AAV-amiR-SOD1 for the treatment of ALS in mice

Adeno-associated virus (AAV)-mediated gene silencing offers a promising strategy for achieving durable therapeutic effects with a single administration. Mutations in the Superoxide Dismutase 1 (SOD1) gene, inherited in an autosomal dominant manner, lead to motor neuron degeneration in amyotrophic lateral sclerosis (ALS), a fatal neurodegenerative disease with no effective treatment. In this study, we employed AAV9 to deliver an artificial microRNA targeting SOD1, embedded in dual miR-33 scaffolds driven by the promoter of the human survival motor neuron 1 (hSMN1) gene, in the SOD1G93A mouse model of ALS.