen eNOS-Gens |
| DE10257421A1 (de) | 2002-12-09 | 2004-07-08 | Grünenthal GmbH | Regulatorische Elemente im 5'-Bereich des VR1-Gens |
| KR20150108943A (ko) | 2002-12-09 | 2015-09-30 | 아브락시스 바이오사이언스, 엘엘씨 | 약리학적 물질의 조성물 및 그 전달방법 |
| WO2005004702A2 (en) | 2003-06-30 | 2005-01-20 | Massachusetts Institute Of Technology | Egr genes as targets for the diagnosis and treatment of schizophrenia |
| WO2005027830A2 (en) * | 2003-09-12 | 2005-03-31 | Virginia Commonwealth University | Chimeric transcription factor decoy oligonucleotides |
| JP2005336081A (ja) | 2004-05-26 | 2005-12-08 | Anges Mg Inc | Ｎｒ２ｂ−ｎｍｄａ受容体の再発現抑制剤 |
| US7482158B2 (en) | 2004-07-01 | 2009-01-27 | Mathison Brian H | Composite polynucleic acid therapeutics |
| WO2006012625A2 (en) | 2004-07-22 | 2006-02-02 | University Of Pittsburgh - Of The Commonwealth System Of Higher Education | Stat3 decoy oligonucleotides and uses therefor |
| WO2006034433A2 (en) | 2004-09-21 | 2006-03-30 | Anesiva, Inc. | Delivery of polynucleotides |
| ES2594083T3 (es) | 2004-09-28 | 2016-12-15 | Quark Pharmaceuticals, Inc. | Oligorribonucleótidos y métodos de uso de los mismos para tratamiento de la alopecia, insuficiencia renal aguda y otras enfermedades |
| CA2583576A1 (en) | 2004-10-22 | 2006-04-27 | Anges Mg, Inc. | Chimera (double) decoy |
| US7585848B2 (en) * | 2005-01-11 | 2009-09-08 | Rush University Medical Center | Methods and compositions for treating, inhibiting and reversing disorders of the intervertebral disc |
| US8268572B2 (en) * | 2005-03-04 | 2012-09-18 | Dana-Farber Cancer Institute, Inc. | Methods to identify inhibitors of Runx1-mediated expression of nociceptive receptors and ion channels |
| US7680060B2 (en) * | 2005-03-08 | 2010-03-16 | Cisco Technology, Inc. | Transferring state information in a network |
| EP1877556B1 (en) | 2005-03-25 | 2011-09-14 | Medtronic, Inc. | Use of anti-tnf or anti-il1 rnai to suppress pro- inflammatory cytokine actions locally to treat pain |
| ES2845146T3 (es) | 2006-10-09 | 2021-07-26 | Neurofluidics Inc | Sistema de purificación de líquido cefalorraquídeo |
| AU2008242842B2 (en) | 2007-04-17 | 2014-06-05 | Baxter Healthcare Sa | Nucleic acid microparticles for pulmonary delivery |
| ES2619314T3 (es) * | 2007-05-11 | 2017-06-26 | Adynxx, Inc. | Expresión génica y dolor |
| KR101606495B1 (ko) | 2010-08-20 | 2016-03-28 | 레플리코르 인코포레이티드 | 올리고뉴클레오타이드 킬레이트 복합체 |
| WO2012177906A1 (en) | 2011-06-21 | 2012-12-27 | Alnylam Pharmaceuticals, Inc. | Assays and methods for determining activity of a therapeutic agent in a subject |
| MX350463B (es) | 2011-07-20 | 2017-09-06 | Hospira Inc | Métodos de tratamiento del dolor. |
| AU2013259402B2 (en) | 2012-05-10 | 2017-12-21 | Adynxx, Inc. | Formulations for the delivery of active ingredients |
| US9492506B2 (en) | 2012-05-18 | 2016-11-15 | Replicor Inc. | Oligonucleotide chelate complex—polypeptide compositions and methods |
| PT3180434T (pt) | 2014-08-15 | 2019-10-29 | Adynxx Inc | Chamarizes oligonucleotídicos para o tratamento da dor |
| WO2017151644A1 (en) | 2016-02-29 | 2017-09-08 | Adynxx, Inc. | Compositions and methods for pain amelioration via modification of gene expression |
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