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.
Stem cell-mediated exon skipping of the dystrophin gene by the bystander effect / M. Meregalli, A. Farini, C. Sitzia, C. Beley, P. Razini, L. Cassinelli, F. Colleoni, P. Frattini, N. Santo, E. Galbiati, D. Prosperi, A. Tavelli, M. Belicchi, L. Garcia, Y. Torrente. - In: CURRENT GENE THERAPY. - ISSN 1566-5232. - 15:6(2015 Sep 29), pp. 563-571.
|Titolo:||Stem cell-mediated exon skipping of the dystrophin gene by the bystander effect|
|Settore Scientifico Disciplinare:||Settore MED/26 - Neurologia|
|Data di pubblicazione:||29-set-2015|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.2174/1566523215666150929111400|
|Appare nelle tipologie:||01 - Articolo su periodico|