| Project/Area Number |
17K19617
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| Research Category |
Grant-in-Aid for Challenging Research (Exploratory)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Tumor biology and related fields
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| Research Institution | University of Occupational and Environmental Health, Japan |
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Principal Investigator |
DOI Tomomitsu 産業医科大学, 医学部, 講師 (70437218)
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| Co-Investigator(Kenkyū-buntansha) |
岩井 佳子 日本医科大学, 大学院医学研究科, 大学院教授 (90362467)
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| Project Period (FY) |
2017-06-30 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
Fiscal Year 2019: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | 免疫チェックポイント / CRISPR/Cas9 / ゲノムワイドスクリーニング / 腫瘍免疫 / 免疫学 |
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| Outline of Final Research Achievements |
In this study, we conducted a comprehensive screening for tumor immune escape genes in mice using a genome-wide CRISPR / Cas9 knockout library. Many of the obtained candidate genes could not reproduce the enrichment effect seen in the library in knockout cells individually prepared for validation. The competition between clones in the tumor and the variation within the clone that did not depend on gene knockout were assumed to be the cause, and it could be the task(s) to be solved for future library screening in vivo.
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| Academic Significance and Societal Importance of the Research Achievements |
CRISPR/Cas9によるゲノム編集技術の登場により、全遺伝子を標的として、破壊による機能解析が可能となった。しかし、多くのスクリーニングは試験管内で行われていて、生体内における機能を必ずしも反映していない。本研究では、腫瘍の免疫回避機構をマウス個体内で行った。結果的に、ノックアウト遺伝子が効率よく濃縮されなかったが、今後、生体内でライブラリースクリーニングを行う際の課題を提示できた。
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