The U.S. Food and Drug Administration’s recent approval of the first CRISPR-Cas9–based gene therapy has marked a major milestone in biomedicine, validating genome editing as a promising treatment strategy for disorders like sickle cell disease, muscular dystrophy, and certain cancers.

CRISPR-Cas9, often likened to “molecular scissors,” allows scientists to cut DNA at targeted sites to snip, repair, or replace genes. But despite its power, Cas9 poses a critical safety risk: The active enzyme can linger in cells and cause unintended DNA breaks — so-called off-target effects — which may trigger harmful mutations in healthy genes.

Now, researchers in the labs of Ronald T. Raines, MIT professor of chemistry, and Amit Choudhary, professor of medicine at Harvard Medical School, have engineered a precise way to turn Cas9 off after its job is done — significantly reducing off-target effects and improving the clinical safety of gene editing. Their findings are detailed in a new paper published in the Proceedings of the National Academy of Sciences (PNAS).