CRISPR Therapies in Treating Monogenic Neurodevelopmental Disorders
TL;DR
This review evaluates the potential of CRISPR-based editing as a therapeutic strategy for monogenic NDDs and evaluates the limitations that must be addressed before its widespread application in human patients.
Abstract
Neurodevelopmental Disorders (NDDs) arise when a pathogenic gene mutation disrupts an individual’s brain development, often resulting in symptoms such as epilepsy, motor impairments, and intellectual disability. Historically, NDDs have been managed primarily through pharmacological and behavioral therapies that alleviate symptoms but do not address the underlying genetic causes. Recent advances in genomic medicine, particularly the development of Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-based technologies, have created the opportunity to directly target disease-causing genes. The versatility of CRISPR has enabled the development of multiple editing and regulatory modalities, allowing increasingly precise control of gene expression. Preclinical studies in rodent models suggest that CRISPR-mediated epigenetic reactivation may be an effective strategy for treating monogenic NDDs by restoring gene function without permanently altering the DNA sequence. While these approaches show promise, significant challenges related to delivery, safety, and ethical considerations remain. Despite these controversies surrounding the use of CRISPR, it remains a prospective candidate in improving the management of NDDs in the future. This review evaluates the potential of CRISPR-based editing as a therapeutic strategy for monogenic NDDs and evaluates the limitations that must be addressed before its widespread application in human patients.