Recent advancements, challenges and strategies of antisense oligonucleotide in drug delivery system: An overview

Antisense oligonucleotides (ASOs) are small synthetic nucleic acids designed to bind RNA and modulate gene expression. They have significant therapeutic potential for treating genetic and acquired diseases, especially in cancer and hereditary disorders. Their primary mechanisms include RNA cleavage, mediated by RNase H1 or RNA interference (RNAi), and RNA blockage via steric hindrance or splice modulation. First-generation modifications, such as phosphorothioate linkage, and more advanced forms like locked nucleic acids (LNA) and peptide nucleic acids (PNA) have improved their pharmacokinetics and binding affinity. ASOs have achieved success in treating diseases like spinal muscular atrophy and Duchenne muscular dystrophy, with several FDA-approved drugs.