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.

Meregalli, M., Farini, A., Sitzia, C., Beley, C., Razini, P., Cassinelli, L., et al. (2015). Stem Cell-Mediated Exon Skipping of the Dystrophin Gene by the Bystander Effect. CURRENT GENE THERAPY, 15(6), 563-571 [10.2174/1566523215666150929111400].

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

CASSINELLI, LETIZIA MARIA;GALBIATI, ELISABETTA;PROSPERI, DAVIDE;
2015

Abstract

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.
Articolo in rivista - Articolo scientifico
Bystander effect; Myogenic stem cells; Delivery of exon skipping machinery
English
563
571
9
Meregalli, M., Farini, A., Sitzia, C., Beley, C., Razini, P., Cassinelli, L., et al. (2015). Stem Cell-Mediated Exon Skipping of the Dystrophin Gene by the Bystander Effect. CURRENT GENE THERAPY, 15(6), 563-571 [10.2174/1566523215666150929111400].
Meregalli, M; Farini, A; Sitzia, C; Beley, C; Razini, P; Cassinelli, L; Colleoni, F; Frattini, P; Santo, N; Galbiati, E; Prosperi, D; Tavelli, A; Belicchi, M; Garcia, L; Torrente, Y
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10281/100119
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