Résumé : CRISPR-Cas systems have emerged as a powerful technology for precision genome editing in cells and organisms. The CRISPR-associated protein Cas9 is an RNA-guided DNA nuclease that associates with an unusual dual-RNA guide structure and cleaves double-stranded DNA sequences complementary to a 20-nucleotide sequence in the guide RNA. The enzyme can be programmed using single-molecule guide RNAs to induce double-strand DNA breaks in genomic DNA, paving the way for RNA-guided genetic genome editing. Our previous work revealed crystal structures of Cas9 and its complexes with a guide RNA and a DNA target. The structures shed light on the molecular mechanism of Cas9-mediated DNA binding and cleavage and reveal the conformational transitions occurring during the process. Our current studies focus on exploring the mechanism of Cas9 in greater detail and on understanding complementary genome editing tools such as Cpf1/Cas12a. These studies provide the structural framework for the ongoing development of CRISPR-Cas for a new generation of genome editing tools and technologies.
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