TY - JOUR
T1 - Restoration of Human Dystrophin Following Transplantation of Exon-Skipping-Engineered DMD Patient Stem Cells into Dystrophic Mice
AU - Benchaouir, Rachid
AU - Meregalli, Mirella
AU - Farini, Andrea
AU - D'Antona, Giuseppe
AU - Belicchi, Marzia
AU - Goyenvalle, Aurélie
AU - Battistelli, Maurizio
AU - Bresolin, Nereo
AU - Bottinelli, Roberto
AU - Garcia, Luis
AU - Torrente, Yvan
PY - 2007/12/13
Y1 - 2007/12/13
N2 - Duchenne muscular dystrophy (DMD) is a hereditary disease caused by mutations that disrupt the dystrophin mRNA reading frame. In some cases, forced exclusion (skipping) of a single exon can restore the reading frame, giving rise to a shorter, but still functional, protein. In this study, we constructed lentiviral vectors expressing antisense oligonucleotides in order to induce an efficient exon skipping and to correct the initial frameshift caused by the DMD deletion of CD133+ stem cells. The intramuscular and intra-arterial delivery of genetically corrected CD133 expressing myogenic progenitors isolated from the blood and muscle of DMD patients results in a significant recovery of muscle morphology, function, and dystrophin expression in scid/mdx mice. These data demonstrate that autologous engrafting of blood or muscle-derived CD133+ cells, previously genetically modified to reexpress a functional dystrophin, represents a promising approach for DMD.
AB - Duchenne muscular dystrophy (DMD) is a hereditary disease caused by mutations that disrupt the dystrophin mRNA reading frame. In some cases, forced exclusion (skipping) of a single exon can restore the reading frame, giving rise to a shorter, but still functional, protein. In this study, we constructed lentiviral vectors expressing antisense oligonucleotides in order to induce an efficient exon skipping and to correct the initial frameshift caused by the DMD deletion of CD133+ stem cells. The intramuscular and intra-arterial delivery of genetically corrected CD133 expressing myogenic progenitors isolated from the blood and muscle of DMD patients results in a significant recovery of muscle morphology, function, and dystrophin expression in scid/mdx mice. These data demonstrate that autologous engrafting of blood or muscle-derived CD133+ cells, previously genetically modified to reexpress a functional dystrophin, represents a promising approach for DMD.
KW - HUMDISEASE
KW - STEMCELL
UR - http://www.scopus.com/inward/record.url?scp=36749032678&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=36749032678&partnerID=8YFLogxK
U2 - 10.1016/j.stem.2007.09.016
DO - 10.1016/j.stem.2007.09.016
M3 - Article
C2 - 18371406
AN - SCOPUS:36749032678
VL - 1
SP - 646
EP - 657
JO - Cell Stem Cell
JF - Cell Stem Cell
SN - 1934-5909
IS - 6
ER -