@article{Agudelo01012020, author = {Agudelo, Daniel and Carter, Sophie and Velimirovic, Minja and Duringer, Alexis and Rivest, Jean-François and Levesque, Sébastien and Loehr, Jeremy and Mouchiroud, Mathilde and Cyr, Denis and Waters, Paula J. and Laplante, Mathieu and Moineau, Sylvain and Goulet, Adeline and Doyon, Yannick}, title = {Versatile and robust genome editing with Streptococcus thermophilus CRISPR1-Cas9}, volume = {30}, number = {1}, pages = {107-117}, year = {2020}, doi = {10.1101/gr.255414.119}, abstract ={Targeting definite genomic locations using CRISPR-Cas systems requires a set of enzymes with unique protospacer adjacent motif (PAM) compatibilities. To expand this repertoire, we engineered nucleases, cytosine base editors, and adenine base editors from the archetypal Streptococcus thermophilus CRISPR1-Cas9 (St1Cas9) system. We found that St1Cas9 strain variants enable targeting to five distinct A-rich PAMs and provide a structural basis for their specificities. The small size of this ortholog enables expression of the holoenzyme from a single adeno-associated viral vector for in vivo editing applications. Delivery of St1Cas9 to the neonatal liver efficiently rewired metabolic pathways, leading to phenotypic rescue in a mouse model of hereditary tyrosinemia. These robust enzymes expand and complement current editing platforms available for tailoring mammalian genomes.}, URL = {http://genome.cshlp.org/content/30/1/107.abstract}, eprint = {http://genome.cshlp.org/content/30/1/107.full.pdf+html}, journal = {Genome Research} }