Antisense Oligonucleotide Gene Therapy for Neuromuscular Disorders

Abstract

Antisense oligonucleotides (ASOs) are synthetic, single-stranded DNA molecules that can bind to specific mRNA sequences and alter protein expression. ASO gene therapies are leading to breakthroughs in the treatment of once intractable neuromuscular disorders. In 2016, ASOs became the first FDA-approved drugs for treating spinal muscular atrophy and Duchenne muscular dystrophy. Recent trials also suggest ASOs may be effective in combating Huntington’s disease, amyotrophic lateral sclerosis and hereditary transthyretin amyloidosis. This article highlights ASOs’ mechanism of action, their use in treating neuromuscular disease and future obstacles the gene therapy must overcome, providing an update on the state of ASO technology.