Exon skipping is a therapeutic approach for Duchenne muscular dystrophy (DMD) 
that has been in development for close to two decades. This approach uses 
antisense oligonucleotides (AONs) to modulate pre-mRNA splicing of dystrophin 
transcripts to restore the disrupted DMD reading frame. The approach has moved 
from in vitro proof of concept studies to the clinical trial phase and marketing 
authorization applications with regulators. The first AON (eteplirsen) has 
recently received accelerated approval by the Food and Drug Administration in 
the US. Areas covered: In this review the authors explain the antisense-mediated 
exon skipping approach, outline how it needs be tailored for different DMD 
mutation types and describe the challenges and opportunities for each mutation 
type. The authors summarize the clinical development of antisense-mediated exon 
51 skipping, and discuss methods to improve efficiency. Finally, the authors 
provide their opinion on current developments and identify topics for future 
prioritization. Expert opinion: Exon skipping development has been a learning 
experience for all those involved. Aside from an approved therapy, its 
development has yielded side benefits including the development of tools for 
clinical trials and has increased collaboration between academics, patients, 
industry and regulators.