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Development of RNase H-mediated antiviral oligonucleotides.

Research Project

Project/Area Number 18K14595
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 42020:Veterinary medical science-related
Research InstitutionNihon University

Principal Investigator

ECHIGOYA Yusuke  日本大学, 生物資源科学部, 講師 (90609950)

Project Period (FY) 2018-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Keywordsアンチセンス核酸 / RNA分解 / 日本脳炎 / ウイルスRNA / gapmer / 核酸医薬 / RNA / ウイルス / 抗ウイルス薬
Outline of Final Research Achievements

Antisense oligonucleotides (ASO) to induce RNase H-mediated degradation of target RNA, called ASO gapmer, are expected to be novel antiviral therapeutics. The present study revealed that ASO gapmer effectively inhibits the proliferation of the Japanese encephalitis virus (JEV) in vitro. The result showed that the antiviral effects of ASO gapmer are caused in a sequence- and chemistry-dependent manner. The findings could facilitate the development of antiviral oligonucleotide therapeutics against not only JEV but also other flavivirus species representing public health threats, such as dengue virus, Zika virus, West Nile virus, and yellow fever virus.

Academic Significance and Societal Importance of the Research Achievements

DNA/RNA様の修飾核酸からなるアンチセンス核酸(ASO)はRNAを標的とする新たな創薬シーズとして期待されている。しかし、ASOのウイルスRNAに対する有効性や作用メカニズムについては不明な点が多い。本研究ではASO gapmerの日本脳炎ウイルス(JEV) RNAに対する特異的な分解作用が明らかとなり、ASO gapmerが抗ウイルス薬として応用できる可能性が示された。本知見は、日本脳炎のみならず特効薬の開発が困難なウイルス感染症に対する新たな治療コンセプトの確立に貢献するものと考えられる。

Report

(5 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (16 results)

All 2022 2021 2020 2019 2018 Other

All Int'l Joint Research (1 results) Journal Article (9 results) (of which Int'l Joint Research: 8 results,  Peer Reviewed: 8 results,  Open Access: 4 results) Presentation (3 results) (of which Invited: 1 results) Remarks (3 results)

  • [Int'l Joint Research] アルバータ大学(カナダ)

    • Related Report
      2018 Research-status Report
  • [Journal Article] Development of DG9 peptide-conjugated single- and multi-exon skipping therapies for the treatment of Duchenne muscular dystrophy2022

    • Author(s)
      Lim KRQ, Woo S, Melo D, Huang Y, Dzierlega K, Shah MNA, Aslesh T, Roshmi RR, Echigoya Y, Maruyama R, Moulton HM, Yokota T.
    • Journal Title

      Proc Natl Acad Sci U S A.

      Volume: 119(9) Issue: 9

    • DOI

      10.1073/pnas.2112546119

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] A Dystrophin Exon-52 Deleted Miniature Pig Model of Duchenne Muscular Dystrophy and Evaluation of Exon Skipping2021

    • Author(s)
      Echigoya Y, Trieu N, Duddy W, Moulton HM, Yin H, Partridge TA, Hoffman EP, Kornegay JN, Rohret FA, Rogers CS, Yokota T.
    • Journal Title

      Int J Mol Sci.

      Volume: 22(23) Issue: 23 Pages: 13065-13065

    • DOI

      10.3390/ijms222313065

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] DUX4 Transcript Knockdown with Antisense 2′-O-Methoxyethyl Gapmers for the Treatment of Facioscapulohumeral Muscular Dystrophy2021

    • Author(s)
      Lim KRQ, Bittel A, Maruyama R, Echigoya Y, Nguyen Q, Huang Y, Dzierlega K, Zhang A, Chen YW, Yokota T.
    • Journal Title

      Molecular Therapy

      Volume: 29 Issue: 2 Pages: 848-858

    • DOI

      10.1016/j.ymthe.2020.10.010

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Inhibition of DUX4expression with antisense LNA gapmers as a therapy for facioscapulohumeral muscular dystrophy2020

    • Author(s)
      Lim KRQ, Maruyama R, Echigoya Y, Nguyen Q, Zhang A, Khawaja H, Sen Chandra S, Jones T, Jones P, Chen YW, Yokota T.
    • Journal Title

