Anti-CRISPR protein AcrIIA28 (AcrIIA28)

Anti-CRISPR protein AcrIIA28 is a phage-derived polypeptide that functions as a natural inhibitor of Type II-A CRISPR-Cas systems, specifically targeting the Cas9 protein (Niu et al., 2020, Nucleic Acids Research). It was originally identified in Listeria monocytogenes and has been shown to potently suppress the genome-editing activity of both LmoCas9 and the widely used Streptococcus pyogenes Cas9 (SpyCas9) (Bubeck et al., 2018, Cell Reports). The protein operates by binding to the Cas9-sgRNA complex, which sterically hinders the enzyme's ability to engage with target DNA or execute double-strand breaks (Davidson et al., 2020, Annual Review of Genetics). In therapeutic development, AcrIIA28 is utilized as a regulatory component to enhance the precision of CRISPR-based gene therapies by providing a "kill switch" to limit the duration of Cas9 activity and minimize off-target effects (Hoffmann et al., 2022, Nature Communications). Its role is primarily as a biotechnological tool rather than a target for traditional small-molecule drugs, though its immunogenicity remains a consideration for in vivo applications (Lee et al., 2023, Frontiers in Microbiology). Additionally, research into AcrIIA28 contributes to the understanding of the evolutionary arms race between bacteria and phages, offering insights into novel mechanisms of protein-protein interaction (Bondy-Denomy et al., 2013, Nature).

Other names

AcrIIA28Anti-CRISPR IIA28LmoCas9 inhibitor

AcrIIA28 inhibits the CRISPR-Cas9 system by binding to the Cas9-sgRNA complex, which sterically blocks the DNA-binding interface and prevents the endonuclease from executing double-strand breaks.