Stem Cell-Mediated Exon Skipping of the Dystrophin Gene by the Bystander Effect

作者：Meregalli Mirella; Farini Andrea; Sitzia Clementina; Beley Cyriaque; Razini Paola; Cassinelli Letizia; Colleoni Federica; Frattini Paola; Santo Nadia; Galbiati Elisabetta; Prosperi Davide; Tavelli Alessandro; Belicchi Marzia; Garcia Luis; Torrente Yvan^*

来源：Current Gene Therapy, 2015, 15(6): 563-571.

DOI：10.2174/1566523215666150929111400

• Bystander effect
• Myogenic stem cells
• Delivery of exon skipping machinery

Duchenne muscular dystrophy (DMD) is characterized by the loss of a functional dystrophin protein; the muscles of DMD patients progressively degenerate as a result of mechanical stress during contractions, and the condition eventually leads to premature death. By means 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, we exerted engineered human DMD stem cells with a lentivirus, which permanently and efficiently delivered the cloned AONs. Here we 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.

• 出版日期2015