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Development of cell-specific exosome isolation method by genetic modification

Research Project

Project/Area Number 18K19315
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 43:Biology at molecular to cellular levels, and related fields
Research InstitutionNational Institute of Health Sciences

Principal Investigator

Ono Ryuichi  国立医薬品食品衛生研究所, 毒性部, 室長 (10401358)

Project Period (FY) 2018-06-29 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
Fiscal Year 2020: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2019: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2018: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Keywordsエクソソーム / 細胞外小胞 / EV
Outline of Final Research Achievements

The purpose of this study is to identify cells that secrete exosomes by inserting timing- and site-specific surface proteins into the surface of exosomes, known as extracellular vesicles, and identifying the origin of exosomes by purifying the timing- and site-specific surface proteins. We have succeeded in generating mice lacking endogenous CD9 by genome editing, and in constructing a system that expresses CD9-EGFP, a fusion of human CD9 and EGFP, in a timing- and site-specific manner and even generated chimeric transgenic mice using ES cells transfected with this system. But, all chimeric mice were found to be infertile due to impaired spermatogenesis. It is possible that the omission of CD9-EGFP expression affected spermatogenesis.

Academic Significance and Societal Importance of the Research Achievements

本研究成果により、血液採取を行ない、エクソソーム RNA を解析することで、化学物質暴露により障害を受けた細胞を同定することを可能とする基盤技術の開発を行う研究である。 本研究は高感度な有害性評価系の構築を企図しており、従来法に比較 してより短期間により少数の動物での評価が可能となると考えられる。

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

    (29 results)

All 2021 2020 2019 2018

All Journal Article (10 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 8 results,  Open Access: 8 results) Presentation (19 results) (of which Int'l Joint Research: 11 results,  Invited: 11 results)

  • [Journal Article] PEG10 viral aspartic protease domain is essential for the maintenance of fetal capillary structure in the mouse placenta2021

    • Author(s)
      Hirosuke Shiura, Ryuichi Ono, Saori Tachibana, Takashi Kohda, Tomoko Kaneko-Ishino and Fumitoshi Ishino
    • Journal Title

      Development

      Volume: 148 Issue: 19 Pages: 1-7

    • DOI

      10.1242/dev.199564

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Cell Cycle Regulation and DNA Damage Response Networks in Diffuse- and Intestinal-Type Gastric Cancer2021

    • Author(s)
      Tanabe Shihori、Quader Sabina、Ono Ryuichi、Cabral Horacio、Aoyagi Kazuhiko、Hirose Akihiko、Yokozaki Hiroshi、Sasaki Hiroki
    • Journal Title

      Cancers

      Volume: 13 Issue: 22 Pages: 5786-5786

    • DOI

      10.3390/cancers13225786

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Diverse unintended on-target mutations induced by zygote genome-editing using CRISPR/Cas9 system2021

    • Author(s)
      Igarashi Toshime、Yasuhiko Yukuto、Ono Ryuichi、Tachihara Erika、Uchiyama Miki、Takagi Atsuya、Takahashi Yu、Kuwagata Makiko、Kitajima Satoshi
    • Journal Title

      Fundamental Toxicological Sciences

      Volume: 8 Issue: 5 Pages: 161-167

    • DOI

      10.2131/fts.8.161

    • NAID

      130008111944

    • ISSN
      2189-115X
    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Novel hepatotoxicity biomarkers of extracellular vesicle (EV)-associated miRNAs induced by CCl42020

    • Author(s)
      Ono Ryuichi、Yoshioka Yusuke、Furukawa Yusuke、Naruse Mie、Kuwagata Makiko、Ochiya Takahiro、Kitajima Satoshi、Hirabayashi Yoko
    • Journal Title

      Toxicology Reports

      Volume: 7 Pages: 685-692

    • DOI

      10.1016/j.toxrep.2020.05.002

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Interplay of EMT and CSC in Cancer and the Potential Therapeutic Strategies2020

    • Author(s)
      Tanabe Shihori、Quader Sabina、Cabral Horacio、Ono Ryuichi
    • Journal Title

      Frontiers in Pharmacology

      Volume: 11 Pages: 1-8

    • DOI

      10.3389/fphar.2020.00904

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Molecular Network Profiling in Intestinal- and Diffuse-Type Gastric Cancer.2020

    • Author(s)
      Tanabe S, Quader S, Ono R, Cabral H, Aoyagi K, Hirose A, Yokozaki H, Sasaki H
    • Journal Title

      Cancers

      Volume: 12 Issue: 12 Pages: 3833-3833

    • DOI

      10.3390/cancers12123833

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] ゲノム編集技術を用いた遺伝子治療の規制と安全性評価2019

    • Author(s)
      内田恵理子、山下拓真、小野竜一、内藤雄樹、井上貴雄
    • Journal Title

      医薬品医療機器レギュラトリーサイエンス

      Volume: 50 (9) Pages: 513-522

    • NAID

      40022022270

    • Related Report
      2019 Research-status Report
  • [Journal Article] ゲノム編集技術を用いた遺伝子治療の開発動向2019

    • Author(s)
      内田恵理子、平松直人、犬飼直人、岩井謙一、渡辺武志、川崎秀吉、田村幸太朗、土屋貴穂、吉見英治、高橋則彦、伊藤辰哉、藤本和則、山下晃人、小野貴士、高木観、小野竜一、内藤雄樹、井上貴雄
    • Journal Title

