Abstract
Genetic neuromuscular diseases are caused by defective expression of nuclear or mitochondrial genes. Toxic mutant protein may cause cell death, and thus, strategies that reduce mutant gene expression may provide therapeutic benefit. Synthetic antisense oligonucleotide (ASO) has been known to recognize cellular RNA and control gene expression. In recent years, advances in ASO chemistry, creation of designer ASO molecules to enhance their delivery and safety, and design of clinical trials to judge therapeutic efficacy have ushered into an era of plausible application of ASO technology to treat currently incurable neuromuscular diseases. The US Food and Drug Administration has recently approved two ASO therapies in genetic neuromuscular diseases. This brief overview examines the recent advances in ASO technology, evolution, and use of synthetic ASOs as therapeutic platform, and the mechanism of ASO action by exon-inclusion in spinal muscular atrophy and exon-skipping in Duchenne muscular dystrophy, with attention to their advantages and limitations.