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.M. 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. [10.2174/1566523215666150929111400]

Stem cell-mediated exon skipping of the dystrophin gene by the bystander effect

M. Meregalli;A. Farini;P. Razini;CASSINELLI, LETIZIA MARIA;F. Colleoni;FRATTINI, PAOLA;N. Santo;M. Belicchi;Y. Torrente
2015-09-29

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.
Settore MED/26 - Neurologia
CURRENT GENE THERAPY
Article (author)
File in questo prodotto:
Non ci sono file associati a questo prodotto.
Pubblicazioni consigliate

Caricamento pubblicazioni consigliate

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/323142
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 3
  • ???jsp.display-item.citation.isi??? 2
social impact