Researchers published an engineered, compact denCas12m-based CRISPR activation system (smCRISPRa) that supports multiplexed gene activation in vivo from a single AAV vector. The platform addresses AAV payload limits by using Cas12m’s self-processing properties to generate multiple functional guides from a multi-gRNA array inside cells. In mouse models of Duchenne muscular dystrophy and Scn1a haploinsufficiency, the study reported phenotypic rescue and demonstrated higher-order multiplexing. Because conventional CRISPRa designs often exceed AAV capacity, the work is a C&MC-relevant step toward enabling multiplex transcriptional control in the CNS and other tissues under gene therapy constraints.