Oligonucleotides as a Novel Therapeutic Approach: An Innovative Area for Drug Delivery in Neurological Disorders
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Abstract
RNA-based therapeutics have emerged as one of the most potent therapeutic options used for the modulation of gene/protein expression and gene editing with the potential to treat neurodegenerative diseases. However, the delivery of nucleic acids to the central nervous system (CNS) by the systemic route, remains a major hurdle.
To overcome this pitfall, this review focuses on oligonucleotide-based novel strategies including liposomes, carbon nanotubes, quantum dots, solid lipid nanoparticles, nano lipid carriers, polymeric nanoparticles, mesoporous silica, dendrimers, aptamers, nanobodies etc. These strategies are designed to overcome these barriers by different pathways and mechanisms of transport across the blood−brain barrier. Ongoing preclinical and clinical studies are assessing the safety and efficacy of Antisense Oligonucleotide) ASOs (in multiple genetic and acquired neurological conditions. The current review provides an update on novel approaches, preclinical, clinical evidence, and delivery route of ASOs. The administration of FDA-approved ASOs in neurological disorders is also described. The current evidence on the safety and efficacy of ASOs in brain diseases will help identify opportunities for a broader range of nucleic acids and accelerate the clinical translation of these innovative therapies.
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