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Stem Cell-Mediated Exon Skipping of the Dystrophin Gene by the Bystander Effect.
- Source :
-
Current gene therapy [Curr Gene Ther] 2015; Vol. 15 (6), pp. 563-71. - Publication Year :
- 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.
- Subjects :
- Animals
Bystander Effect physiology
Cells, Cultured
Dystrophin biosynthesis
Exons genetics
Humans
Mice
Mice, SCID
Muscle, Skeletal pathology
Oligonucleotides, Antisense genetics
RNA Splicing genetics
Dystrophin genetics
Genetic Therapy methods
Muscular Dystrophy, Duchenne genetics
Muscular Dystrophy, Duchenne therapy
Stem Cells cytology
Subjects
Details
- Language :
- English
- ISSN :
- 1875-5631
- Volume :
- 15
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Current gene therapy
- Publication Type :
- Academic Journal
- Accession number :
- 26415573
- Full Text :
- https://doi.org/10.2174/1566523215666150929111400