      Proceedings of the National Academy of Sciences

      Volume: 117 Issue: 28 Pages: 16509-16515

    • DOI

      10.1073/pnas.1909649117

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Amelioration of intracellular Ca2+ regulation by exon-45 skipping in Duchenne muscular dystrophy-induced pluripotent stem cell-derived cardiomyocytes.2019

    • Author(s)
      Sato M, Shiba N, Miyazaki D, Shiba Y, Echigoya Y, Yokota T, Takizawa H, Aoki Y, Takeda S, Nakamura A.
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 520 Issue: 1 Pages: 179-185

    • DOI

      10.1016/j.bbrc.2019.09.095

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Exons 45-55 Skipping Using Mutation-Tailored Cocktails of Antisense Morpholinos in the DMD Gene2019

    • Author(s)
      Echigoya Yusuke、Lim Kenji Rowel Q.、Melo Dyanna、Bao Bo、Trieu Nhu、Mizobe Yoshitaka、Maruyama Rika、Mamchaoui Kamel、Tanihata Jun、Aoki Yoshitsugu、Takeda Shin’ichi、Mouly Vincent、Duddy William、Yokota Toshifumi
    • Journal Title

      Molecular Therapy

      Volume: 27 Issue: 11 Pages: 2005-2017

    • DOI

      10.1016/j.ymthe.2019.07.012

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] ウイルス性疾患に対するアンチセンス核酸医薬品の開発現状と課題2019

    • Author(s)
      越後谷 裕介
    • Journal Title

      Medical Science Digest-核酸医薬の最前線-

      Volume: 1 Pages: 8-9

    • Related Report
      2018 Research-status Report
  • [Journal Article] Efficacy of Multi-exon Skipping Treatment in Duchenne Muscular Dystrophy Dog Model Neonates.2019

    • Author(s)
      Lim KRQ*, Echigoya Y* (* equally contributed), Nagata T, Kuraoka M, Kobayashi M, Aoki Y, Partridge T, Maruyama R, Takeda S, Yokota T.
    • Journal Title

      Molecular Therapy

      Volume: 27(1) Issue: 1 Pages: 76-86

    • DOI

      10.1016/j.ymthe.2018.10.011

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Multiple Exon Skipping in the Duchenne Muscular Dystrophy Hot Spots: Prospects and Challenges2018

    • Author(s)
      Echigoya Yusuke、Lim Kenji Rowel Q.、Nakamura Akinori、Yokota Toshifumi
    • Journal Title

      Journal of Personalized Medicine

      Volume: 8 Issue: 4 Pages: 41-41

    • DOI

      10.3390/jpm8040041

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] RNA分解型アンチセンス人工核酸による日本脳炎ウイルス増殖抑制効果2021

    • Author(s)
      岡本俊輔、越後谷裕介、瀬川太雄、佐藤雪太、伊藤琢也
    • Organizer
      第68回日本ウイルス学会学術集会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 日本脳炎ウイルスに増殖抑制効果を示すRNA構造阻害型アンチセンス人工核酸の開発2021

    • Author(s)
      速水李誉、越後谷裕介、岡本俊輔、伊藤琢也、佐藤雪太
    • Organizer
      第164回日本獣医学会学術集会
    • Related Report
      2021 Annual Research Report
  • [Presentation] デュシェンヌ型筋ジストロフィーに対するアンチセンス核酸カクテル療法の開発2019

    • Author(s)
      越後谷 裕介
    • Organizer
      日本筋学会 第5回学術集会 シンポジウム1「最新ゲノム解析による遺伝学的診断と運動器疾患の新たな治療戦略」
    • Related Report
      2019 Research-status Report
    • Invited
  • [Remarks] 日本大学動物医科学研究センター

    • URL

      https://hp.brs.nihon-u.ac.jp/~nuvercwp/

    • Related Report
      2021 Annual Research Report
  • [Remarks] 日本大学生物資源科学部 動物医科学研究センター

    • URL

      http://hp.brs.nihon-u.ac.jp/~nuverc/

    • Related Report
      2019 Research-status Report
  • [Remarks] 日本大学生物資源科学部 動物医科学研究センター

    • URL

      http://hp.brs.nihon-u.ac.jp/~nuverc/

    • Related Report
      2018 Research-status Report

URL: 

Published: 2018-04-23   Modified: 2023-01-30  

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