Application prospect of CRISPR-Cas9 gene editing in epilepsy

Abstract

Epilepsy, a chronic noncommunicable brain disorder, is characterized by abnormal electrical activity in the brain, leading to seizures and disruptions in normal brain functions. Despite various known causes, a significant proportion of epilepsy cases remain unexplained. In recent years, Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR-Cas9) technology has emerged as a powerful tool for genetic engineering. Compared with the first two generations of gene-editing technology, it has the advantages of low cost, easy design and easy operation. Utilizing CRISPR activation (CRISPRa), researchers have explored the potential of increasing the expression of genes involved in regulating synaptic interactions to control epileptic activity. Studies on transgenic mice have shown that upregulating the Kv1.1 gene (Kcnal1), which encodes for a voltage-gated potassium channel responsible for regulating neuronal excitability, can reduce seizures and improve cognitive function. Additionally, CRISPR-Cas9 has been instrumental in creating animal models to study epilepsy, providing insights into gene functions, disease mechanisms, and potential therapeutic interventions. However, further research is needed to fully explore the potential of CRISPR-based therapies for targeted treatment of epilepsy. This review systematically introduces the pathogenesis of epilepsy, including the origins and causes of epilepsy and the mechanism of seizure formation and further discusses the application of the CRISPR/Cas9 system in epilepsy.