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Generation of antigen-specific T lymphocytes using genome editing technique

Research Project

Project/Area Number 17KK0189
Research Category

Fund for the Promotion of Joint International Research (Fostering Joint International Research)

Allocation TypeMulti-year Fund
Research Field Tumor therapeutics
Research InstitutionChiba University

Principal Investigator

Ouchi Yasuo  千葉大学, 大学院医学研究院, 特任助教 (70553858)

Project Period (FY) 2018 – 2021
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥15,600,000 (Direct Cost: ¥12,000,000、Indirect Cost: ¥3,600,000)
Keywordsゲノム編集技術 / 脂質ナノ粒子 / T細胞 / 免疫細胞療法 / COVID-19 / ゲノム編集 / がん免疫療法 / 免疫学 / バイオテクノロジー
Outline of Final Research Achievements

In this study, I developed non-viral genome editing tools that can be useful in the genome editing technology of T cells for successful cancer immunotherapy. As a result, we succeeded in developing mRNA lipid nanoparticles(LNPs) that enable highly efficient gene delivery into T cells, and developed genome-editing LNPs carrying CRISPR/Cas9 genome editing tools against PD-1 and TCR genes. Our genome-editing LNPs allows us to easily perform genome editing in human T cells. We have also developed LNPs carrying RNA editing tools against SARS-CoV-2 and confirmed that it showed high antiviral effects in the human lung organoid model of COVID-19.

Academic Significance and Societal Importance of the Research Achievements

近年、がん免疫細胞療法などを中心にゲノム編集技術の臨床応用が進められている。しかし、多くの問題を有しており、社会実装が困難な状況である。本研究ではT細胞を標的としたmRNA 脂質ナノ粒子を開発し、ゲノム編集技術を搭載することで簡便かつ迅速にゲノム編集T細胞を得る技術を開発した。また本技術を新型コロナウイルス感染症にも応用することで、高効率でSARS-CoV-2ウイルスを肺上皮細胞から除去できるRNA編集搭載脂質ナノ粒子を開発した。これらの研究成果は今後ゲノム編集技術を用いた治療法の社会実装を進めるうえで重要な基盤技術となると期待している。

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

    (11 results)

All 2022 2021 2020 2018

All Int'l Joint Research (1 results) Journal Article (8 results) (of which Int'l Joint Research: 6 results,  Peer Reviewed: 7 results,  Open Access: 6 results) Patent(Industrial Property Rights) (2 results)

  • [Int'l Joint Research] Salk institute for biological studies(米国)2018

    • Related Report
      2021 Annual Research Report
  • [Journal Article] FoxM1 delays senescence and extends lifespan2022

    • Author(s)
      Ouchi Y, Sahu S, Belmonte JCI
    • Journal Title

      Nature Aging

      Volume: -

    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Journal Article] Deletion of Tgfβ signal in activated microglia prolongs hypoxia-induced retinal neovascularization enhancing Igf1 expression and retinal leukostasis.2022

    • Author(s)
      Usui-Ouchi A, Eade K, Giles S, Ideguchi Y, Ouchi Y, Aguilar E, Guoqin W, Marra K, Berlow R, Friedlander M
    • Journal Title

      GLIA

      Volume: -

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Fibroblasts from different body parts exhibit distinct phenotypes in adult progeria Werner syndrome2021

    • Author(s)
      Kato H, Maezawa Y, Takayama N, Ouchi Y, Kaneko H, Kinoshita D, Takada-Watanabe A, Oshima M, Koshizaka M, Ogata H, Kubota Y, Mitsukawa N, Eto K, Iwama A, Yokote K.
    • Journal Title

      Aging (Albany NY)

      Volume: 13 Issue: 4 Pages: 4946-4961

    • DOI

      10.18632/aging.202696

    • Related Report
      2021 Annual Research Report 2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Generation of disease-specific and CRISPR/Cas9-mediated gene-corrected iPS cells from a patient with adult progeria Werner syndrome2021

