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Science. 2018 Oct 12;362(6411):240-242. doi: 10.1126/science.aau5174. Epub 2018 Sep 6.

Discovery of widespread type I and type V CRISPR-Cas inhibitors.

Author information

1
Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94143, USA.
2
Molecular Pathology Unit, Massachusetts General Hospital, Charlestown, MA 02129, USA.
3
Center for Cancer Research, Massachusetts General Hospital, Charlestown, MA 02129, USA.
4
Center for Computational and Integrative Biology, Massachusetts General Hospital, Charlestown, MA 02129, USA.
5
Department of Pathology, Harvard Medical School, Boston, MA 02115, USA.
6
Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94143, USA. joseph.bondy-denomy@ucsf.edu.
7
Quantitative Biosciences Institute, University of California, San Francisco, San Francisco, CA 94143, USA.

Abstract

Bacterial CRISPR-Cas systems protect their host from bacteriophages and other mobile genetic elements. Mobile elements, in turn, encode various anti-CRISPR (Acr) proteins to inhibit the immune function of CRISPR-Cas. To date, Acr proteins have been discovered for type I (subtypes I-D, I-E, and I-F) and type II (II-A and II-C) but not other CRISPR systems. Here, we report the discovery of 12 acr genes, including inhibitors of type V-A and I-C CRISPR systems. AcrVA1 inhibits a broad spectrum of Cas12a (Cpf1) orthologs-including MbCas12a, Mb3Cas12a, AsCas12a, and LbCas12a-when assayed in human cells. The acr genes reported here provide useful biotechnological tools and mark the discovery of acr loci in many bacteria and phages.

Comment in

PMID:
30190308
PMCID:
PMC6520112
DOI:
10.1126/science.aau5174
[Indexed for MEDLINE]
Free PMC Article

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