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Inhibition of microRNA functions by novel nucleic acids, iMIR

Research Project

Project/Area Number 25640090
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Tumor therapeutics
Research InstitutionOsaka University

Principal Investigator

EGUCHI Yutaka  大阪大学, 医学(系)研究科(研究院), 准教授 (20243206)

Co-Investigator(Kenkyū-buntansha) MURAKAMI Yoshiki  大阪市立大学, 大学院医学研究科, 准教授 (00397556)
Co-Investigator(Renkei-kenkyūsha) SUZUKI Hiroshi  東京大学, 大学院医学系研究科, 特任助教 (00587793)
OCHIYA Takahiro  独立行政法人国立がん研究センター, 研究所, 分野長 (60192530)
KURODA Masahiko  東京医科大学, 医学部, 教授 (80251304)
Project Period (FY) 2013-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
KeywordsiMIR / miRNA / 核酸医薬 / miR-16 / miR-21 / miR-122 / C型肝炎ウイルス / アミノ酸アミダイト
Outline of Final Research Achievements

We developed novel nucleic acid iMIR (Inhibitor of miRNA). We constructed various iMIRs targeting miR-16 and miR-21 by joining 3 miRNA-binding sequences (MBS) containing bulge-type imperfect complementarity with amino acid amidites, and found that Gly-Gly-type iMIR and TPA-type iMIR showed strong activity to inhibit miRNA functions, assessed by luciferase reporter assay. We also found that Gly-Gly-type RNA-iMIR and TPA-type RNA-iMIR targeting miR-122 strongly inhibited replication of hepatitis C virus (HCV), and 10-fold more effective than LNAs in inhibiting HCV replication. iMIR treatment of OR6 cells reduced HCV replication without inducing interferon responses or cellular toxicity, suggesting that iMIRs are promising as novel antiviral agents. These results were published in Molecular Therapy-Nucleic Acids (2015, 4, e219).

Report

(3 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • Research Products

    (4 results)

All 2015 2014 Other

All Journal Article (1 results) (of which Peer Reviewed: 1 results,  Open Access: 1 results) Presentation (3 results) (of which Invited: 1 results)

  • [Journal Article] Control of HCV Replication with iMIRs, a Novel Anti-RNAi Agent2015

    • Author(s)
      Saori Itami, Yutaka Eguchi, Takayuki Mizutani, Eriko Aoki, Tadaaki Ohgi, Masahiko Kuroda, Takahiro Ochiya, Nobuyuki Kato, Hiroshi I Suzuki, Norifumi Kawada and Yoshiki Murakami
    • Journal Title

      Molecular Therapy Nucleic Acids

      Volume: 4 Pages: e219-e219

    • DOI

      10.1038/mtna.2014.71

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] Novel RNAi agent can control HCV replication2014

    • Author(s)
      Yoshiki Murakami, Saori Itami, Takayuki Mizutani, Masahiko Kuroda, Takahiro Ochiya, Nobuyuki Kato, Yutaka Eguchi, Hiroshi Suzuki
    • Organizer
      Keystone Symposia, “RNA Silencing”
    • Place of Presentation
      Seattle, Washington USA
    • Related Report
      2013 Research-status Report
  • [Presentation] 特別企画:shRNAライブラリーの開発と細胞死関連遺伝子のスクリーニング

    • Author(s)
      惠口 豊
    • Organizer
      第5回 日本RNAi研究会年会
    • Place of Presentation
      広島
    • Related Report
      2013 Research-status Report
    • Invited
  • [Presentation] miR-122 に対するiMIR はC 型肝炎ウイルス複製抑制に効果的である

    • Author(s)
      伊丹沙織、村上善基、黒田雅彦、落谷孝広、恵口豊、河田則文
    • Organizer
      第72回日本癌学会
    • Place of Presentation
      横浜
    • Related Report
      2013 Research-status Report

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Published: 2014-07-25   Modified: 2019-07-29  

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