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Systematic discovery of natural CRISPR-Cas12a inhibitors.

  • Author(s): Watters, Kyle E
  • Fellmann, Christof
  • Bai, Hua B
  • Ren, Shawn M
  • Doudna, Jennifer A
  • et al.

Published Web Location

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6185749/
No data is associated with this publication.
Abstract

Cas12a (Cpf1) is a CRISPR-associated nuclease with broad utility for synthetic genome engineering, agricultural genomics, and biomedical applications. Although bacteria harboring CRISPR-Cas9 or CRISPR-Cas3 adaptive immune systems sometimes acquire mobile genetic elements encoding anti-CRISPR proteins that inhibit Cas9, Cas3, or the DNA-binding Cascade complex, no such inhibitors have been found for CRISPR-Cas12a. Here we use a comprehensive bioinformatic and experimental screening approach to identify three different inhibitors that block or diminish CRISPR-Cas12a-mediated genome editing in human cells. We also find a widespread connection between CRISPR self-targeting and inhibitor prevalence in prokaryotic genomes, suggesting a straightforward path to the discovery of many more anti-CRISPRs from the microbial world.

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