Researchers reported an engineered, compact nuclease-dead Cas12m variant for multiplexed gene activation in vivo using a single AAV vector design. The platform (smCRISPRa) leverages Cas12m’s self-processing of precursor crRNA to enable an all-in-one multi-gRNA array, addressing AAV payload constraints that often limit multiplex strategies. Preclinical testing in mouse models of Duchenne muscular dystrophy and Scn1a haploinsufficiency reported phenotypic rescue. The results strengthen the technical case for compact multiplexing tools in gene-regulation therapies, though translation will depend on durability, tissue targeting, and safety of multiplex gene activation.