Potent CRISPR-Cas9 inhibitors fromStaphylococcusgenomes
Abstract
Many mobile genetic elements contain anti-CRISPRs (Acrs) to evade host CRISPR defenses. Acrs have been discovered that inhibit therapeutically relevant CRISPR-Cas gene editors such as Cas12 and Cas9, including many inhibitors forStreptococcus pyogenesCas9 (SpyCas9). However, there are few inhibitors known for the Cas9 fromStaphylococcus aureus(SauCas9), which is both highly active in human cells and easier to deliver than SpyCas9 due to its smaller size. In this work, we search withinStaphylococcusgenomes for Acrs able to inhibit SauCas9. We discover three Acrs (AcrIIA13, AcrIIA14, and AcrIIA15) and demonstrate all three are able to inhibit CRISPR-Cas9 gene editing. Our findings highlight the utility of our Acr search method for finding Acrs against specific Cas nucleases.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Mar 10, 2020
- Source ID
- 10.1073/pnas.1917668117
Entities
People
- Blake Mcmahon
- Christof Fellmann
- Haridha Shivram
- Jennifer Doudna
- Kyle E Watters
- Rachel J. Lew
Organizations
- Howard Hughes Medical Institute
- Innovative Genomics Institute
- National Institute of General Medical Sciences
- Paul G. Allen Family Foundation
- University of California
- University of California, San Francisco
- Yusuf Hamied Department of Chemistry