A hit for base editing: treatment of developmental epilepsy in a mouse model

J Clin Invest. 2026 Feb 2;136(3):e200689. doi: 10.1172/JCI200689.

Abstract

CRISPR/Cas9 base editing holds the potential to treat disease caused by single-nucleotide variants. In contrast with conventional CRISPR/Cas9 approaches, base editing enzymatically induces precise DNA alterations and can directly correct disease-causing variants. In this issue of JCI, Reever et al. used base editing to treat a mouse model of a severe neurodevelopmental disorder caused by a pathogenic missense variant in the voltage-gated sodium channel gene SCN8A. This work represents a starting point for the further refinement of base editing to treat genetic epilepsy.

MeSH terms

  • Animals
  • CRISPR-Cas Systems*
  • Disease Models, Animal
  • Epilepsy* / genetics
  • Epilepsy* / therapy
  • Gene Editing*
  • Genetic Therapy*
  • Humans
  • Mice
  • Mutation, Missense
  • NAV1.6 Voltage-Gated Sodium Channel* / genetics
  • NAV1.6 Voltage-Gated Sodium Channel* / metabolism

Substances

  • NAV1.6 Voltage-Gated Sodium Channel