Titre :
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Ex vivo gene therapy for Duchenne muscular dystrophy : lentiviral and PhiC31 integrase approaches (abstract : congrès international de Myologie, 2005)
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contenu dans :
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Auteurs :
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Congrès international de myologie 2005 (International Congress of Myology 2005; 9-13 mai 2005; Nantes, France) ;
Quenneville SP ;
Chapdelaine P ;
Calos M ;
Tremblay J
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Type de document :
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Article
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Année de publication :
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2005
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Pages :
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p. 273
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Langues:
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Anglais
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Mots-clés :
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colloque
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culture cellulaire
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dystrophie musculaire de Duchenne
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dystrophine
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intégrase
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muscle squelettique
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prise en charge thérapeutique
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thérapie cellulaire
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thérapie génique
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vecteur lentiviral
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Résumé :
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Communication n° 425 Introduction : Duchenne Muscular Dystrophy (DMD) is the most severe muscular dystrophy. It is caused by the absence of dystrophin in muscle fibers. This absence leads to increased muscle damage. Myogenic cell transplantation is a possible treatment for DMD. Objectives : Autologous myogenic cell transplantation would permit to avoid the use immunosupression. Thus the main objective of our research project is to find a safe method to genetically modify the cells from a dystrophic patient in vitro and transfer the transgene expression into the muscle fibers using cell transplantation. Method : CMVeGFP, CMVeGFP-microdystrophin and MCK-eGFPMicrodystrophin cassettes were introduced into human and mouse myogenic cells using lentiviral vectors. A non-viral technique was also essayed. A plasmid containing eGFP or the eGFP-Dystrophin transgene was co-nucleofected into human myoblasts with a plasmid expressing the PhiC31 integrase. Cells genetically modified with both methods were transplanted into mouse muscles. Results : The expression of dystrophin was stabilized using PhiC31 integrase. The expression of the transgene was detected one month after the transplantation. The lentiviral method was also effective. Cells were infected and transplanted. Using the MCK-eGFPMicrodystrophin lentiviral vector, the transgene was detected one month after the transplantation of the genetically modified cells into mouse recipients. Conclusions : The use of nucleofection/PhiC31 technique and of the lentiviral vector are effective methods to genetically modify cultured myoblasts. The transplantation of ex vivo genetically modified cells is a safe method to express a transgene into the dystrophic muscle.
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