Stem Cell-Mediated Exon Skipping of the Dystrophin Gene by the Bystander Effect.
Curr Gene Ther
; 15(6): 563-71, 2015.
Article
em En
| MEDLINE
| ID: mdl-26415573
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.
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Bases de dados:
MEDLINE
Assunto principal:
Células-Tronco
/
Terapia Genética
/
Distrofina
/
Distrofia Muscular de Duchenne
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Curr Gene Ther
Assunto da revista:
GENETICA MEDICA
/
TERAPEUTICA
Ano de publicação:
2015
Tipo de documento:
Article