| DOI | Trouver le DOI : https://doi.org/10.1006/mthe.2002.0723 |
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| Auteur | Rechercher : Danialou, Gawiyou; Rechercher : Comtois, Alain; Rechercher : Dudley, Roy; Rechercher : Nalbantoglu, Josephine; Rechercher : Gilbert, Rénald; Rechercher : Karpati, George; Rechercher : Jones, David H.; Rechercher : Petrof, Basil J. |
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| Format | Texte, Article |
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| ISSN | 1525-0016 |
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| Sujet | beta-galactosidase; chemiluminescent measurements; DNA; gene therapy; gene transfer techniques; hyaluronoglucosaminidase; mice; mice, inbred C57BL; mice, inbred mdx; muscles; muscular dystrophies; plasmids; ultrasonics |
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| Résumé | Studies have shown that ultrasound, used either alone or in combination with microbubble contrast agents, can increase cell membrane permeability to plasmid DNA. Because ultrasound is a non-painful and well-established tool in clinical medicine, its potential to enhance DNA uptake into the muscles of patients with muscular dystrophy is conceptually attractive. Therefore, we evaluated the ability of ultrasound pulses (1 MHz; 1.5 W/cm2) to increase exogenous (LacZ) gene expression in normal wild-type and dystrophic Dmd(mdx/mdx) mice after plasmid DNA injection into muscle. We also ascertained whether co-injection of lipid-encapsulated perfluoropropane microbubbles (Definity) or pretreatment with hyaluronidase could further increase the level of gene transfer to ultrasound-treated muscles. The use of ultrasound did not increase transfection efficiency in normal mice. In contrast, dystrophic mice demonstrated an increase in the number of transfected fibers (threefold) as well as the amount of LacZ protein (22-fold) after ultrasound exposure, provided that Definity was also co-injected with the DNA. Pretreatment of muscles with hyaluronidase before ultrasound exposure was not effective in augmenting the level of gene transfer. Under the optimal conditions for dystrophic muscle transfection (ultrasound + Definity), there was no associated increase in muscle damage. Hence ultrasound may provide a safe and effective method for enhancing gene transfer to dystrophic muscles, thereby increasing the prospects for therapeutic application of naked DNA in muscular dystrophy patients. |
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| Date de publication | 2002-11-01 |
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| Maison d’édition | American Society of Gene Therapy/Elsevier |
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| Dans | |
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| Publications évaluées par des pairs | Oui |
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| Publication du CNRC | Cette publication n’est pas du CNRCCe sont des publications qui ont été rédigées par un auteur du CNRC, mais avant que celui-ci soit employé du CNRC. |
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| Numéro NPARC | 12339198 |
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| Exporter la notice | Exporter en format RIS |
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| Signaler une correction | Signaler une correction (s'ouvre dans un nouvel onglet) |
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| Identificateur de l’enregistrement | 954eaae7-c3af-4b63-b961-4d157433a14a |
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| Enregistrement créé | 2009-09-11 |
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| Enregistrement modifié | 2021-09-17 |
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