GENOME-BASED THERAPEUTICS TARGETING SOMATIC MOSAICISM IN NEURODEVELOPMENTAL DISORDERS

Abstract

Background: Somatic mosaicism has emerged as a major genetic contributor to neurodevelopmental disorders, including autism spectrum disorders, epilepsy, focal cortical dysplasia, and intellectual disabilities. Post-zygotic mutations occurring during brain development generate genetically distinct neuronal populations that contribute to abnormal neural circuitry and disease progression.

Objective: This study aimed to evaluate genome-based therapeutic strategies targeting somatic mosaic mutations in neurodevelopmental disorders and to assess their potential for precision neurogenomic medicine.

Methods: Advanced genome engineering technologies including CRISPR-Cas9 editing, base editing, prime editing, and antisense oligonucleotide therapies were comparatively analyzed using neural stem cells, patient-derived brain organoids, and transgenic animal models. Single-cell sequencing and functional neuronal assays were employed to assess mutation correction efficiency and therapeutic outcomes.

Findings: Genome-based therapeutic systems achieved approximately 78–91% mutation correction efficiency with significant restoration of neuronal signaling and synaptic function. Base editing platforms demonstrated the highest editing precision and reduced off-target mutation frequency compared with conventional CRISPR systems.

Conclusion: Genome-based therapeutics demonstrate substantial potential for personalized treatment of somatic mosaic neurodevelopmental disorders. Precision genome editing combined with advanced neurogenomic analysis may enable future development of targeted and clinically scalable neurological therapies.