RNA-triggered Cas12a2 weaponizes DNA damage to kill targeted cells

A Nature study shows Cas12a2 can be activated by a specific RNA to trigger collateral double‑strand DNA breaks and cell death in both yeast and human cells, enabling programmable, transcription‑based elimination of cells that express a target transcript (e.g., HPV, KRAS mutations). The killing proceeds via extensive DNA damage and apoptosis with limited off‑target activation, and is demonstrated in vitro and in vivo, expanding the CRISPR toolbox for selective elimination of cells by transcriptional state.