Naturally Occurring Off-Switches for CRISPR-Cas9.
Cell
; 167(7): 1829-1838.e9, 2016 Dec 15.
Article
em En
| MEDLINE
| ID: mdl-27984730
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.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Sistemas CRISPR-Cas
/
Edição de Genes
/
Neisseria meningitidis
Limite:
Humans
Idioma:
En
Revista:
Cell
Ano de publicação:
2016
Tipo de documento:
Article
País de afiliação:
Canadá