Cas12a2 enzyme is programmed to identify specific RNA sequences rather than DNA. Upon successful recognition and binding to its target RNA, the protein undergoes a conformational change that unleashes indiscriminate collateral cleavage of intracellular DNA, effectively shredding the genetic material and inducing rapid cell death. In preclinical in vitro and in vivo models, a single administration of this targeted Cas12a2 system suppressed the proliferation of KRAS-mutated cancer cells by 50% and eliminated human papillomavirus (HPV)-infected cells with an efficacy exceeding 90%. Crucially, the intervention demonstrated high specificity, displaying no significant off-target cytotoxicity or damage to healthy tissue. This RNA-triggered DNA-shredding mechanism provides a highly adaptable and potent platform for oncology and virology, shifting the CRISPR paradigm from localized genetic correction to the targeted apoptosis of diseased cells, with future applications potentially expanding to target HIV and other robust infections.

Kadin Crosby, Ryan Jackson and colleagues report newly discovered details demonstrating how CRISPR Cas12a2 can be repurposed to discriminately kill cancer cells in the petri dish and in mice.