AAV6MT-iCasp9

AAV6MT-iCasp9 is a preclinical gene therapy construct designed as a safety mechanism for muscle-directed gene therapies, particularly those targeting Duchenne muscular dystrophy (DMD). It utilizes a muscle-tropic adeno-associated virus serotype 6 (AAV6MT) capsid, which incorporates tyrosine-to-phenylalanine mutations (Y445F and Y731F) to enhance transduction efficiency in skeletal and cardiac muscle by avoiding proteasomal degradation. The vector delivers an inducible Caspase 9 (iCasp9) safety switch, consisting of a modified human caspase 9 fused to a drug-binding domain (FKBP12). This system remains dormant until the administration of a small-molecule chemical inducer of dimerization (CID), such as rimiducid (AP1903). Upon dimerization, the iCasp9 protein initiates the apoptotic cascade, allowing for the selective elimination of transduced cells if adverse events occur or if the therapeutic effect is no longer needed.

Other names

AAV6-MT-iCasp9AAV-6-MT-iCasp9AAV 6-MT-iCasp9AAV6(Y445F+Y731F)-iCasp9AAV6-iCasp9AAV-6-iCasp9AAV 6-iCasp9