Abstract
RNA therapeutics are a revolutionary drug platform that can regulate the expression and splicing of specific genes. With the technological advances in chemical modification and ligand conjugation, RNA therapeutics have been successively approved for the treatment of neuromuscular diseases that were considered intractable. However, the lack of efficacy, safety, and DDS have hindered further clinical application. To overcome these issues, intensive researches have been conducted at the clinical and preclinical levels. In this article, we review these efforts, particularly in the area of RNA therapeutics for neuromuscular diseases. For central nervous system（CNS） targeting, we review gapmer antisense oligonucleotides that cross the blood-brain barrier and siRNAs that have achieved excellent distribution in the CNS by intrathecal administration. For muscle targeting, I would like to present the latest findings on splice-switch oligonucleotides to improve DDS in cardiac and skeletal muscles at the clinical and preclinical levels.
