| Project/Area Number |
26290066
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Partial Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Medical genome science
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| Research Institution | Tokai University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
佐藤 健人 東海大学, 医学部, 准教授 (50235363)
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| Research Collaborator |
SHIINA Takashi 東海大学, 医学部, 准教授 (00317744)
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| Project Period (FY) |
2014-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| Budget Amount *help |
¥16,900,000 (Direct Cost: ¥13,000,000、Indirect Cost: ¥3,900,000)
Fiscal Year 2016: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2015: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2014: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000)
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| Keywords | iPS細胞 / 移植片拒絶回避 / HLA遺伝子 / 遺伝子欠失 / CRISPR/Cas9 / 遺伝子発現制御 / NK細胞 / HLA発現低下 / ベータ２m遺伝子 / 移植片拒絶 / HLA / CRISPR / 遺伝子発現 / 再生 / 遺伝子工学 / HLA抗原 / 発現抑制 / 遺伝子変異 / 遺伝子改変 / MHC / 主要組織適合抗原 / 多分化能 |
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| Outline of Final Research Achievements |
When stocked iPSCs are utilized to allograft transplantation, immune responses to transplanted cells should be controlled. Since construction of stocked iPSCs covering all HLA allo-types are beyond the realm of possibility, various approaches to overcome the difficulty are to be explored. While we easily manipulated HLA gene locus by CRISPR/Cas9 system, it was suggested that some selection cassettes harboring PB sequences is useful to select genome-edited cells. It was raised the possibility that beta;2m-deificient iPSCs would be the target of NK cells. Therefore, instead of all HLA class I, deletion of single HLA gene locus, such as HLA-A, would be effective to apply stocked iPSCs to patients who share the HLA allo-type other than the deleted HLA-A gene locus. It is also important to establish the in vivo experimental system in which human immune cells are re-constructed and the reactions to iPSC-derived allo antigens are validated.
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