{"doi":"10.1101/gr.255414.119","title":"Versatile and robust genome editing with <i>Streptococcus thermophilus</i> CRISPR1-Cas9","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.","journal":"Genome Research","year":2020,"id":118431,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":81,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9574,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":550627,"name":"Sophie Carter","orcid":"0000-0002-9817-0029","position":1,"is_corresponding":false},{"id":550628,"name":"Minja Velimirovic","orcid":"0000-0001-5221-6194","position":2,"is_corresponding":false},{"id":550629,"name":"Alexis Duringer","orcid":"0000-0001-5174-5369","position":3,"is_corresponding":false},{"id":550630,"name":"Jean-François Rivest","orcid":"0000-0002-8865-8063","position":4,"is_corresponding":false},{"id":550631,"name":"Sébastien Levesque","orcid":"0000-0002-1671-1929","position":5,"is_corresponding":false},{"id":550632,"name":"Jérémy Loehr","orcid":"0000-0002-9746-800X","position":6,"is_corresponding":false},{"id":550633,"name":"Mathilde Mouchiroud","orcid":"0000-0002-8879-0988","position":7,"is_corresponding":false},{"id":550634,"name":"Denis Cyr","orcid":"0000-0003-1914-6475","position":8,"is_corresponding":false},{"id":550635,"name":"Paula J. Waters","orcid":"0000-0003-4898-1859","position":9,"is_corresponding":false},{"id":550636,"name":"Mathieu Laplante","orcid":"0000-0002-1752-6741","position":10,"is_corresponding":false},{"id":550637,"name":"Sylvain Moineau","orcid":"0000-0002-2832-5101","position":11,"is_corresponding":false},{"id":550638,"name":"Adeline Goulet","orcid":"0000-0002-5971-9488","position":12,"is_corresponding":false},{"id":550639,"name":"Yannick Doyon","orcid":"0000-0002-3889-9563","position":13,"is_corresponding":false},{"id":550626,"name":"Daniel Agudelo","orcid":"0000-0002-8794-4279","position":0,"is_corresponding":true}],"reference_count":84,"raw_metadata":null,"created_at":"2026-07-18T23:13:58.531532Z","pmid":"31900288","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}