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Development of novel therapeutic approach for aneurysm using decoy oligodeoxynucleotide with a ribbon-shaped circular structure.

Research Project

Project/Area Number 20590251
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field General pharmacology
Research InstitutionOsaka University

Principal Investigator

MIYAKE Takashi  Osaka University, 連合小児発達学研究科, 寄附講座特任助教 (40219746)

Co-Investigator(Kenkyū-buntansha) TANIYAMA Yoshiaki  大阪大学, 大学院・医学系研究科, 寄附講座准教授 (60372611)
Project Period (FY) 2008 – 2010
Project Status Completed (Fiscal Year 2010)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2010: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2009: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2008: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywords核酸医薬 / 動脈瘤 / デコイ
Research Abstract

We modified decoy oligodeoxynucleotide (ODN) against NFKB and ets, to a ribbon-shaped circular structure, to increase its stability for systemic administration. Intraperitoneal administration of ribbon-type decoy ODNs (R-ODNs) was performed in an elastase-induced rat aneurysm model. Treatment with chimeric R-ODN significantly inhibited aortic dilatation accompanied by a reduction of secretion of several proteases from macrophages. In contrast, conventional phosphorothioate decoy ODN failed to prevent aneurysm formation. In addition, we investigated the effect of intravenous injection of modified R-ODN against NFKB in a mouse aneurysm model. Treatment with modified R-ODN showed a tendency to decrease the size of AAA. Further modification of the decoy strategy would provide a means of less invasive molecular therapy for human AAA.

Report

(4 results)
  • 2010 Annual Research Report   Final Research Report ( PDF )
  • 2009 Annual Research Report
  • 2008 Annual Research Report
  • Research Products

    (12 results)

All 2011 2010 2009 2008

All Journal Article (4 results) (of which Peer Reviewed: 4 results) Presentation (6 results) Book (2 results)

  • [Journal Article] Systemic Administration of Ribbon-type Decoy Oligodeoxynucleotide Against Nuclear Factor κB and Ets Prevents Abdominal Aortic Aneurysm in Rat Model.2011

    • Author(s)
      Miyake T, Aoki M, et al.
    • Journal Title

      Molecular Therapy. 19

      Pages: 181-187

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Systemic Administration of Ribbon-type Decoy Oligodeoxynucleotide Against Nuclear Factor kB and Ets Prevents Abdominal Aortic Aneurysm in Rat Model.2011

    • Author(s)
      Miyake T, et al.
    • Journal Title

      Molecular Therapy

      Volume: 19 Pages: 181-187

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Pharmacological treatment of abdominal aortic aneurysm.2009

    • Author(s)
      Miyake T, Morishita R.
    • Journal Title

      Cardiovascular Research. 83

      Pages: 436-443

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Pharmacological treatment of abdominal aortic aneurysm2009

    • Author(s)
      Miyake T, et al.
    • Journal Title

      Cardiovascular Research 83

      Pages: 436-443

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Presentation] Intra-peritoneal Application of Ribbon-type Decoy Oligodeoxynucleotides against NFkB and ets Prevents Aneurysm Foemation in Rats.2010

    • Author(s)
      三宅隆, et al.
    • Organizer
      23^<RD> scientific meeting of the international society of hypertension.
    • Place of Presentation
      Vancouver, Canada.
    • Year and Date
      2010-09-29
    • Related Report
      2010 Final Research Report
  • [Presentation] Intra-peritoneal Application of Ribbon-type Decoy Oligodeoxynucl eotides against NFkB and ets Prevents Aneurysm Foemation in Rats2010

    • Author(s)
      Miyake T, et al.
    • Organizer
      23^<RD> scientific meeting of the international society of hypertension
    • Place of Presentation
      Vancouver, Canada
    • Year and Date
      2010-09-29
    • Related Report
      2010 Annual Research Report
  • [Presentation] 核酸医薬を用いた腹部大動脈瘤の低侵襲治療2009

    • Author(s)
      三宅隆, 他
    • Organizer
      第109回日本外科学会定期学術集会
    • Place of Presentation
      福岡国際会議場(福岡)
    • Year and Date
      2009-04-04
    • Related Report
      2010 Final Research Report
  • [Presentation] 核酸医薬を用いた腹部大動脈瘤の低侵襲治療2009

    • Author(s)
      三宅隆, 他
    • Organizer
      第109回 日本外科学会定期学術集会
    • Place of Presentation
      福岡国際会議場 (福岡)
    • Year and Date
      2009-04-04
    • Related Report
      2009 Annual Research Report
  • [Presentation] Inhibition of aneurysm development by intra-peritoneal application of ribbon-type decoy oligodeoxynucleotide against nuclear factor-κB and ets in a rat model.2008

    • Author(s)
      三宅隆, et al.
    • Organizer
      American Heart Association.
    • Place of Presentation
      New Orleans, USA.
    • Year and Date
      2008-11-09
    • Related Report
      2010 Final Research Report
  • [Presentation] Inhibition of aneurysm development by intra-peri toneal application of ribbon-type decoy oligodeoxynucleotide against nuclearfactor-κB and ets in a rat model2008

    • Author(s)
      三宅 隆
    • Organizer
      American Heart Association 2008
    • Place of Presentation
      New Orleans、USA
    • Year and Date
      2008-11-09
    • Related Report
      2008 Annual Research Report
  • [Book] Annual Review 2011循環器2011

    • Author(s)
      三宅隆、森下竜一
    • Publisher
      中外医学社
    • Related Report
      2010 Final Research Report
  • [Book] Annual Review 2011 循環器2011

    • Author(s)
      三宅隆
    • Publisher
      中外医学社
    • Related Report
      2010 Annual Research Report

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Published: 2008-04-01   Modified: 2016-04-21  

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