| Project/Area Number |
18K19284
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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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| Review Section |
Medium-sized Section 43:Biology at molecular to cellular levels, and related fields
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| Research Institution | The University of Tokyo |
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Principal Investigator |
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| Project Period (FY) |
2018-06-29 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
Fiscal Year 2019: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
Fiscal Year 2018: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
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| Keywords | CRISPR / CRISPR-Cas9 |
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| Outline of Final Research Achievements |
Cas9 is an RNA-guided DNA nuclease derived from prokaryotic CRISPR-Cas adaptive immune systems, and associates with a guide RNA to cleave double-stranded DNA targets. Therefore, Cas9 is widely used as a powerful genome-editing tool. In this study, we determined the 3D structures of Cas9 and Cas12f, which provide mechanistic insights into their RNA-guide DNA cleavage. Based on the structural information, we further engineered Cas9 variants with improved functionality, thereby extending the utility of CRISPR-based genome engineering technologies.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究では、小型Cas9の結晶構造および小型Cas12fのクライオ電子顕微鏡構造を決定した。これらの立体構造から、CRISPR-Cas酵素の多様なRNA認識機構、DNA認識機構、DNA切断機構が原子レベルで明らかになった。さらに、得られた構造情報を利用し、標的範囲の拡張したCas9改変体の開発にも成功した。これらの成果は、ゲノム編集技術の高度化に貢献するものである。
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