CoCas9 is a compact nuclease from the human microbiome for efficient and precise genome editing.


Journal

Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555

Informations de publication

Date de publication:
24 Apr 2024
Historique:
received: 05 01 2024
accepted: 11 04 2024
medline: 25 4 2024
pubmed: 25 4 2024
entrez: 24 4 2024
Statut: epublish

Résumé

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.

Identifiants

pubmed: 38658578
doi: 10.1038/s41467-024-47800-9
pii: 10.1038/s41467-024-47800-9
doi:

Substances chimiques

CRISPR-Associated Protein 9 EC 3.1.-
RNA, Guide, CRISPR-Cas Systems 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

3478

Subventions

Organisme : EC | Horizon 2020 Framework Programme (EU Framework Programme for Research and Innovation H2020)
ID : 825825
Organisme : EC | Horizon 2020 Framework Programme (EU Framework Programme for Research and Innovation H2020)
ID : 101071041
Organisme : U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)
ID : 1U01CA230551
Organisme : EC | EU Framework Programme for Research and Innovation H2020 | H2020 Priority Excellent Science | H2020 European Research Council (H2020 Excellent Science - European Research Council)
ID : MetaPG-716575

Informations de copyright

© 2024. The Author(s).

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Auteurs

Eleonora Pedrazzoli (E)

Department of Computational, Cellular and Integrative Biology (CIBIO), University of Trento, 38123, Trento, Italy.

Michele Demozzi (M)

Department of Computational, Cellular and Integrative Biology (CIBIO), University of Trento, 38123, Trento, Italy.

Elisabetta Visentin (E)

Department of Computational, Cellular and Integrative Biology (CIBIO), University of Trento, 38123, Trento, Italy.

Matteo Ciciani (M)

Department of Computational, Cellular and Integrative Biology (CIBIO), University of Trento, 38123, Trento, Italy.

Ilaria Bonuzzi (I)

Department of Computational, Cellular and Integrative Biology (CIBIO), University of Trento, 38123, Trento, Italy.

Laura Pezzè (L)

Alia Therapeutics, Trento, Italy.

Lorenzo Lucchetta (L)

Department of Computational, Cellular and Integrative Biology (CIBIO), University of Trento, 38123, Trento, Italy.

Giulia Maule (G)

Department of Computational, Cellular and Integrative Biology (CIBIO), University of Trento, 38123, Trento, Italy.

Simone Amistadi (S)

Department of Computational, Cellular and Integrative Biology (CIBIO), University of Trento, 38123, Trento, Italy.
Université de Paris, Imagine Institute, Laboratory of chromatin and gene regulation during development, INSERM, UMR 1163, Paris, France.

Federica Esposito (F)

Telethon Institute of Genetics and Medicine (TIGEM), 80078, Pozzuoli (NA), Italy.

Mariangela Lupo (M)

Telethon Institute of Genetics and Medicine (TIGEM), 80078, Pozzuoli (NA), Italy.

Annarita Miccio (A)

Université de Paris, Imagine Institute, Laboratory of chromatin and gene regulation during development, INSERM, UMR 1163, Paris, France.

Alberto Auricchio (A)

Telethon Institute of Genetics and Medicine (TIGEM), 80078, Pozzuoli (NA), Italy.
Medical Genetics, Department of Advanced Biomedical Sciences, University of Naples "Federico II", 80131, Naples, Italy.

Antonio Casini (A)

Alia Therapeutics, Trento, Italy.

Nicola Segata (N)

Department of Computational, Cellular and Integrative Biology (CIBIO), University of Trento, 38123, Trento, Italy. nicola.segata@unitn.it.

Anna Cereseto (A)

Department of Computational, Cellular and Integrative Biology (CIBIO), University of Trento, 38123, Trento, Italy. anna.cereseto@unitn.it.

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