rAAV9-miATXN3-10x2

rAAV9-miATXN3-10x2 is an experimental gene therapy developed for the treatment of Spinocerebellar ataxia type 3 (SCA3), also known as Machado-Joseph disease. It utilizes a recombinant adeno-associated virus serotype 9 (rAAV9) vector to deliver a bicistronic artificial microRNA (miRNA) construct designed to selectively silence the mutant ATXN3 allele. The therapy specifically targets a single nucleotide polymorphism (SNP) associated with the pathogenic CAG repeat expansion in the ATXN3 gene, allowing for the reduction of toxic mutant Ataxin-3 protein while preserving the expression of the wild-type protein. Preclinical studies in mouse models and non-human primates have demonstrated widespread CNS transduction, reduction in mutant Ataxin-3 aggregates, and improvement in motor and molecular outcomes following intracisterna magna or intracerebellar administration.