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Selection of cell penetrating peptide with evolutionary molecular engineering specialized for siRNA delivery

Research Project

Project/Area Number 17K07232
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Tumor therapeutics
Research InstitutionInstitute of Physical and Chemical Research

Principal Investigator

Tada Seiichi  国立研究開発法人理化学研究所, 創発物性科学研究センター, 研究員 (30598165)

Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords細胞膜透過ペプチド / cDNAディスプレイ / in vitro セレクション / RNAi / 細胞内導入 / 進化分子工学 / 遺伝子発現抑制 / shRNA / in vitroセレクション / siRNA / 膜透過ペプチド
Outline of Final Research Achievements

I investigated the development of evolutionary molecular engineering selection method of cell penetrating peptides (CPP) for RNAi intracellular delivery based on gene suppression efficiency. I modified the mRNA for cDNA display selection of CPP with shRNA sequence at 5’ terminus in order to select the CPP based on both of cellular uptake efficiency and gene suppression efficiency. In this study, I developed the method of preparation of shRNA-conjugated cDNA display complex and confirmed the gene expression efficiency of shRNA domain after cell transfection. However, it was also revealed that the yield of shRNA-conjugated cDNA display complex should be improved for the CPP selection using cultured cells based on gene suppression level.

Academic Significance and Societal Importance of the Research Achievements

今回の検討により、cDNAディスプレイによるペプチド選別の際に、複合体に様々な修飾を施す余地があることが確認された。今回は細胞内移行と遺伝子発現抑制に焦点を当てて検討を進めたが、今後の検討によってはcDNAディスプレイ複合体に他の低分子化合物や機能性タンパク質を連結することで、従来選別されていた特定の標的を認識するペプチドの選別のみならず、標的検出や薬物送達・薬効の高低に基づいたペプチド選別を実施する可能性が示唆される。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (3 results)

All 2019 2018

All Journal Article (2 results) (of which Peer Reviewed: 2 results) Presentation (1 results)

  • [Journal Article] Phosphorogenic and spontaneous formation of tris(bipyridine)ruthenium in peptide scaffolds2019

    • Author(s)
      Karimiavargani Marziyeh、Tada Seiichi、Minagawa Noriko、Shimizu Yoshihiro、Hirose Takuji、Ito Yoshihiro、Uzawa Takanori
    • Journal Title

      Journal of Peptide Science

      Volume: 25 Issue: 4

    • DOI

      10.1002/psc.3158

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] In vitro selection of electrochemical peptide probes using bioorthogonal tRNA for influenza virus detection2018

    • Author(s)
      K. C. Tara Bahadur、Tada Seiichi、Zhu Liping、Uzawa Takanori、Minagawa Noriko、Luo Shyh-Chyang、Zhao Haichao、Yu Hsiao-hua、Aigaki Toshiro、Ito Yoshihiro
    • Journal Title

      Chemical Communications

      Volume: 印刷中 Issue: 41 Pages: 5201-5204

    • DOI

      10.1039/c8cc01775a

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Presentation] 化学拡張型進化分子工学的手法によるインフルエンザウイルスの電気化学的検出2019

    • Author(s)
      多田 誠一、皆川 倫子、鵜澤 尊規、伊藤 嘉浩
    • Organizer
      日本分析化学会第68年会
    • Related Report
      2019 Annual Research Report

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Published: 2017-04-28   Modified: 2021-02-19  

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