A cationic lipid-based gene delivery system composed of N-[(1-(2,3-dioleylo
xy)propyl)]-N-N-N-trimethylammonium chloride and cholesterol, at a 4:1 mola
r ratio, was developed For systemic administration. Plasmid biodistribution
and expression were characterized in syngeneic mouse tumor model squamous
cell carcinoma VII cells. A reporter gene expression plasmid was used for b
iodistribution of plasmid and expression. The results showed that lungs and
primary tumors were transfected. Fluorescence microscopy showed that fluor
escent-labeled transfection complexes were passively targeted to the tumor
vasculature and that the endothelial cells internalized the plasmid. Transg
ene expression was characterized based on duration of expression and dosing
schedule. In vivo gene transfer with an interleukin-12 expression plasmid
yielded protein levels in blood, lungs, and primary tumor after intravenous
administration. Efficacy studies showed that 15 mu g of interleukin-12 pla
smid was sufficient to produce a gene-specific inhibition of primary tumor
growth. These results characterize the vascularity of the tumor model, char
acterize the in vivo gene transfer properties of the plasmid-based gene del
ivery system, and show that the transgene expression level was sufficient t
o elicit a biological response by inhibiting tumor growth.