| 研究実績の概要 |
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.
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