A new protein that is able to inhibit the Cas9 protein from Streptococcus iniae (SinCas9). SinCas9 is capable of robust DNA cleavage and offers an immune orthogonal Cas9 for use in gene editing in human cells. The inhibitor is a small protein from a phage and is capable of inhibiting SinCas9 activity in vitro and in human cell genome editing experiments.
The newly discovered protein inhibitor could be used to prevent, limit, etc. gene editing from SinCas9. This may be relevant for biodefense use, limiting off-target editing, or other applications where reduced activity or rapid inhibition is desired.