Targeted Gene Editing of a Harmful SCN8A Mutation May Prevent Seizures and Death in Mice

Allele-specific editing of a pathogenic transcript achieved a disruption rate of 1/4 to 1/3 in a mouse model of DEE.

• The sodium channel gene SCN8A has over 450 de novo missense variants associated with developmental and epileptic encephalopathies.
• A mouse model was used to study the effects of a specific variant, p.Asn1768Asp, on neuronal function.
• Editing of the pathogenic transcript resulted in out-of-frame changes that effectively reduced lethality and seizures in the model.
• Neuronal hyperexcitability decreased in cells treated with the editing virus.

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