Duchenne muscular dystrophy (DMD) is a severe muscle wasting disorder caused by 
mutations in the DMD gene, affecting 1 in 3500 newborn males. Complete loss of 
muscle dystrophin protein causes progressive muscle weakness and heart and 
respiratory failure, leading to premature death. Antisense oligonucleotides 
(AONs) that bind to complementary sequences of the dystrophin pre-mRNA to induce 
skipping of the targeted exon by modulating pre-mRNA splicing are promising 
therapeutic agents for DMD. Such AONs can restore the open reading frame of the 
DMD gene and produce internally deleted, yet partially functional dystrophin 
protein isoforms in skeletal muscle. Within the last few years, clinical trials 
using AONs have made considerable progress demonstrating the restoration of 
functional dystrophin protein and acceptable safety profiles following both 
local and systemic delivery in DMD patients. However, improvement of AON 
delivery and efficacy, along with the development of multiple AONs to treat as 
many DMD patients as possible needs to be addressed for this approach to fulfill 
its potential. Here, we review the recent progress made in clinical trials using 
AONs to treat DMD and discuss the current challenges to the development of 
AON-based therapy for DMD.