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Development of RNA aptamer against membrane protein using virus-like particle

Research Project

Project/Area Number 17K20087
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Research Field Biomedical engineering and related fields
Research InstitutionThe University of Tokyo

Principal Investigator

TAKAHASHI MASAKI  東京大学, 医科学研究所, 特任准教授 (00549529)

Project Period (FY) 2017-06-30 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2018: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2017: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Keywordsアプタマー / 膜タンパク質 / virus-like particle / ウイルス様粒子 / RNAアプタマー / GPCR / 核酸 / 生物・生体工学 / ウイルス
Outline of Final Research Achievements

Here we present a novel method to generate RNA aptamer to membrane protein whose structure are stabilized with virus-like particles (VLPs). In this project, several G-protein coupled receptors (GPCRs) are used for development of the method as model targets. After optimization of the method, our assessment showed that aptamers isolated from the method can bind to target GPCR and affect their function as not only antagonist but also partial agonist. Therefore, it seemed that our method provides a novel strategy for finding affinity molecules against various membrane proteins and is useful for drug discovery.

Academic Significance and Societal Importance of the Research Achievements

膜タンパク質は細胞や生体の機能を制御する重要なタンパク質である。しかしながら、それらに特異的に結合し、活性を制御する分子の汎用的創製法は依然存在しない。本研究では、VLPと核酸抗体・RNAアプタマーを用いた新たな切り口から、創薬標的として需要の高いGPCRをモデル標的として、膜タンパク質の特異的活性制御分子の創製基盤を構築することに成功した。今後、当該技術の更なる最適化と高度化を実現することで、基礎ならびに創薬における幅広い研究分野の発展に大きく貢献することが期待できる。

Report

(3 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • Research Products

    (7 results)

All 2018

All Journal Article (3 results) (of which Peer Reviewed: 3 results,  Open Access: 2 results) Presentation (4 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] Single-round isolation of diverse RNA aptamers from a random sequence pool2018

    • Author(s)
      Imashimizu M, Takahashi M, Amano R, Nakamura Y
    • Journal Title

      Biology Methods & Protocols

      Volume: 3

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Supplemental Treatment for Huntington’s Disease with miR-132 that Is Deficient in Huntington’s Disease Brain2018

    • Author(s)
      Fukuoka Masashi、Takahashi Masaki、Fujita Hiromi、Chiyo Tomoko、Popiel H. Akiko、Watanabe Shoko、Furuya Hirokazu、Murata Miho、Wada Keiji、Okada Takashi、Nagai Yoshitaka、Hohjoh Hirohiko
    • Journal Title

      Mol. Ther. Nucleic Acids

      Volume: 11 Pages: 79-90

    • DOI

      10.1016/j.omtn.2018.01.007

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Aptamers targeting cell surface proteins2018

    • Author(s)
      Takahashi Masaki
    • Journal Title

      Biochimie

      Volume: 145 Pages: 63-72

    • DOI

      10.1016/j.biochi.2017.11.019

    • Related Report
      2018 Annual Research Report 2017 Research-status Report
    • Peer Reviewed
  • [Presentation] Generation of aptamers against GPCR by a novel SELEX employing virus-like particles (VLPs)2018

    • Author(s)
      Masaki Takahashi, Ryo Amano, Anna Martinez, Kazumasa Akita, Yoshikazu Nakamura
    • Organizer
      The Oligonucleotide Therapeutics Society
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] ウイルス様粒子を用いたGPCR結合RNAアプタマーの創製2018

    • Author(s)
      天野 亮、高橋 理貴、Anna Martinez、秋田 一雅、中村義一
    • Organizer
      日本分子生物学会年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] ミセル化GPCRを標的としたSELEX手法の開発2018

    • Author(s)
      Maritinez Anna、秋田 一雅、今井 博貴、猪股 恵美礼、高橋 理貴、天野 亮、中村 義一
    • Organizer
      日本分子生物学会年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] ウイルス様粒子を用いたGPCRアプタマー創製法の開発2018

    • Author(s)
      高橋 理貴、天野 亮、Anna Martinez、秋田 一雅、中村義一
    • Organizer
      日本分子生物学会年会
    • Related Report
      2018 Annual Research Report

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Published: 2017-07-21   Modified: 2020-03-30  

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