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Development of gene therapy for male infertility using transduction of artificial chromosome into germline stem cells

Research Project

Project/Area Number 18K14611
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 42040:Laboratory animal science-related
Research InstitutionOsaka University (2019)
Kyoto University (2018)

Principal Investigator

Watanabe Satoshi  大阪大学, 蛋白質研究所, 特任助教(常勤) (80769018)

Project Period (FY) 2018-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords遺伝子治療 / 人工染色体 / ベクター / 遺伝子導入 / 染色体導入 / GS細胞 / 生殖細胞 / 不妊症 / c-kit / 精子幹細胞 / 精巣 / 精子形成
Outline of Final Research Achievements

Germline stem cells are an attractive target for treatment of male infertility. However, this type of treatment has never been successful in the practical way because it is difficult to reproduce the physiological regution of expression of transgene. Here we tried to examine the feasibility of approaches using gene transduction into germline stem cells with arrificial chromosome to realize endogenous gene control. We successfully prepared an infertility model germline stem cells and a mouse artificial chromosome introduced with a target gene locus.

Academic Significance and Societal Importance of the Research Achievements

精子幹細胞は生殖細胞の中で唯一自己複製能力をもつ細胞であるため、発生工学の格好の標的である。ゲノム編集技術の登場により、近年ヒト生殖細胞での遺伝子操作について興味が高まっているが、現段階では適当な手法がない。申請者はこれまでプラスミドやウイルスベクターを用いて雄性不妊マウスの生殖細胞の遺伝子治療を試みたが、生理的な遺伝子発現を再現できず失敗してきた。人工染色体は生理的な遺伝子発現を再現しながら、ホスト細胞の遺伝子に改変を加えない。また、次世代に伝わらない点でも他の手法よりも優れており、ヒト生殖細胞研究および遺伝子治療法開発に大きな影響を与える。

Report

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

    (8 results)

All 2019 2018

All Journal Article (6 results) (of which Peer Reviewed: 6 results,  Open Access: 3 results) Presentation (1 results) (of which Int'l Joint Research: 1 results) Patent(Industrial Property Rights) (1 results) (of which Overseas: 1 results)

  • [Journal Article] ROS amplification drives mouse spermatogonial stem cell self-renewal.2019

    • Author(s)
      Morimoto H, Kanatsu-Shinohara M, Ogonuki N, Kamimura S, Ogura A, Yabe-Nishimura C, Mori Y, Morimoto T, Watanabe S, Otsu K, Yamamoto T, *Shinohara T.
    • Journal Title

      Life Sci Alliance

      Volume: 2 Issue: 2 Pages: 2-2

    • DOI

      10.26508/lsa.201900374

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] miR-124 dosage regulates prefrontal cortex function by dopaminergic modulation.2019

    • Author(s)
      Kozuka T, Omori Y, Watanabe S, Tarusawa E, Yamamoto H, Chaya T, Furuhashi M, Morita M, Sato T, Hirose S, Ohkawa Y, Yoshimura Y, Hikida T, Furukawa T.
    • Journal Title

      Sci Rep.

      Volume: Mar 5;9(1) Issue: 1 Pages: 3445-3445

    • DOI

      10.1038/s41598-019-38910-2

    • NAID

      120006579467

    • Related Report
      2019 Annual Research Report 2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Sendai virus-mediated transduction of mammalian spermatogonial stem cells.2019

    • Author(s)
      Watanabe S., Kanatsu-Shinohara, M., Shinohara T.
    • Journal Title

      Biol. Reprod.

      Volume: 100 Issue: 2 Pages: 523-534

    • DOI

      10.1093/biolre/ioy192

    • Related Report
      2019 Annual Research Report 2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] ROS amplification drives mouse spermatogonial stem cell self-renewal2019

    • Author(s)
      Hiroko Morimoto, Mito Kanatsu-Shinohara, Narumi Ogonuki, Satoshi Kamimura, Atsuo Ogura, Chihiro Yabe-Nishimura, Yoshifumi Mori, Takeshi Morimoto, Satoshi Watanbe, Kinya Otsu, and Takashi Shinohara
    • Journal Title

      Life Science Alliance

      Volume: in press

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Reversible inhibition of the blood-testis barrier protein improves stem cell homing in mouse testes2018

    • Author(s)
      Kanatsu-Shinohara M, Morimoto H, Watanabe S, Shinohara T.
    • Journal Title

      Journal of Reproduction and Development

      Volume: 64 Issue: 6 Pages: 511-522

    • DOI

      10.1262/jrd.2018-093

    • NAID

      130007530501

    • ISSN
      0916-8818, 1348-4400
    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Lrit1, a Retinal Transmembrane Protein, Regulates Selective Synapse Formation in Cone Photoreceptor Cells and Visual Acuity2018

    • Author(s)
      Ueno Akiko、Omori Yoshihiro、Sugita Yuko、Watanabe Satoshi、Chaya Taro、Kozuka Takashi、Kon Tetsuo、Yoshida Satoyo、Matsushita Kenji、Kuwahara Ryusuke、Kajimura Naoko、Okada Yasushi、Furukawa Takahisa
    • Journal Title

      Cell Reports

      Volume: 22 Issue: 13 Pages: 3548-3561

    • DOI

      10.1016/j.celrep.2018.03.007

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Gene transduction into spermatogonial stem cells and testes by Adeno-associated virus2018

    • Author(s)
      Satoshi Watanabe
    • Organizer
      Gordon Research conference, Mammalian Reproduction
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Patent(Industrial Property Rights)] 雄性生殖細胞またはセルトリ細胞にポリヌクレオチドを導入する方法2018

    • Inventor(s)
      渡邉哲史、篠原隆司
    • Industrial Property Rights Holder
      渡邉哲史、篠原隆司
    • Industrial Property Rights Type
      特許
    • Filing Date
      2018
    • Related Report
      2018 Research-status Report
    • Overseas

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Published: 2018-04-23   Modified: 2021-02-19  

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