KCNC1-related epilepsy is a severe developmental and epileptic encephalopathy (DEE) caused by a mutation in the KCNC1 gene encoding Kv3.1, a voltage-gated potassium channel subunit. Patients harboring the recurrent pathogenic variant KCNC1-p.Ala421Val (A421V) have spontaneous seizures and moderate-to-severe developmental delay/intellectual disability. The advent of genetic therapies like the antisense-oligonucleotide (ASO), a short synthetic strand of nucleic acid designed to bind target RNA sequences and modulate their expression, opens new opportunities for treatment of KCNC1-related epilepsy. The aim of this study is to assess the efficacy of an ASO that specifically targets and degrades Kv3.1 protein transcripts in a mouse model heterozygously expressing the A421V variant. Survival and ataxia severity as a behavioral phenotype of the Kcnc1-A421V/+ mutants were assessed using hindlimb clasping and ledge walking tests in both WT and mutant genotypes from weeks 5 – 11 after ASO or PBS (control) injections at P0-3. We found promising data suggesting that survival is increased and ataxia is less severe at earlier timepoints in ASO-injected Kcnc1-A421V/+ mice. Future directions include expanding cohort size, administering the ASO at a higher dosage, and testing better ASOs with a higher in vitro knockdown of Kv3.1. Significant improvements in ataxia in these mice could make the ASO a promising therapy for future clinical trials in KCNC1-related epilepsy.