Antisense oligonucleotides in rare neurogenetic disorders

Rapid advancements in genetic testing have significantly improved the diagnosis of rare diseases. However, the development of targeted therapies has progressed more slowly, leaving most conditions without effective treatment. Because 80% of rare genetic disorders involve the nervous system, early intervention is crucial, particularly in pediatric patients with progressive conditions. Antisense oligonucleotides (ASOs) have emerged as promising therapeutics that offer precise modulation of gene expression through RNA targeting, without requiring viral delivery systems. These therapies have been successful in modulating disease trajectories, thereby demonstrating the potential of precision medicine. Recent innovations in ASO chemical modifications and delivery strategies have enhanced their safety, stability, and tissue specificity, broadening their applicability in complex neurogenetic disorders. This review explores the mechanisms, clinical applications, and future potential of ASOs, and emphasizes their growing role in precision medicine. As diagnostics evolve alongside therapeutics, ASOs are expected to become key pillars for addressing unmet medical needs and transforming the management of previously untreatable neurogenetic disorders.