A PiggyBac-mediated approach for muscle gene transfer or cell therapy.

Détails

ID Serval
serval:BIB_F2194B4273DB
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
A PiggyBac-mediated approach for muscle gene transfer or cell therapy.
Périodique
Stem Cell Research
Auteur(s)
Ley D., Van Zwieten R., Puttini S., Iyer P., Cochard A., Mermod N.
ISSN
1876-7753 (Electronic)
Statut éditorial
Publié
Date de publication
2014
Volume
13
Numéro
3 Pt A
Pages
390-403
Langue
anglais
Résumé
An emerging therapeutic approach for Duchenne muscular dystrophy is the transplantation of autologous myogenic progenitor cells genetically modified to express dystrophin. The use of this approach is challenged by the difficulty in maintaining these cells ex vivo while keeping their myogenic potential, and ensuring sufficient transgene expression following their transplantation and myogenic differentiation in vivo. We investigated the use of the piggyBac transposon system to achieve stable gene expression when transferred to cultured mesoangioblasts and into murine muscles. Without selection, up to 8% of the mesoangioblasts expressed the transgene from 1 to 2 genomic copies of the piggyBac vector. Integration occurred mostly in intergenic genomic DNA and transgene expression was stable in vitro. Intramuscular transplantation of mouse Tibialis anterior muscles with mesoangioblasts containing the transposon led to sustained myofiber GFP expression in vivo. In contrast, the direct electroporation of the transposon-donor plasmids in the mouse Tibialis muscles in vivo did not lead to sustained transgene expression despite molecular evidence of piggyBac transposition in vivo. Together these findings provide a proof-of-principle that piggyBac transposon may be considered for mesoangioblast cell-based therapies of muscular dystrophies.
Pubmed
Web of science
Création de la notice
15/12/2014 15:14
Dernière modification de la notice
03/03/2018 22:39
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