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CoCas9 is a compact nuclease from the human microbiome for efficient and precise genome editing
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Journal Article
CoCas9 is a compact nuclease from the human microbiome for efficient and precise genome editing
2024
Overview
The expansion of the CRISPR-Cas toolbox is highly needed to accelerate the development of therapies for genetic diseases. Here, through the interrogation of a massively expanded repository of metagenome-assembled genomes, mostly from human microbiomes, we uncover a large variety (
n
= 17,173) of type II CRISPR-Cas loci. Among these we identify CoCas9, a strongly active and high-fidelity nuclease with reduced molecular size (1004 amino acids) isolated from an uncultivated
Collinsella
species. CoCas9 is efficiently co-delivered with its sgRNA through adeno associated viral (AAV) vectors, obtaining efficient in vivo editing in the mouse retina. With this study we uncover a collection of previously uncharacterized Cas9 nucleases, including CoCas9, which enriches the genome editing toolbox.
Cas9 nucleases hold clinical significance for genome editing therapies. Here the authors characterize CoCas9, a compact, efficient and precise Cas9 from the human microbiome, and show that delivery via AAV vectors enables efficient editing in the mouse retina, expanding the genome editing toolbox.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 45
/ 45/22
/ 45/44
/ Animals
/ CRISPR
/ CRISPR-Associated Protein 9 - genetics
/ CRISPR-Associated Protein 9 - metabolism
/ Editing
/ Genetic Vectors - metabolism
/ Genomes
/ Humanities and Social Sciences
/ Humans
/ Mice
/ Nuclease
/ Retina
/ RNA, Guide, CRISPR-Cas Systems
/ RNA, Guide, CRISPR-Cas Systems - genetics
/ RNA, Guide, CRISPR-Cas Systems - metabolism
/ Science
