Systematic discovery of natural CRISPR-Cas12a inhibitors

Author:

Watters Kyle E.1ORCID,Fellmann Christof12ORCID,Bai Hua B.1,Ren Shawn M.1,Doudna Jennifer A.12345ORCID

Affiliation:

1. Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA.

2. Gladstone Institutes, San Francisco, CA 94158, USA.

3. Department of Chemistry, University of California, Berkeley, Berkeley, CA 94720, USA.

4. Innovative Genomics Institute, University of California, Berkeley, Berkeley, CA 94720, USA.

5. Howard Hughes Medical Institute, University of California, Berkeley, Berkeley, CA 94720, USA.

Abstract

Cas12 inhibitors join the anti-CRISPR family Bacteria and their phages continually coevolve in a molecular arms race. For example, phages use anti-CRISPR proteins to inhibit the bacterial type I and II CRISPR systems (see the Perspective by Koonin and Makarova). Watters et al. and Marino et al. used bioinformatic and experimental approaches to identify inhibitors of type V CRISPR-Cas12a. Cas12a has been successfully engineered for gene editing and nucleic acid detection. Some of the anti-Cas12a proteins identified in these studies had broad-spectrum inhibitory effects on Cas12a orthologs and could block Cas12a-mediated genome editing in human cells. Science , this issue p. 236 , p. 240 ; see also p. 156

Funder

Howard Hughes Medical Institute

National Institute of General Medical Sciences

Paul G. Allen Family Foundation

Defense Sciences Office, DARPA

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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