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PMID:27984730
| Citation |
Pawluk, A, Amrani, N, Zhang, Y, Garcia, B, Hidalgo-Reyes, Y, Lee, J, Edraki, A, Shah, M, Sontheimer, EJ, Maxwell, KL and Davidson, AR (2016) Naturally Occurring Off-Switches for CRISPR-Cas9. Cell 167:1829-1838.e9 |
|---|---|
| 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. |
| Links |
PubMed PMC5757841 Online version:10.1016/j.cell.2016.11.017 |
| Keywords |
Bacterial Proteins/genetics; Bacterial Proteins/metabolism; CRISPR-Cas Systems; Cell Line; Gene Editing; Humans; Neisseria meningitidis/genetics; Neisseria meningitidis/metabolism |
Significance
Annotations
| Gene product | Qualifier | GO Term | Evidence Code | with/from | Aspect | Extension | Notes | Status |
|---|---|---|---|---|---|---|---|---|
| GO:0110133: negative regulation of CRISPR-cas system |
ECO:0005027: |
P |
Figure 1 (C) shows that acrIIC3 inhibits CRISPR interference in N. meningitidis using the transformation assay of N. meningitidis acrIIC3Nme |
complete | ||||
Notes
See also
References
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