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A differential efficiency of adenovirus-mediated in vivo gene transfer into skeletal muscle cells of different maturity
Authors:Acsadi, Gyula   Jani, Agnes   Massie, Bernard   Simoneau, Maude   Holland, Paul   Blaschuk, Katharine   Karpati, George
Affiliation:Neuromuscular Research Group, Montreal, Neurological Institute, McGill University Montreal, Quebec H3A 2B4 1The Biotechnology Research Institute, National Research Council of Canada Montreal, Quebec H4P 2R2, Canada
Abstract:High titre (1011–1012 pfu/ml) suspensions of autonomouslyreplication-defective type 5 human adenovirus (AV) recombinantswith different reporter gene inserts (CMV-Luciferase (Lux),CMV-ß-galactosidase (Lac Z), RSV-Lux and RSV-Lac Z)were injected Into intact quadrlceps muscles of 1–5 dayold (Group 1) or 35–45 day old (Group 2) normal mice,as well as regenerating adult mouse muscles (Group 3) and 35day old mdx muscles (Group 4). The expression of the reportergenes was quantitated 10 days and 2 months later. At 10 dayspostinjection all reporter gene expression was very high inthe neonatally injected (Group 1) muscles. In Group 2 musclesthe transduction was markedly less. In Group 3 muscles the geneexpression was significantly better than in the Group 2 muscles.In adult mdx muscles (Group 4) where spontaneous regenerationis usually present, the results were similar to those in Group3 animals. At 2 months post-injection in Group 1 animals, theRSV-Lux expression was even higher than at 10 days postinjection.The cell surface density of
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