mediated gene delivery in the mouse.+

+To the memory of Demetrios Papahadjopoulos. Background: Several nonviral vectors including L-PEI confer a pronounced lung tropism to plasmid DNA when injected in the mouse tail vein in a non-ionic solution. Methods and Results: We have optimized this route by injecting 50 µg DNA with excess L-PEI (N/P=10) in a large volume of 5 % glucose (0.4 ml). In these conditions, 1-5 % percent of lung cells were transfected (corresponding to 2 ng luciferase/mg protein), the other organs remaining essentially refractory to transfection (1-10 pg luciferase/mg protein). Beta-galactosidase histochemistry confirmed alveolar cells, including pneumocytes, to be the main target, thus leading to the puzzling observation that the lung microvasculature must be permeable to cationic L-PEI/DNA particles of ca. 60 nm. A smaller injected volume, premixing of the complexes with autologous mouse serum, as well as removal of excess free L-PEI, all severely decreased transgene expression in the lung. Arterial or portal vein delivery did not increase transgene expression in other organs