NDLI: An improved helper-dependent adenoviral vector allows persistent gene expression after intramuscular delivery and overcomes preexisting immunity to adenovirus.

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An improved helper-dependent adenoviral vector allows persistent gene expression after intramuscular delivery and overcomes preexisting immunity to adenovirus.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Maione, D. Liberatoscioli, L. La Monica, N. Sandig, V. Franlin, L. L. Ciliberto, G. Della Rocca, C. Giannetti, P. Savino, R. D'arrigo, R.
Description	Author Affiliation: Maione D ( Istituto di Ricerche di Biologia Molecolare P. Angeletti, 00040 Pomezia, Rome, Italy.);
Abstract	Helper-dependent adenoviral vectors deleted of all viral coding sequences have shown an excellent gene expression profile in a variety of animal models, as well as a reduced toxicity after systemic delivery. What is still unclear is whether long-term expression and therapeutic dosages of these vectors can be obtained also in the presence of a preexisting immunity to adenovirus, a condition found in a high proportion of the adult human population. In this study we performed intramuscular delivery of helper-dependent vectors carrying mouse erythropoietin as a marker transgene. We found that low doses of helper-dependent adenoviral vectors can direct long-lasting gene expression in the muscles of fully immunocompetent mice. The best performance-i.e., 100% of treated animals showing sustained expression after 4 months-was achieved with the latest generation helper-dependent backbones, which replicate and package at high efficiency during vector propagation. Moreover, efficient and prolonged transgene expression after intramuscular injection was observed with limited vector load also in animals previously immunized against the same adenovirus serotype. These data suggest that human gene therapy by intramuscular delivery of helper-dependent adenoviral vectors is feasible.
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	11
Volume Number	98
Language	English
Publisher	National Academy of Sciences
Publisher Date	2001-05-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Adenoviruses, Human Immunology Genetic Vectors Helper Viruses Animals Erythropoietin Genetics Gene Expression Gene Transfer Techniques HeLa Cells Injections, Intramuscular Mice Mice, Inbred BALB C Mice, Inbred C57BL Multidisciplinary
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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