title: Restoration of human dystrophin following transplantation of exon-skipping-engineered DMD patient stem cells into dystrophic mice.
abstract: 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.
authors: Stem Cell Laboratory, Department of Neurological Sciences, Fondazione IRCCS Ospedale Maggiore Policlinico, Centro Dino Ferrari, University of Milan, via F. Sforza 35, 20122 Milan, Italy.
authors: Rachid
authors: R
authors: Benchaouir
authors: Mirella
authors: M
authors: Meregalli
authors: Andrea
authors: A
authors: Farini
authors: Giuseppe
authors: G
authors: D'Antona
authors: Marzia
authors: M
authors: Belicchi
authors: Aurélie
authors: A
authors: Goyenvalle
authors: Maurizio
authors: M
authors: Battistelli
authors: Nereo
authors: N
authors: Bresolin
authors: Roberto
authors: R
authors: Bottinelli
authors: Luis
authors: L
authors: Garcia
authors: Yvan
authors: Y
authors: Torrente
mesh_terms: D000071916:AC133 Antigen; D000818:Animals; D015703:Antigens, CD / Q000235:genetics; D002478:Cells, Cultured; D016189:Dystrophin / Q000235:genetics* / Q000378:metabolism; D005091:Exons; D017353:Gene Deletion; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D006023:Glycoproteins / Q000235:genetics; D006801:Humans; D016086:Lentivirus / Q000235:genetics; D051379:Mice; D018101:Mice, Inbred mdx; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D009137:Muscular Dystrophy, Animal / Q000235:genetics / Q000628:therapy*; D020388:Muscular Dystrophy, Duchenne / Q000235:genetics*; D010455:Peptides / Q000235:genetics; D033581:Stem Cell Transplantation; D014183:Transplantation, Heterologous
chemical_list: D000071916:AC133 Antigen; D015703:Antigens, CD; D016189:Dystrophin; D006023:Glycoproteins; C000606023:PROM1 protein, human; D010455:Peptides; C000606024:Prom1 protein, mouse