Rare variants in genes GRIN2A, GRIN2B and GRIN2D are associated with severe childhood-onset neurological diseases like epileptic encephalopathies and autism. There are no treatments for these chronic disorders that cause developmental delays or developmental skill loss. Researcher and principal investigator, Scott Harper, at Nationwide Children’s Hospital developed a genetic therapy for GRIN2 disease through a knockdown-and-replace strategy by using artificial microRNAs that non-selectively knockdown both mutant and wildtype GRIN2A alleles using RNAi and adding back an RNAi-resistant, wildtype GRIN2A cDNA. The therapy will express functional GRIN2 exogenously while eliminating endogenous GRIN2 mRNA entirely through AAV delivery.