AAV-N-miRhUBE3A-ATS

AAV-N-miRhUBE3A-ATS is an experimental gene therapy candidate developed by Encoded Therapeutics for the treatment of Angelman syndrome. It utilizes an engineered AAV9 capsid variant, designated AAV-N, which is optimized for crossing the blood-brain barrier following systemic intravenous administration. The therapeutic payload consists of a vectorized microRNA (miRNA) designed to selectively target and knock down the long non-coding RNA UBE3A-ATS. In neurons, UBE3A-ATS normally silences the paternal copy of the UBE3A gene; by knocking down this transcript, AAV-N-miRhUBE3A-ATS unsilences the paternal allele, restoring UBE3A protein expression to compensate for the loss-of-function maternal allele that causes the disorder. Preclinical studies in non-human primates have demonstrated broad neuronal transduction and significant target engagement without adverse findings.