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Content Provider | World Health Organization (WHO)-Global Index Medicus |
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Author | Kochanek, S. Kelly, R. Clemens, P. R. Mack, L. M. Ontell, M. Chen, H. H. |
Description | Author Affiliation: Chen HH ( Department of Neurology, University of Pittsburgh, PA 15213, USA.); |
Abstract | Genetic correction of inherited muscle diseases, such as Duchenne muscular dystrophy, will require long term expression of the recombinant protein following gene transfer. We have shown previously that a new adenoviral vector that lacks all viral genes expressed both full-length dystrophin and beta-galactosidase in mdx (dystrophin-deficient) mouse muscle. We observed a significant histologic improvement of vector-transduced mdx muscle before the eventual loss of vector-encoded transgene expression. In this study, we investigated whether an immunological response against vector-encoded beta-galactosidase contributed to the loss of vector expression and affected vector persistence in muscle. Intramuscular vector injection in control normal mice resulted in an early and complete loss of beta-galactosidase expression accompanied by predominantly CD4+ and CD8+ lymphocytic infiltration and a significant loss of vector DNA. In contrast, intramuscular vector injection in lacZ transgenic mice resulted in persistent expression of beta-galactosidase for at least 84 days with no evidence of inflammation or significant loss of vector DNA. Our studies demonstrate that, in the absence of an immune response induced by beta-galactosidase expression, an adenoviral vector lacking all viral genes is stably maintained in muscle. |
ISSN | 00278424 |
e-ISSN | 10916490 |
Journal | Proceedings of the National Academy of Sciences of the United States of America |
Issue Number | 5 |
Volume Number | 94 |
Language | English |
Publisher | National Academy of Sciences |
Publisher Date | 1997-04-01 |
Publisher Place | United States |
Access Restriction | Open |
Subject Keyword | Adenoviridae Genetics Gene Transfer Techniques Genes, Viral Genetic Vectors Muscular Dystrophy, Animal T-Lymphocytes Immunology Metabolism Animals DNA, Viral Dystrophin Gene Dosage Gene Expression Regulation Genetic Therapy Injections, Intramuscular Mice Mice, Transgenic Muscle, Skeletal Therapy Transgenes Beta-Galactosidase Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. Multidisciplinary |
Content Type | Text |
Resource Type | Article |
Subject | Multidisciplinary |
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