Iyer, Pavithra S.Mavoungou, Lionel O.Ronzoni, FlavioZemla, JoannaSchmid-Siegert, EmanuelAntonini, StefaniaNeff, Laurence A.Dorchies, Olivier M.Jaconi, MarisaLekka, MalgorzataMessina, GraziellaMermod, Nicolas2018-12-132018-12-132018-12-132018-04-0410.1016/j.ymthe.2018.01.021https://infoscience.epfl.ch/handle/20.500.14299/152656WOS:000431483400017Duchenne muscular dystrophy (DMD) is a lethal muscle-wasting disease currently without cure. We investigated the use of the PiggyBac transposon for full-length dystrophin expression in murine mesoangioblast (MABs) progenitor cells. DMD murine MABs were transfected with transposable expression vectors for full-length dystrophin and transplanted intramuscularly or intra-arterially into mdx/SCID mice. Intraarterial delivery indicated that the MABs could migrate to regenerating muscles to mediate dystrophin expression. Intramuscular transplantation yielded dystrophin expression in 11%-44% of myofibers in murine muscles, which remained stable for the assessed period of 5 months. The satellite cells isolated from transplanted muscles comprised a fraction of MAB-derived cells, indicating that the transfected MABs may colonize the satellite stem cell niche. Transposon integration site mapping by whole-genome sequencing indicated that 70% of the integrations were intergenic, while none was observed in an exon. Muscle resistance assessment by atomic force microscopy indicated that 80% of fibers showed elasticity properties restored to those of wild-type muscles. As measured in vivo, transplanted muscles became more resistant to fatigue. This study thus provides a proof-of-principle that PiggyBac transposon vectors may mediate full-length dystrophin expression as well as functional amelioration of the dystrophic muscles within a potential autologous cell-based therapeutic approach of DMD.Biotechnology & Applied MicrobiologyGenetics & HeredityMedicine, Research & ExperimentalBiotechnology & Applied MicrobiologyGenetics & HeredityResearch & Experimental Medicinemuscle stem-cellsmouse modelgenetic correctionmdx mouseexpressionmicemorpholinosdeliverytext::journal::journal article::research article