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Development of siRNA delivery for hematological malignancy using exosomal lipid

Research Project

Project/Area Number 17K16197
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Hematology
Research InstitutionKyoto Pharmaceutical University

Principal Investigator

Toda Yuki  京都薬科大学, 薬学部, 助教 (40779724)

Research Collaborator Ashihara Eishi  
Morita Shin-ya  
Project Period (FY) 2017-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2017: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Keywordsエクソソーム / siRNA / 血液がん / リポソーム / 血液がん細胞 / 細胞内移行 / MLL白血病 / 多発性骨髄腫 / オートクライン / 核酸医薬の送達技術
Outline of Final Research Achievements

Gene therapy using siRNA is one of the most promising strategy makes cancer therapy more effective and safer. However, development of delivery technology is essential for siRNA therapeutics which is easily degraded by nuclease in body. Notably, the incorporation of siRNA into blood cancer cells has not been achieved. In this study, we prompted to introduce siRNA into some types of blood cancer cells (multiple myeloma and acute myeloid leukemia) using their own extracellular vesicles (exosomes). Encapsulation of siRNA into exosomes promoted their internalization into cells, while it was not enough amount to induce RNA interference. Enhancement of the efficacy of exosome incorporation into cells and siRNA loading into exosomes could be required to solve this problem.

Academic Significance and Societal Importance of the Research Achievements

狙った分子へ特異的に作用するsiRNA製剤は、現在使用されているがん治療薬よりも安全性が極めて高いと言われている。siRNAは細胞内に移行することで作用を発揮するが、血液がん細胞に対してsiRNAを細胞内導入する技術は未だ開発されていない。本研究では、血液がん細胞株が分泌する顆粒(エクソソーム)にsiRNAを包み込ませることにより、分泌元の血液がん細胞内に送達させることに成功した。本成果は、血液がんに対するsiRNA製剤の開発に繋がる重要な知見である。

Report

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

    (13 results)

All 2018 2017 Other

All Journal Article (1 results) (of which Peer Reviewed: 1 results,  Open Access: 1 results) Presentation (10 results) (of which Int'l Joint Research: 1 results,  Invited: 3 results) Remarks (2 results)

  • [Journal Article] Multiple myeloma cells adapted to long-exposure of hypoxia exhibit stem cell characters with TGF-β/Smad pathway activation2018

    • Author(s)
      Nakagawa Yoko、Ashihara Eishi、Yao Hisayuki、Yokota Asumi、Toda Yuki、Miura Yasuo、Nakata Susumu、Hirai Hideyo、Maekawa Taira
    • Journal Title

      BBRC

      Volume: 496 Issue: 2 Pages: 490-496

    • DOI

      10.1016/j.bbrc.2018.01.034

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] DJ-1 regulates stem cell function in glioblastoma2018

    • Author(s)
      Yuki Toda, Masao Itahara, Eishi Ashihara
    • Organizer
      The 77th Annual Meeting of the Japanese Cancer Association
    • Related Report
      2018 Annual Research Report
  • [Presentation] DJ-1は神経膠芽種幹細胞の維持に寄与する2018

    • Author(s)
      戸田侑紀、吉村亮介、板原多勇、宇野智子、中田晋、山田佳菜枝、今井悠莉、高田和幸、芦原英司
    • Organizer
      次世代を担う創薬・医療薬理シンポジウム2018
    • Related Report
      2018 Annual Research Report
  • [Presentation] 神経膠芽種幹細胞におけるDJ-1の機能2018

    • Author(s)
      戸田侑紀、吉村亮介、板原多勇、宇野智子、中田晋、山田佳菜枝、今井悠莉、高田和幸、芦原英司
    • Organizer
      生体機能と創薬シンポジウム2018
    • Related Report
      2018 Annual Research Report
  • [Presentation] 生体内の情報伝達顆粒を利用した腫瘍標的化技術の開発2018

    • Author(s)
      戸田侑紀
    • Organizer
      KYOTO BASIC SCIENCE FORUM
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] The role of DJ-1 in cancer stem cells2018

    • Author(s)
      Yuki Toda
    • Organizer
      京都 Cancer Biology セミナー
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Exosomesの指向性を利用した薬物送達技術の開発2018

    • Author(s)
      戸田侑紀
    • Organizer
      第23回大文字クラブ
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] Cancer targeting using exosomal lipids toward detection enhancement of microlesion2018

    • Author(s)
      Yuki Toda, Hikaru Kawakami, Saeka Ukai, Shin-ya Morita, Kazuyuki Takata, Eishi Ashihara
    • Organizer
      3rd AACR-SNMMI Joint Conference on State-of-the-Art Molecular Imaging in Cancer Biology and Therapy
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] エクソソーム膜脂質より再構成したリポソームのがん細胞移行性評価2017

    • Author(s)
      鵜飼幸永佳、戸田侑紀、川上 光、高田和幸、芦原英司
    • Organizer
      日本薬学会第137年会
    • Related Report
      2017 Research-status Report
  • [Presentation] 細胞外小胞の脂質組成から見出した新規がん標的型DDS2017

    • Author(s)
      戸田侑紀、芦原英司
    • Organizer
      第21回日本がん分子標的治療学会学術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] 細胞指向性を制御するエクソソームの脂質と薬物送達への応用2017

    • Author(s)
      戸田侑紀、川上 光、鵜飼幸永佳、森田真也、高田和幸、芦原英司
    • Organizer
      第11回次世代を担う若手医療薬科学シンポジウム2017
    • Related Report
      2017 Research-status Report
  • [Remarks] 京都薬科大学病態生理学分野ホームページ

    • URL

      http://labo.kyoto-phu.ac.jp/seiri/seiri-j.html

    • Related Report
      2018 Annual Research Report
  • [Remarks] 京都薬科大学・病態生理学分野のホームページ

    • URL

      http://labo.kyoto-phu.ac.jp/seiri/seiri-j.html

    • Related Report
      2017 Research-status Report

URL: 

Published: 2017-04-28   Modified: 2020-03-30  

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