Adenovirus encoding soluble tumor necrosis factor α receptor immunoglobulin prolongs gene expression of a cotransfected reporter gene in rat lung

Takashi Suda, Tsutomu Tagawa, Samer A. Kanaan, Benjamin D. Kozower, Niccolò Daddi, T. Mohanakumar, G. Alexander Patterson

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

Objective: Because almost all pulmonary diseases are not caused by one gene, multiple gene transfection is required for current gene therapy. Adenovirus is an important gene therapy vector, but a short duration and the inability of repeated administration remain limitations. The aims of this study were to evaluate whether adenoviral vector encoding soluble tumor necrosis factor a receptor immunoglobulin and β-galactosidase cotransfection prolongs gene expression and facilitates repeated vector administration to investigate the feasibility of a cotransfection strategy. Methods: F344 rats received intratracheal administration of 1 × 109 plaque-forming units of adenoviral vector encoding β-galactosidase or both adenoviral vector encoding β-galactosidase and adenoviral vector encoding soluble tumor necrosis factor α receptor immunoglobulin. In the expression study β-galactosidase gene expression in the lung was examined by means of enzyme-linked immunosorbent assay on days 2, 7, 14, 28, and 56 (n = 4/day). In the repeated transfection study, soluble tumor necrosis factor α receptor immunoglobulin and β-galactosidase were readministered once (7 days after the first adenovirus administration) or twice (on days 7 and 14; n = 4/day). A 2-way factorial analysis of variance was used for statistical analysis. Results: Soluble tumor necrosis factor α receptor immunoglobulin and β-galactosidase cotransfection prolonged the duration of β-galactosidase expression. However, antiadenovirus antibody production was significantly increased in the cotransfection group. In addition, there was no increase in β-galactosidase expression after readministration of soluble tumor necrosis factor α receptor immunoglobulin and β-galactosidase. Conclusion: Adenoviral vector encoding soluble tumor necrosis factor a receptor immunoglobulin and β-galactosidase cotransfection prolongs β-galactosidase expression but does not increase β-galactosidase expression after repeated administration. These results suggest that tumor necrosis factor a is one of the most important factors in regulating the duration of gene expression. The cotransfection approach is feasible, but the increase of antiadenovirus antibodies might make repeated cotransfection unfeasible.

Original languageEnglish
Pages (from-to)1155-1161
Number of pages7
JournalJournal of Thoracic and Cardiovascular Surgery
Volume126
Issue number4
DOIs
StatePublished - Oct 2003

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