MyoAAV-KDAR

MyoAAV-KDAR is an experimental gene therapy candidate designed for the treatment of Nemaline Myopathy 3 (NEM3), a severe congenital neuromuscular disorder caused by mutations in the skeletal muscle α-actin (ACTA1) gene. Developed by researchers at Nationwide Children's Hospital and The Ohio State University, the therapy utilizes a muscle-tropic MyoAAV vector to deliver a dual-function "KnockDown And Replacement" (KDAR) genetic construct. This construct simultaneously employs RNA interference (miRNA) to silence the expression of endogenous mutant ACTA1 mRNA and provides a codon-optimized, RNAi-resistant version of the ACTA1 gene (rACTA1) to restore functional protein levels. The expression of the replacement gene is driven by the muscle-specific MHCK7 promoter. This mutation-independent approach is intended to be applicable across all autosomal dominant ACTA1 variants, aiming to reduce nemaline rod accumulation and improve muscle strength and function.