miG2a

miG2a is an experimental RNA interference (RNAi) gene therapy designed for the treatment of developmental and epileptic encephalopathy (DEE) caused by gain-of-function mutations in the *GRIN2A* gene. The therapeutic consists of a microRNA (miRNA) sequence that targets conserved regions of both mouse and human *GRIN2A* mRNA, packaged within a self-complementary adeno-associated virus serotype 9 (AAV9) vector under the control of a U6 promoter. By knocking down the expression of the pathogenic *GRIN2A* protein, miG2a aims to reduce the toxic effects of the gain-of-function variants. In preclinical studies using *Grin2a* S644G mouse models, neonatal intracerebroventricular administration of miG2a significantly extended survival and restored seizure thresholds, although it showed limited efficacy in reversing behavioral phenotypes such as hyperactivity.