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Development of novel form of mimic microRNA for microRNA replacement therapy.

Research Project

Project/Area Number 15K08410
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Experimental pathology
Research InstitutionTokyo Medical University

Principal Investigator

OHNO Shinichiro  東京医科大学, 医学部, 講師 (90513680)

Co-Investigator(Kenkyū-buntansha) 熊谷 勝義  東京医科大学, 医学部, 助教 (20567911)
黒田 雅彦  東京医科大学, 医学部, 主任教授 (80251304)
原田 裕一郎  東京医科大学, 医学部, 助手 (80570168)
Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords核酸医薬 / microRNA / miR-34a / 肺がん / 炎症性サイトカイン
Outline of Final Research Achievements

The innate cytokine response to nucleic acid is the most challenging problem confronting the practical use of nucleic acid medicine. The degree of stimulation of the innate cytokine response strongly depends on the length of the nucleic acid. In this study, we developed a 30-nucleotide single strand RNA, termed "guide hairpin RNA (ghRNA, ghR)", that has a physiological function similar to that of miRNA and siRNA. The ghR caused no innate cytokine response either in vitro or in vivo. In addition, its structure does not contain a passenger strand seed sequence, reducing the unwanted gene repression relative to existing short RNA reagents. Systemic and local injection of ghR-form miR-34a (ghR-34a) suppressed tumor growth in a mouse model of RAS-induced lung cancer. This novel RNA interference (RNAi) technology may provide a novel, safe, and effective nucleic acid drug platform that will increase the clinical usefulness of nucleic acid therapy.

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (9 results)

All 2017 2016 2015

All Journal Article (2 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 2 results,  Open Access: 1 results,  Acknowledgement Compliant: 1 results) Presentation (7 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] Development of novel small hairpin RNAs that do not require processing by dicer or AGO22016

    • Author(s)
      Ohno S, Itano K, Harada Y, Asada K, Oikawa K, Kashiwazako M, Okuyama H, Kumagai K, Takanashi M, Sudo K, Ikeda N, Kuroda M.
    • Journal Title

      Mol Ther

      Volume: 24 Issue: 7 Pages: 1278-1289

    • DOI

      10.1038/mt.2016.81

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Focus on Extracellular Vesicles: Development of Extracellular Vesicle-Based Therapeutic Systems.2016

    • Author(s)
      Ohno S, Drummen G, Kuroda M.
    • Journal Title

      Int. J. Mol. Sci.

      Volume: 17(2) Issue: 2 Pages: 172-191

    • DOI

      10.3390/ijms17020172

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] RNA干渉に働く短鎖ヘアピンRNAの探索と機能解析2017

    • Author(s)
      大野慎一郎、原田裕一郎、村上善基、黒田雅彦
    • Organizer
      第106回日本病理学会総会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Search and characterization of novel hairpin RNAs acting on RNA interference2017

    • Author(s)
      大野慎一郎、原田裕一郎、村上善基、黒田雅彦
    • Organizer
      第6回医薬工シンポジウム
    • Related Report
      2017 Annual Research Report
  • [Presentation] Up-regulation of BLU tumor suppressor by miR-34a.2017

    • Author(s)
      三部芳裕、大野慎一郎、黒田雅彦
    • Organizer
      第9回日本RNAi研究会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Mir-34aによるがん抑制遺伝子BLUの発現制御機構2017

    • Author(s)
      大野慎一郎、三部芳裕、弓野梨紗、老川桂生、原田裕一郞、黒田雅彦
    • Organizer
      第76回日本癌学会学術総会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Development of novel Dicer- and Ago2-independent small hairpin RNAs.2016

    • Author(s)
      Shin-ichiro OHNO, Karen ITANO, Yuichirou HARADA, Koutaro ASADA, Keiki OIKAWA, Mikie KASHIWAZAKO, Hikaru OKUYAMA, Katsuyoshi KUMAGAI, Masakatsu TAKANASHI, Katsuko SUDO, Norihiko IKEDA, Masahiko KURODA.
    • Organizer
      ASGCT 19th Annual Meeting 2016
    • Place of Presentation
      Marriott Wardman Park, Washington, DC, USA.
    • Year and Date
      2016-05-04
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] 副作用を軽減した短鎖型核酸医薬の開発2015

    • Author(s)
      大野慎一郎、板野華連、浅田浩太朗、老川桂生、柏迫幹絵、高梨正勝、黒田雅彦
    • Organizer
      第7回日本RNAi研究会
    • Place of Presentation
      広島プリンスホテル
    • Year and Date
      2015-08-26
    • Related Report
      2015 Research-status Report
  • [Presentation] 肺がん治療を想定した副作用の少ない短鎖型新規核酸医薬の開発2015

    • Author(s)
      大野慎一郎、板野華連、原田裕一郎、浅田浩太朗、老川桂生、柏迫幹絵、高梨正勝、須藤カツ子、池田徳彦、黒田雅彦
    • Organizer
      第104回日本病理学会総会
    • Place of Presentation
      名古屋国際会議場
    • Year and Date
      2015-04-30
    • Related Report
      2015 Research-status Report

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Published: 2015-04-16   Modified: 2019-03-29  

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