AAV-Cas12a

AAV-Cas12a is an experimental gene therapy platform that utilizes adeno-associated virus (AAV) vectors to deliver the CRISPR-Cas12a genome editing system. This specific implementation, developed by researchers at the University of Massachusetts Chan Medical School and the University of Missouri, incorporates a multilayer RNA switch to provide tight temporal control over Cas12a expression. The system remains dormant until activated by a steric-blocking antisense oligonucleotide (ASO), which triggers the simultaneous release of regulatory layers governing protein expression and guide RNA (crRNA) maturation. To optimize performance, a split inducible Cas12a architecture was engineered, demonstrating significant efficiency in inducing exon 23 skipping in the dystrophin gene within mdx mouse models of Duchenne muscular dystrophy (DMD). This approach aims to mitigate safety risks associated with persistent CRISPR expression, such as off-target editing and immune responses.

Other names

RNA switch-regulated CRISPR-Cas12asplit inducible Cas12a system