Previously, in 2022, the team introduced a CRISPR-based approach that required delivering more than 20 guide RNAs simultaneously to induce multiple double-strand breaks (DSBs) in cancer DNA, effectively killing the cells. However, this method faced challenges related to delivery complexity and the risk of damaging normal tissues.

The newly developed technique requires only four guide RNAs and exploits the synergy between CRISPR and PARP inhibitors—drugs that block a critical DNA repair protein. By inducing single-strand breaks (SSBs) instead of DSBs and preventing their repair, this approach effectively triggers cancer cell death with fewer guide RNAs, minimizing off-target effects and enhancing safety.

PARP inhibitors are well-established targeted therapies, primarily used for ovarian and breast cancers with BRCA mutations. This combined strategy broadens their application to other cancer types lacking such genetic alterations.