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Development of prodrug-siRNA activated by intracellular reducing environment

Research Project

Project/Area Number 24790121
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Drug development chemistry
Research InstitutionOsaka University of Pharmaceutical Sciences

Principal Investigator

NAKAGAWA Osamu  大阪薬科大学, 薬学部, 助手 (90380691)

Project Period (FY) 2012-04-01 – 2014-03-31
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2013: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2012: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
KeywordsRNA干渉 / siRNA / プロドラッグ / 機能性核酸 / 核酸化学
Research Abstract

In this study, we developed 2'-O-methyldithiomethyl (MDTM)-RNA as a prodrug-RNA. The MDTM-RNAs showed high stability under fetal bovine serum, and were easily converted into native-RNAs under glutathione reducing condition found in the intracellular environment. In addition, the MDTM-RNAs showed enough affinity toward complementary RNA. The synthesis of MDTM-RNAs was effectively achieved by a post-synthetic approach. The MDTM-RNA might be an excellent candidate for RNA technologies such as RNA interference.

Report

(3 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Research-status Report
  • Research Products

    (20 results)

All 2014 2013 2012

All Journal Article (1 results) (of which Peer Reviewed: 1 results) Presentation (19 results)

  • [Journal Article] A Post-Synthetic Approach for the Synthesis of 2'-O-Methyldithiomethyl-Modified Oligonucleotides Responsive to Reducing Environment2013

    • Author(s)
      Yosuke Ochi, Osamu Nakagawa, Katsunori Sakaguchi, Shun-ichi Wada, Hidehito Urata
    • Journal Title

      Chem. Commun.

      Volume: 49 Issue: 69 Pages: 7620-7622

    • DOI

      10.1039/c3cc43725f

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Presentation] オリゴ合成後修飾法の拡張を指向下2'-O-エチルジチオメチル-オリゴヌクレオチドの合成2014

    • Author(s)
      越智洋輔,中川治,和田俊一,浦田秀仁
    • Organizer
      日本薬学会第134年会
    • Place of Presentation
      熊本
    • Related Report
      2013 Final Research Report
  • [Presentation] オリゴ合成後修飾法による2'-O-メチルジチオメチル修飾RNA合成と二重鎖形成能の評価2014

    • Author(s)
      今井美恵子,坂口勝則,越智洋輔,中川治,和田俊一,浦田秀仁
    • Organizer
      日本薬学会第134年会
    • Place of Presentation
      熊本
    • Related Report
      2013 Final Research Report
  • [Presentation] オリゴ合成後修飾法の拡張を指向した2’-O-エチルジチオメチル-オリゴヌクレオチドの合成2014

    • Author(s)
      越智洋輔, 中川 治, 和田俊一, 浦田秀仁
    • Organizer
      日本薬学会第134年会
    • Place of Presentation
      熊本
    • Related Report
      2013 Annual Research Report
  • [Presentation] オリゴ合成後修飾法による2'-O-メ チルジチオメチル修飾RNA合成と二重鎖形成能の評価2014

    • Author(s)
      今井美恵子, 坂口勝則, 越智洋輔, 中川 治, 和田俊一, 浦田秀仁
    • Organizer
      日本薬学会第134年会
    • Place of Presentation
      熊本
    • Related Report
      2013 Annual Research Report
  • [Presentation] 2'-O-メチルジチオメチル修飾核酸のRNA導入とプロドラッグ分子としての機能評価2013

    • Author(s)
      中川治,越智洋輔,坂口勝則,惣坊克磨,三上友寛,和田俊一,浦田秀仁
    • Organizer
      第63回日本薬学会近畿支部総会・大会
    • Place of Presentation
      京都
    • Year and Date
      2013-10-12
    • Related Report
      2013 Final Research Report
  • [Presentation] Development of 2'-O-methyldithiomethyl-modified RNA as prodrug-siRNA : Reducing-Environment-Dependent Uncatalyzed Chemical Transforming RNA,"REDUCT-RNA"2013

    • Author(s)
      Osamu Nakagawa, Yosuke Ochi, Katunori Sakaguchi, Katsuma Sobo, Tomohiro Mikami, Shun-ichi Wada, Hidehito Urata
    • Organizer
      40^<th> International Symposium on Nucleic Acids Chemistry
    • Place of Presentation
      Yokohama, Japan
    • Related Report
      2013 Final Research Report
  • [Presentation] 2'-O-メチルジチオメチル修飾RNAのポストシンセシス法による効率的合成法の開発2013

    • Author(s)
      中川治,越智洋輔,坂口勝則,惣坊克磨,三上友寛,和田俊一,浦田秀仁
    • Organizer
      第39回反応と合成の進歩シンポジウム
    • Place of Presentation
      福岡
    • Related Report
      2013 Final Research Report
  • [Presentation] siRNAへの応用を目指したプロドラッグ型RNA分子 : 2'-O-メチルジチオメチル修飾RNAの合成2013

