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Development of in vivo gene therapy using exosomes loading immunomodulatory molecules

Research Project

Project/Area Number 18H02562
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 47020:Pharmaceutical analytical chemistry and physicochemistry-related
Research InstitutionKyoto University

Principal Investigator

Takakura Yoshinobu  京都大学, 薬学研究科, 教授 (30171432)

Co-Investigator(Kenkyū-buntansha) 高橋 有己  京都大学, 薬学研究科, 准教授 (00547870)
Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2020: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2019: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥7,410,000 (Direct Cost: ¥5,700,000、Indirect Cost: ¥1,710,000)
Keywordsエキソソーム / ルシフェラーゼ / 免疫療法 / サイトカイン / 免疫 / 内因性
Outline of Final Research Achievements

In this study, we analyzed the behavior of endogenous exosomes and developed a method to attach immunoregulatory molecules to exosomes in order to develop in vivo gene immunotherapy using endogenous exosomes produced in the body. We focused on blood exosomes as endogenous exosomes, and succeeded in establishing a method to collect and label them. We selected NBD peptide, an NF-κB inhibitory peptide, as an immunoregulatory molecule, and succeeded in developing an efficient method for loading NBD peptide into exosomes. The NBD peptide-loaded exosomes showed a high anti-inflammatory effect. In conclusion, we have succeeded in establishing the basis for in vivo gene immunotherapy using endogenous exosomes.

Academic Significance and Societal Importance of the Research Achievements

細胞から産生される粒子径100nm程度の膜小胞であるエキソソームは、細胞間で物質輸送を行う輸送担体であり、その生理機能の解明とそれを利用した治療法の開発が期待される。本研究では、体内におけるエキソソームの挙動の解明と治療用分子の搭載方法の確立に成功したが、これはエキソソームの生理機能の解明を目的とした研究並びに治療法の開発において重要な知見を提供するものである。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Annual Research Report
  • 2018 Annual Research Report
  • Research Products

    (12 results)

All 2020 2019 2018

All Journal Article (5 results) (of which Peer Reviewed: 5 results,  Open Access: 1 results) Presentation (7 results) (of which Int'l Joint Research: 2 results,  Invited: 1 results)

  • [Journal Article] Intracellular delivery of NF-κB inhibitor peptide utilizing small extracellular vesicles for the application of anti-inflammatory therapy.2020

    • Author(s)
      Takenaka M, Takahashi Y, Takakura Y.
    • Journal Title

      J Control Release.

      Volume: 328 Pages: 435-443

    • DOI

      10.1016/j.jconrel.2020.09.001

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Development of CD40L-modified tumor small extracellular vesicles for the effective induction of anti-tumor immune response.2020

    • Author(s)
      Liu W, Takahashi Y, Morishita M, Nishikawa M, Takakura Y.
    • Journal Title

      Nanomedicine (Lond).

      Volume: 15 Issue: 17 Pages: 1641-1652

    • DOI

      10.2217/nnm-2020-0071

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Antitumor immunity by small extracellular vesicles collected from activated dendritic cells through effective induction of cellular and humoral immune responses2020

    • Author(s)
      Matsumoto Akihiro、Asuka Maho、Takahashi Yuki、Takakura Yoshinobu
    • Journal Title

      Biomaterials

      Volume: 252 Pages: 120112-120112

    • DOI

      10.1016/j.biomaterials.2020.120112

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Blood concentrations of small extracellular vesicles are determined by a balance between abundant secretion and rapid clearance.2019

    • Author(s)
      Matsumoto A, Takahashi Y, Chang HY, Wu YW, Yamamoto A, Ishihama Y, Takakura Y.
    • Journal Title

      J Extracell Vesicles

      Volume: 9 Issue: 1 Pages: 1696517-1696517

    • DOI

      10.1080/20013078.2019.1696517

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Preservation of exosomes at room temperature using lyophilization.2018

    • Author(s)
      Charoenviriyakul C, Takahashi Y, Nishikawa M, Takakura Y.
    • Journal Title

      Int J Pharm.

      Volume: 553 Issue: 1-2 Pages: 1-7

    • DOI

      10.1016/j.ijpharm.2018.10.032

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Presentation] 抗炎症治療を目的とした細胞外小胞によるマクロファージへのIL4デリバリー2020

    • Author(s)
      竹中美佐子、高橋有己、薮田文寧、高倉喜信
    • Organizer
      第36回日本DDS学会学術集会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 血液中の内因性エキソソームの挙動解析のための標識法開発と薬物速度論的解析に基づく内因性エキソソーム濃度維持機構の解明2019

    • Author(s)
      松本明宏、高橋有己、山本晶、高倉喜信
    • Organizer
      日本薬剤学会第34年会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 免疫活性化能を有する抗原搭載樹状細胞由来エキソソームを利用した効果的ながんワクチン療法の開発2019

    • Author(s)
      飛鳥真帆、松本明宏、高橋有己、高倉喜信
    • Organizer
      日本薬剤学会第34年会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Development of Interferon γ-loaded tumor cell-derived extracellular vesicles applicable to cancer vaccine therapy.2019

    • Author(s)
      Nakagawa N, Takahashi Y, Takakura Y.
    • Organizer
      International Society for Extracellular Vesicles 2019
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] がんワクチン療法への適用を目的としたInterferon-γ搭載がん細胞由来exosome の開発2019

    • Author(s)
      仲川直輝, 高橋有己, 高倉喜信
    • Organizer
      に翻訳学会第139年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Development of Exosome Assembly Formed by Utilization of DNA Hybridization and its Application for Cancer Vaccine.2018

    • Author(s)
      Matsumoto A, Takahashi Y, Ariizumi R, Nishikawa M, Takakura Y.
    • Organizer
      Globalization of Pharmaceutics Education Network 2018 (GPEN2018)
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] エクソソームの標識技術とドラッグデリバリー応用の最前線2018

    • Author(s)
      高倉喜信
    • Organizer
      第36回物性物理化学研究会
    • Related Report
      2018 Annual Research Report
    • Invited

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Published: 2018-04-23   Modified: 2022-01-27  

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