An experimental census of retrons for DNA production and genome editing.
Journal
Nature biotechnology
ISSN: 1546-1696
Titre abrégé: Nat Biotechnol
Pays: United States
ID NLM: 9604648
Informations de publication
Date de publication:
17 Sep 2024
17 Sep 2024
Historique:
received:
21
12
2023
accepted:
12
08
2024
medline:
18
9
2024
pubmed:
18
9
2024
entrez:
17
9
2024
Statut:
aheadofprint
Résumé
Retrons are bacterial immune systems that use reverse-transcribed DNA (RT-DNA) to detect phage infection. They are also deployed for genome editing, where they are modified so that the RT-DNA encodes an editing donor. Retrons are common in bacterial genomes, and thousands of unique retrons have been predicted bioinformatically. However, few have been characterized experimentally. We add to the corpus of experimentally studied retrons, finding 62 empirically determined, natural RT-DNAs that are not predictable from the retron sequence alone. We synthesize >100 previously untested retrons to identify the natural sequence of RT-DNA they produce, quantify their RT-DNA production and test the relative efficacy of editing using retron-derived donors to edit bacterial, phage and human genomes. We observe large diversity in RT-DNA production and editing rates across retrons, finding that top-performing editors are drawn from a subset of the retron phylogeny and outperform those used in previous studies, reaching precise editing rates of up to 40% in human cells.
Identifiants
pubmed: 39289529
doi: 10.1038/s41587-024-02384-z
pii: 10.1038/s41587-024-02384-z
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : National Science Foundation (NSF)
ID : MCB 2137692
Organisme : U.S. Department of Health & Human Services | NIH | National Institute of Biomedical Imaging and Bioengineering (NIBIB)
ID : R21EB031393
Organisme : U.S. Department of Health & Human Services | NIH | National Institute of Biomedical Imaging and Bioengineering (NIBIB)
ID : 1DP2GM140917
Informations de copyright
© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.
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