      医薬品医療機器レギュラトリーサイエンス

      Volume: 50 (8) Pages: 443-453

    • NAID

      40021992942

    • Related Report
      2019 Research-status Report
  • [Journal Article] Exosome-mediated horizontal gene transfer occurs in double-strand break repair during genome editing2019

    • Author(s)
      Ono Ryuichi、Yasuhiko Yukuto、Aisaki Ken-ichi、Kitajima Satoshi、Kanno Jun、Hirabayashi Yoko
    • Journal Title

      Communications Biology

      Volume: 2 Issue: 1 Pages: 57-57

    • DOI

      10.1038/s42003-019-0300-2

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] The gene and microRNA networks of stem cells and reprogramming2018

    • Author(s)
      Tanabe Shihori, Ryuichi Ono
    • Journal Title

      AIMS Cell and Tissue Engineering

      Volume: 2 Issue: 4 Pages: 238-245

    • DOI

      10.3934/celltissue.2018.4.238

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] ゲノム編集技術の安全性評価2021

    • Author(s)
      小野竜一
    • Organizer
      第50回日本環境変異原ゲノム学会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] Novel hepatotoxicity biomarkers of exosomal miRNAs acutely induced by CCl42021

    • Author(s)
      Ryuichi Ono
    • Organizer
      アジア毒性学会学術年会
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] エクソソームが媒介したレトロトランスポゾンの 遺伝子水平遺伝による哺乳類の誕生2021

    • Author(s)
      小野竜一
    • Organizer
      第93回日本遺伝学会学術年会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] リキッドバイオプシーによる毒性評価2021

    • Author(s)
      小野竜一
    • Organizer
      第48回日本毒性学会学術年会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] Liquid Biopsy for the Early Detection of Toxicity2021

    • Author(s)
      Ryuichi Ono
    • Organizer
      韓国毒性学会学術年会
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] EV-mediated horizontal gene transfer2020

    • Author(s)
      小野竜一
    • Organizer
      第43回日本分子生物学会学術年会
    • Related Report
      2020 Research-status Report
    • Invited
  • [Presentation] A novel risk for genome editing2020

    • Author(s)
      Ryuichi Ono
    • Organizer
      南米毒性学会学術年会
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Identification of novel EV-associated miRNAs as toxic biomarkers in mouse2020

    • Author(s)
      Ryuichi Ono
    • Organizer
      International Society for Extracellular Vesicles annual meeting 2020
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research
  • [Presentation] エクソソーム中のmiRNAをバイオマーカーとしたリキッドバイオプシー2020

    • Author(s)
      小野竜一
    • Organizer
      第47回日本毒性学会学術年会
    • Related Report
      2020 Research-status Report
  • [Presentation] Percellomeプロジェクトから見えてきたエピジェネティクス影響2019

    • Author(s)
      小野竜一、相崎健一、北嶋 聡、菅野 純
    • Organizer
      第45回日本毒性学会学術年会
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] Evaluation of exosomes as toxic biomarkers in mouse2019

    • Author(s)
      Ryuichi Ono, Yusuke Yoshioka, Yusuke Furukawa, Takahiro Ochiya, Satoshi Kitajima, Yoko Hirabayashi
    • Organizer
      15th International Congress of Toxicology (ICTXV)
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Molecular Basis of the 'Baseline Response' and 'Transient Response' Observed in the Newly Designed Repeated Dose Study: Epigenetic Modifications2019

    • Author(s)
      Ryuichi Ono, Satoshi Kitajima, Ken-ichi Aisaki, and Jun Kanno
    • Organizer
      Gordon Research Conference
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Exosome-mediated horizontal gene transfer: a possible new risk for genome editing2019

    • Author(s)
      Ryuichi Ono, Yukuto Yasuhiko, Kenichi Aisaki, Satoshi Kitajima, Jun Kanno, and Yoko Hirabayashi
    • Organizer
      55th Congress of the European Societies of Toxicology
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Exosome-mediated horizontal gene transfer: a possible new risk for genome editing2019

    • Author(s)
      Ryuichi Ono
    • Organizer
      第78回 日本癌学会学術総会
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] EV を介した遺伝子水平伝搬によるゲノム進化の可能性2019

    • Author(s)
      Ryuichi Ono
    • Organizer
      第6回日本細胞外小胞学会学術集会
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] Extracellular vesicles-mediated horizontal gene transfer: a possible new risk for genome editing2019

    • Author(s)
      Ryuichi Ono
    • Organizer
      第1回アジア環太平洋細胞外小胞学会学術集会
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] DSB Repair by Capture of Unintentional Sequences, an Emerging New Possible Risk for the Genome Editing2018

    • Author(s)
      Ryuichi Ono, Yukuto Yasuhiko, Ken-ichi Aisaki, Satoshi Kitajima, Jun Kanno, and Yoko Hirabayashi
    • Organizer
      ASAITOX
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Standardization of exosome isolation in mice corresponding to toxicity test2018

    • Author(s)
      Ryuichi Ono, Yusuke Yoshioka, Yusuke Furukawa, Satoshi Kitajima, Takahiro Ochiya, Yoko Hirabayashi
    • Organizer
      Japanese Society of Extracellular Vesicles Conference
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] A possible risk of genome editing for human gene therapy2018

    • Author(s)
      Ryuichi Ono, Keiko Tano, Satoshi Yasuda, Yukuto Yasuhiko, Kenichi Aisaki, Satoshi Kitajima, Jun Kanno, Yoji Sato and Yoko Hirabayashi
    • Organizer
      EUROTOX
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research

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Published: 2018-07-25   Modified: 2023-01-30  

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