| Project/Area Number |
16K18400
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Laboratory animal science
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| Research Institution | Kyoto University |
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Principal Investigator |
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| Research Collaborator |
Shinohara Takashi 京都大学, 大学院医学系研究科遺伝医学講座分子遺伝学分野, 教授
Ogura Atsuo 理化学研究所バイオリソースセンター, 遺伝工学基盤技術室, 室長
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| Project Period (FY) |
2016-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2016: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | 精巣 / 精子幹細胞 / GS細胞 / アデノ随伴ウイルス / 遺伝子治療 / 不妊症 / 遺伝子改変 / 遺伝子導入 / 生殖細胞 / GS cells / 精子形成 |
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| Outline of Final Research Achievements |
Adeno-associated virus (AAV) penetrates the blood-brain barrier but it is unknown whether AAV penetrates other tight junction. Genetic manipulation of testis has been hampered by the basement membrane of seminiferous tubules and the blood-testis barrier (BTB) Here we demonstrate in vivo genetic manipulation of spermatogonial stem cells (SSCs) and their microenvironemnt via AAV1/9. AAV1/9 microinjected into the seminiferous tubules penetrated both the basement membrane and BTB, thereby transducing not only Sertoli and SSCs but also peritubular cells and Leydig cells. Moreover, when congenitally infertile KitlSl/KitlSl-d mouse testes with defective Sertoli cells received Kitl-expressing AAVs, spermatogenesis regenerated and offspring were produced. Thus AAV1/9 allows efficient germline and niche manipulation by penetrating the BTB and basement membrane, providing a promising strategy for the development of gene therapies for reproductive defects.
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