Abstract:
:CRISPR-Cas9 technology would be enhanced by the ability to inhibit Cas9 function spatially, temporally, or conditionally. Previously, we discovered small proteins encoded by bacteriophages that inhibit the CRISPR-Cas systems of their host bacteria. These "anti-CRISPRs" were specific to type I CRISPR-Cas systems that do not employ the Cas9 protein. We posited that nature would also yield Cas9 inhibitors in response to the evolutionary arms race between bacteriophages and their hosts. Here, we report the discovery of three distinct families of anti-CRISPRs that specifically inhibit the CRISPR-Cas9 system of Neisseria meningitidis. We show that these proteins bind directly to N. meningitidis Cas9 (NmeCas9) and can be used as potent inhibitors of genome editing by this system in human cells. These anti-CRISPR proteins now enable "off-switches" for CRISPR-Cas9 activity and provide a genetically encodable means to inhibit CRISPR-Cas9 genome editing in eukaryotes. VIDEO ABSTRACT.
journal_name
Celljournal_title
Cellauthors
Pawluk A,Amrani N,Zhang Y,Garcia B,Hidalgo-Reyes Y,Lee J,Edraki A,Shah M,Sontheimer EJ,Maxwell KL,Davidson ARdoi
10.1016/j.cell.2016.11.017subject
Has Abstractpub_date
2016-12-15 00:00:00pages
1829-1838.e9issue
7eissn
0092-8674issn
1097-4172pii
S0092-8674(16)31589-6journal_volume
167pub_type
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