AAV-VCPi2-OptVCP

**AAV-VCPi2-OptVCP** is an investigational dual-function adeno-associated virus gene therapy for **multisystem proteinopathy 1** caused by dominant gain-of-function variants in the **VCP** gene, including the R155H variant. The AAVMYO myotropic AAV9-derived vector delivers a VCP-targeting microRNA construct, VCPi2, to partially reduce endogenous VCP expression while simultaneously expressing codon-optimized wild-type VCP to preserve total functional VCP protein. This gene-silencing plus gene-replacement strategy is intended to normalize pathological VCP activity without complete depletion of the essential VCP ATPase, thereby improving proteostasis, autophagy-related biomarkers, and TDP-43 accumulation. The program has been evaluated preclinically in patient-derived R155H skeletal muscle progenitor cells and VcpR155H/R155H knock-in mice.

Other names

VCPi2 + OptVCP