Intraluminal water increases expression of plasmid DNA in rat lung

Teiji Sawa, Hiroshi Miyazaki, Jean Francois Pittet, Jonathan Widdicombe, Michael A. Gropper, Satoru Hashimoto, Douglas J. Conrad, Hans G. Folkesson, Robert Debs, John R. Forsayeth, Bryan Fox, Jeanine P. Wiener-Kronish

Research output: Contribution to journalArticle

27 Scopus citations

Abstract

Effective gene delivery to specific organs is a major goal for human gene therapy. The lung's structure allows instillation of agents into the airspaces, directly adjacent to the lung epithelium. We hypothesized that the airspace instillation of hypotonic solutions would increase the permeability of the lung epithelium and increase DNA uptake. This hypothesis was tested by instilling plasmid DNA (p4241) encoding the luciferase gene in isotonic and hypotonic solutions. The highest luciferase expression in the lung was achieved after the instillation of this plasmid DNA in distilled water. Aerosolization of water just before the instillation of the plasmid DNA also enhanced the expression level of luciferase in the lung. In addition, an intralobar instillation of the plasmid DNA in water significantly increased the luciferase expression, suggesting that the instillation of the plasmid over a smaller surface area increased expression. Levels of expression could be measured for 3 days. Water increases the permeability of lung epithelial cells transiently and/or enhances genre expression and can be used to achieve gene expression in the lung airspaces for short intervals without toxicity.

Original languageEnglish (US)
Pages (from-to)933-941
Number of pages9
JournalHuman Gene Therapy
Volume7
Issue number8
StatePublished - May 20 1996
Externally publishedYes

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ASJC Scopus subject areas

  • Genetics

Cite this

Sawa, T., Miyazaki, H., Pittet, J. F., Widdicombe, J., Gropper, M. A., Hashimoto, S., Conrad, D. J., Folkesson, H. G., Debs, R., Forsayeth, J. R., Fox, B., & Wiener-Kronish, J. P. (1996). Intraluminal water increases expression of plasmid DNA in rat lung. Human Gene Therapy, 7(8), 933-941.