    • Author(s)
      中川治,越智洋輔,坂口勝則,惣坊克磨,三上友寛,和田俊一,浦田秀仁
    • Organizer
      第7回バイオ関連化学シンポジウム
    • Place of Presentation
      名古屋
    • Related Report
      2013 Final Research Report
  • [Presentation] 還元環境下でのジスルフィド結合切断に基づくプロドラッグ型人工RNA分子 : 2'-O-メチルジチオメチルRNAの開発2013

    • Author(s)
      中川治,越智洋輔,坂口勝則,惣坊克磨,三上友寛,和田俊一,浦田秀仁
    • Organizer
      日本薬学会第133年会
    • Place of Presentation
      横浜
    • Related Report
      2013 Final Research Report
  • [Presentation] siRNAへの応用を目指したプロドラッグ型RNA分子: 2'-O-メチルジチオメチル修飾RNAの合成2013

    • Author(s)
      中川 治, 越智洋輔, 坂口勝則, 惣坊克磨, 三上友寛, 和田俊一, 浦田秀仁
    • Organizer
      第7回 バイオ関連化学シンポジウム
    • Place of Presentation
      名古屋
    • Related Report
      2013 Annual Research Report
  • [Presentation] 2’-O-メチルジチオメチル修飾核酸のRNA導入とプロドラッグ分子としての機能評価2013

    • Author(s)
      中川 治, 越智洋輔, 坂口勝則, 惣坊克磨, 三上友寛, 和田俊一, 浦田秀仁
    • Organizer
      第63回 日本薬学会 近畿支部総会・大会
    • Place of Presentation
      京都
    • Related Report
      2013 Annual Research Report
  • [Presentation] 2'-O-メチルジチオメチル修飾 RNA のポストシンセシス法による効率的合成法の開発2013

    • Author(s)
      中川 治,越智洋輔,坂口勝則,惣坊克磨,三上友寛,和田俊一,浦田秀仁
    • Organizer
      第39回 反応と合成の進歩シンポジウム
    • Place of Presentation
      福岡
    • Related Report
      2013 Annual Research Report
  • [Presentation] Development of 2’-O-methyldithiomethyl-modified RNA as prodrug-siRNA: Reducing-Environment-Dependent Uncatalyzed Chemical Transforming RNA, “REDUCT-RNA”2013

    • Author(s)
      Osamu Nakagawa , Yosuke Ochi, Katsunori Sakaguchi, Katsuma Sobo, Tomohiro Mikami, Shun-ichi Wada, Hidehito Urata
    • Organizer
      40th International Symposium on Nucleic Acids Chemistry
    • Place of Presentation
      Yokohama, Japan
    • Related Report
      2013 Annual Research Report
  • [Presentation] 還元環境下でのジスルフィド結合切断に基づくプロドラッグ型 人工RNA分子: 2'-O-メチルジチオメチルRNAの開発2013

    • Author(s)
      中川 治, 越智洋輔, 坂口勝則, 惣坊克磨, 三上友寛, 和田俊一, 浦田秀仁
    • Organizer
      日本薬学会 第133年会
    • Place of Presentation
      横浜
    • Related Report
      2012 Research-status Report
  • [Presentation] 細胞内還元環境に応答し活性化するプロドラッグ型人工RNA分子の開発2012

    • Author(s)
      中川治,越智洋輔,坂口勝則,和田俊一,浦田秀仁
    • Organizer
      第62回日本薬学会近畿支部総会・大会
    • Place of Presentation
      兵庫
    • Year and Date
      2012-10-20
    • Related Report
      2013 Final Research Report
  • [Presentation] Synthesis and Evaluation of 2'-O -Methyldithiomethyl-RNA as Prodrug-RNA Activated by Reducing Environment2012

    • Author(s)
      Osamu Nakagawa, Yosuke Ochi, Katunori Sakaguchi, Shun-ichi Wada, Hidehito Urata
    • Organizer
      39^<th> International Symposium on Nucleic Acids Chemistry
    • Place of Presentation
      Nagoya, Japan
    • Related Report
      2013 Final Research Report
  • [Presentation] 合成後修飾法による2'-O-メチルジチオメチルオリゴヌクレオチドの合成2012

    • Author(s)
      越智洋輔,中川治,和田俊一,浦田秀仁
    • Organizer
      日本薬学会第132年会
    • Place of Presentation
      札幌
    • Related Report
      2013 Final Research Report
  • [Presentation] 細胞内還元環境に応答し活性化するプロドラッグ型人工RNA分子の開発2012

    • Author(s)
      中川 治, 越智洋輔, 坂口勝則, 和田俊一, 浦田秀仁
    • Organizer
      第62回 日本薬学会近畿支部総会・大会
    • Place of Presentation
      神戸
    • Related Report
      2012 Research-status Report
  • [Presentation] Synthesis and Evaluation of 2'-O-Methyldithiomethyl-RNA as Prodrug-RNA Activated by Reducing Environment2012

    • Author(s)
      Osamu Nakagawa, Yosuke Ochi, Katsunori Sakaguchi, Shun-ichi Wada, Hidehito Urata
    • Organizer
      The 39th International Symposium on Nucleic Acid Chemistry (ISNAC2012)
    • Place of Presentation
      Nagoya, Japan
    • Related Report
      2012 Research-status Report

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Published: 2013-05-31   Modified: 2019-07-29  

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