TY - JOUR
T1 - Stem cell-mediated exon skipping of the dystrophin gene by the bystander effect
AU - Meregalli, Mirella
AU - Farini, Andrea
AU - Sitzia, Clementina
AU - Beley, Cyriaque
AU - Razini, Paola
AU - Cassinelli, Letizia
AU - Colleoni, Federica
AU - Frattini, Paola
AU - Santo, Nadia
AU - Galbiati, Elisabetta
AU - Prosperi, Davide
AU - Tavelli, Alessandro
AU - Belicchi, Marzia
AU - Garcia, Luis
AU - Torrente, Yvan
PY - 2015/12/1
Y1 - 2015/12/1
N2 - 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.
AB - 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.
KW - Bystander effect
KW - Delivery of exon skipping machinery
KW - Myogenic stem cells
UR - http://www.scopus.com/inward/record.url?scp=84947923771&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84947923771&partnerID=8YFLogxK
M3 - Article
C2 - 26415573
AN - SCOPUS:84947923771
VL - 15
SP - 563
EP - 571
JO - Current Gene Therapy
JF - Current Gene Therapy
SN - 1566-5232
IS - 6
ER -