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2023 Fiscal Year Annual Research Report

新規CRISPR-Cas系酵素の構造解析および作動機構の解明

Research Project

Project/Area Number 22KJ0608
Allocation TypeMulti-year Fund
Research InstitutionThe University of Tokyo

Principal Investigator

中川 綾哉  東京大学, 理学系研究科, 特別研究員(DC1)

Project Period (FY) 2023-03-08 – 2024-03-31
KeywordsCRISPR-Cas
Outline of Annual Research Achievements

CRISPR-Cas systems in prokaryotes provide adaptive immunity against foreign nucleic acids, and are divided into two classes (classes 1 and 2) and six types (type I-VI). In the class 1 systems, multiple Cas proteins associate with a guide RNA to de-grade invading nucleic acids. By contrast, in the class 2 systems, single multidomain Cas proteins, Cas9 (type II), Cas12 (type V), and Cas13 (type VI), associate with their guide RNA to form effector complexes responsible for target nucleic acid cleavage. Since class 2 Cas proteins operate as single components, they have been harnessed for various innovative techniques, such as genome editing. I performed biochemical and structural analyses on three effectors associated with the class 2 CRISPR-Cas system: Cas9 (type II), Cas12 (type V), and Cas13 (type VI), elu-cidating the mechanistic details of the RNA-guided DNA/RNA cleavage. These find-ings advance our understanding of the conservation and divergence among the class 2 CRISPR-Cas systems, and shed light on their evolutionary scenario originating from transposon-encoded proteins. Furthermore, I rationally engineered com-pact Cas ef-fectors with enhanced activities. These results expand the CRISPR-Cas toolbox for therapeutic genome engineering.

  • Research Products

    (2 results)

All 2023

All Journal Article (2 results)

  • [Journal Article] Cryo-EM structure of the transposon-associated TnpB enzyme.2023

    • Author(s)
      Ryoya Nakagawa, Hisato Hirano, Satoshi N. Omura, Feng Zhang & Osamu Nureki
    • Journal Title

      Nature

      Volume: 616 Pages: 390-397

    • DOI

      10.1038/s41586-023-05933-9

  • [Journal Article] An AsCas12f-based compact genome-editing tool derived by deep mutational scanning and struc-tural analysis.2023

    • Author(s)
      Tomohiro Hino, Satoshi N. Omura, Ryoya Nakagawa, Osamu Nureki
    • Journal Title

      Cell

      Volume: 186 Pages: 4920-4935

    • DOI

      10.1016/j.cell.2023.08.031

URL: 

Published: 2024-12-25  

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