Duchenne muscular dystrophy (DMD) is characterized by the loss of a functional dystrophin protein. By using antisense oligonucleotides (AONs), it is possible to modulate pre-mRNA splicing, eliminating mutated exons and restoring dystrophin open reading frame. To overcome the hurdles in using AONs for therapeutic interventions, the authors of this study exerted engineered human DMD stem cells with a lentivirus, which permanently and efficiently delivered the cloned AONs. Here, they describe for the first time the exosome-mediated release of AONs from engineered human DMD CD133+ stem cells allowing the rescue of murine dystrophin expression. Finally, upon release, AONs could be internalized by host cells, suggesting a potential role of exosomes acting as vesicular carriers for DMD gene therapy.