    • Author(s)
      Kato Hisaya、Maezawa Yoshiro、Ouchi Yasuo、Takayama Naoya、Sone Masamitsu、Sone Kanako、Takada-Watanabe Aki、Tsujimura Kyoko、Koshizaka Masaya、Nagasawa Sayaka、Saitoh Hisako、Ohtaka Manami、Nakanishi Mahito、Tahara Hidetoshi、Shimamoto Akira、Iwama Atsushi、Eto Koji、Yokote Koutaro
    • Journal Title

      Stem Cell Research

      Volume: 53 Pages: 102360-102360

    • DOI

      10.1016/j.scr.2021.102360

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] SCD2-mediated monounsaturated fatty acid metabolism regulates cGAS-STING-dependent type I IFN responses in CD4+ T cells2021

    • Author(s)
      Kanno Toshio、Nakajima Takahiro、Yokoyama Satoru、Asou Hikari K.、Sasamoto Shigemi、Kamii Yasuhiro、Hayashizaki Koji、Ouchi Yasuo、Onodera Taishi、Takahashi Yoshimasa、Ikeda Kazutaka、Hasegawa Yoshinori、Kinjo Yuki、Ohara Osamu、Nakayama Toshinori、Endo Yusuke
    • Journal Title

      Communications Biology

      Volume: 4(1) Issue: 1 Pages: 820-820

    • DOI

      10.1038/s42003-021-02310-y

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Generation of mouse model of TGFBI-R124C corneal dystrophy using CRISPR/Cas9-mediated homology-directed repair2020

    • Author(s)
      Kitamoto Kohdai、Taketani Yukako、Fujii Wataru、Inamochi Aya、Toyono Tetsuya、Miyai Takashi、Yamagami Satoru、Kuroda Masahiko、Usui Tomohiko、Ouchi Yasuo
    • Journal Title

      Scientific Reports

      Volume: 10 Issue: 1 Pages: 2000-2000

    • DOI

      10.1038/s41598-020-58876-w

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] DUSP10 constrains innate IL-33-mediated cytokine production in ST2hi memory-type pathogenic Th2 cells2018

    • Author(s)
      Yamamoto, T., Endo, Y., Onodera, A., Hirahara, K., Asou, H., Nakajima, T., Kanno, T., Ouchi, Y., Uematsu, S., Nishimasu, H., Nureki, O., Tumes, D. J., Shimojo, N., and Nakayama, T.
    • Journal Title

      Nature Communications

      Volume: 9 Issue: 1 Pages: 4231-4231

    • DOI

      10.1038/s41467-018-06468-8

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Effects of long-term intake of a yogurt fermented with Lactobacillus delbrueckii subsp. bulgaricus 2038 and Streptococcus thermophilus 1131 on mice2018

    • Author(s)
      Usui Yuki、Kimura Yasumasa、Satoh Takeshi、Takemura Naoki、Ouchi Yasuo、Ohmiya Hiroko、Kobayashi Kyosuke、Suzuki Hiromi、Koyama Satomi、Hagiwara Satoko、Tanaka Hirotoshi、Imoto Seiya、Eberl G?rard、Asami Yukio、Fujimoto Kosuke、Uematsu Satoshi
    • Journal Title

      International Immunology

      Volume: 30 Issue: 7 Pages: 319-331

    • DOI

      10.1093/intimm/dxy035

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Patent(Industrial Property Rights)] 老化の評価方法2021

    • Inventor(s)
      大内靖夫、加藤尚也、横手幸太郎、江藤浩之、金子ひより、前澤善朗
    • Industrial Property Rights Holder
      大内靖夫、加藤尚也、横手幸太郎、江藤浩之、金子ひより、前澤善朗
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2021-097552
    • Filing Date
      2021
    • Related Report
      2021 Annual Research Report
  • [Patent(Industrial Property Rights)] アンチセンスオリゴマー2021

    • Inventor(s)
      大内靖夫、加藤尚也、横手幸太郎、江藤浩之
    • Industrial Property Rights Holder
      大内靖夫、加藤尚也、横手幸太郎、江藤浩之
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2021-081389
    • Filing Date
      2021
    • Related Report
      2021 Annual Research Report

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Published: 2018-01-25   Modified: 2025-03-27  

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