| Title: |
Versatile and robust genome editing with Streptococcus thermophilus CRISPR1-Cas9 |
| Authors: |
Agudelo, Daniel; Carter, Sophie; Velimirovic, Minja; Duringer, Alexis; Rivest, Jean-François; Levesque, Sébastien; Loehr, Jérémy; Mouchiroud, Mathilde; Cyr, Denis; Waters, Paula; Laplante, Mathieu; Moineau, Sylvain; Goulet, Adeline; Doyon, Yannick |
| Contributors: |
Centre de recherche du CHU de Québec-Université Laval (CRCHUQ); CHU de Québec–Université Laval; Université Laval Québec (ULaval)-Université Laval Québec (ULaval); Université Laval Québec (ULaval); CHUS – Centre Hospitalier Universitaire de Sherbrooke Sherbrooke, QC, Canada; Université Laval, centre de recherche sur le cancer, Québec, Canada; Département de Biochimie, Microbiologie et Bioinformatique Québec, Canada; Université Laval Québec (ULaval)-Pavillon Charles-Eugène-Marchand Québec, Canada (CHM); Groupe de Recherche en Écologie Buccale (GREB) and Félix d’Hérelle Reference Center for Bacterial Viruses, Faculté de Médecine Dentaire; Architecture et fonction des macromolécules biologiques (AFMB); Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE); Centre National de la Recherche Scientifique (CNRS); Aix Marseille Université (AMU); Laboratoire d'ingénierie des systèmes macromoléculaires (LISM); Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS); ANR-18-CE11-0016,PHARE,Vengeance de phages: analyses structurales et fonctionnelles de protéines anti CRISPR-Cas9(2018) |
| Source: |
ISSN: 1088-9051. |
| Publisher Information: |
CCSD; Cold Spring Harbor Laboratory Press |
| Publication Year: |
2020 |
| Collection: |
Aix-Marseille Université: HAL |
| Subject Terms: |
[SDV]Life Sciences [q-bio] |
| Description: |
International audience ; 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. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| Relation: |
WOS: 000506573000010 |
| DOI: |
10.1101/gr.255414.119 |
| Availability: |
https://hal.science/hal-03050601; https://hal.science/hal-03050601v1/document; https://hal.science/hal-03050601v1/file/Genome%20Res.-2020-Agudelo-107-17.pdf; https://doi.org/10.1101/gr.255414.119 |
| Rights: |
https://creativecommons.org/licenses/by-nc/4.0/ ; info:eu-repo/semantics/OpenAccess |
| Accession Number: |
edsbas.A399F1C8 |
| Database: |
BASE |