AAV-SLB101.mi405

AAV-SLB101.mi405 is an experimental gene therapy candidate designed for the treatment of Facioscapulohumeral muscular dystrophy (FSHD). It utilizes the next-generation AAV-SLB101 capsid, engineered by Solid Biosciences for enhanced muscle tropism (myotropism) and reduced liver uptake (liver detargeting), to deliver mi405, an artificial microRNA (miRNA) targeting the DUX4 gene. FSHD is an autosomal dominant disorder caused by the toxic de-repression of DUX4 in skeletal muscle, which leads to muscle cell dysfunction and progressive dystrophy. By delivering mi405, the therapy aims to silence DUX4 expression through RNA interference (RNAi). Preclinical studies in the TIC-DUX4 mouse model have demonstrated that AAV-SLB101.mi405 can achieve significant molecular, histopathological, and functional improvements at doses up to one log lower than first-generation AAV vectors, potentially offering a safer and more effective therapeutic profile.