Establishment of universal iPS cells for regenerative medicine applications through regulated HLA expression
| Project/Area Number |
17K07256
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | 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 | Kyoto University |
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Principal Investigator |
Woltjen Knut 京都大学, iPS細胞研究所, 准教授 (50589489)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | Human leukocyte antigen / HLA / ゲノム編集 / iPS細胞 / CRISPR Cas9 / KRAB / B2M / allograft / alloresponse / 再生医療 / ゲノム生物工学 / 個別化医療 |
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| Outline of Final Research Achievements |
Human leukocyte antigens (HLA) are highly polymorphic gene loci that encode cell-surface glycoproteins which are the strongest transplant antigens leading to T-cell activation, antibody production, and allograft rejection. Personalized iPS cells hold great promise as cellular therapies by autologous transplantation. However, on-demand generation or banking of individualized iPS cells to treat all patients is neither technically nor economically feasible. On the other hand, ‘Universal’ iPS cells which bear no intrinsic HLA signature, would avoid immune rejection. We developed an epigenetic regulation system to control HLA gene expression and presentation. We explored the reversibility of the system with the goal of providing widely applicable and safe iPS cells for regenerative medicine.
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| Academic Significance and Societal Importance of the Research Achievements |
We created a reversible gene regulation system which is sensitive and could be applied in vivo. We made a new finding that epigenetic changes caused by an RNA-programmable repressor may persist through differentiation. Our system should be useful for the study of gene function and immunoregulation.
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Report
(4 results)
Research Products
(14 results)
