Polyethylenimine-based intravenous delivery of transgenes to mouse lung

D. Goula, C. Benoist, S. Mantero, G. Merlo, G. Levi, B. A. Demeneix

Research output: Contribution to journalArticle

Abstract

Generally, cationic vector-based intravenous delivery of DNA is hindered by interactions of positively charged complexes with serum proteins. However, if optimally formulated, cationic vectors can provide reasonable levels of transfection in the lung either by intravenous or intrapulmonary routes. We investigated the in vivo transfection capacity of a cationic polymer: linear, 22 kDa polyethylenimine. PEI/DNA complexes were formulated in 5% glucose and delivered into adult mice through the tail vein. Two marker genes were used, β-galactosidase and luciferase. High levels of luciferase expression (107 RLU/mg protein) were found in the lung when DNA was complexed with PEI at a ratio of 4 nitrogen equivalents per DNA phosphate. Lower levels of transfection were found in the heart, spleen, liver and kidney. Expression was dose- and time-dependent in all tissues examined. In the lung, β-galactosidase staining showed transgene expression in clusters of 10 or more pulmonary cells including the alveolar endothelium, squamous and great alveolar epithelial cells (type I and II pneumocytes) and septal cells. These findings indicate that the complexes pass the capillary barrier in the lung. Although the delivery mechanism requires elucidation, linear PEI has promise as a vector for intravenous transfer of therapeutic genes.

Original languageEnglish
Pages (from-to)1291-1295
Number of pages5
JournalGene Therapy
Volume5
Issue number9
Publication statusPublished - 1998

Keywords

  • Cationic polymers
  • Gene therapy
  • Nonviral
  • Plasmid DNA
  • Pneumocytes

ASJC Scopus subject areas

  • Genetics

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    Goula, D., Benoist, C., Mantero, S., Merlo, G., Levi, G., & Demeneix, B. A. (1998). Polyethylenimine-based intravenous delivery of transgenes to mouse lung. Gene Therapy, 5(9), 1291-1295.