January 22, 2024

Ph.D. student Mason Myers of the Zhang lab is a lead author of a research article in Molecular Cell

Exploiting activation and inactivation mechanisms in type I-C CRISPR-Cas3 for genome-editing applications

In research published in Molecular Cell, a team from the Zhang lab describes their development of the first off-switches for Type I CRISPR (aka CRISPR-Cas3) eukaryotic genome engineering. Using genetic, biochemical and human cell culture approaches, they characterized two phage-encoded small protein inhibitors of CRISPR-Cas3, the anti-CRISPRs AcrIC8 and AcrIC9, and successfully harnessed them into robust "off-switches" that can turn off Type I CRISPR-mediated gene targeting or gene activation in human cells. Their results pave the way toward safer human genome engineering by using an anti-CRISPR strategy to reduce unwanted off-target effects. In collaboration with the Ke lab from Cornell University, the team also reports cryo-EM snapshots that reveal the mechanisms of CRISPR-Cas3 operation and its inhibition by anti-CRISPRs at high resolution.

Research article in Molecular Cell

"CRISPR off-switches: A path towards safer genome engineering?" by Kelly Malcom, Michigan Medicine