The AcrIIA4 protein (red) could improve the CRISPR-Cas9 editing system by stopping it cutting DNA (purple) in the wrong places.

The AcrIIA4 protein (red) could improve the CRISPR-Cas9 editing system by stopping it cutting DNA (purple) in the wrong places.  Credit: Fuguo Jiang/UC Berkeley

Molecular biology

An ‘anti-CRISPR’ tool cleans up gene edits

Adding protein to human cells makes CRISPR–Cas9 more specific.

A natural inhibitor of the CRISPR–Cas9 gene-editing system could be harnessed to reduce editing errors. 

CRISPR–Cas9 is a microbial immune system that has been harnessed as a tool for making precise, targeted changes to genomes, but it sometimes cuts DNA at off-target sites. Jacob Corn and Jennifer Doudna of the University of California, Berkeley, and their colleagues studied a protein called AcrIIA4, which some viruses use to inhibit this system in nature. 

They found that the protein can bind to the Cas9 enzyme and interfere with its ability to target DNA for cutting. Adding AcrIIA4 to human cells before genome editing inhibits the process. But adding it afterwards only partially inhibits editing at targeted sites, and reduces the number of off-target Cas9 cuts.