Highly efficient transduction of endothelial cells by targeted artificial virus-like particles

Targeting the tumor vasculature by gene therapy is a potential ly powerful approach, but suitable vectors have not yet been described. We have designe d a new type of liposomal vector, based on the composition of anionic retro viral envelopes, that is serum-resistant and nontoxic. These artificial vir us-like envelopes (AVEs) were endowed with a cyclic RGD-containing peptide as a targeting device for the a(v)beta (3)-integrin on tumor endothelial ce lls (ECs). The packaging of plasmid DNA complexed with low-molecular-weight , nonlinear polyethyleneimine into these AVEs yielded artificial virus-like particles (AVPs) that transduced ECs with efficiencies of up to 99%. In co ntrast, transduction of a variety of other cell types by these RGD-AVPs was comparably inefficient under the same experimental conditions. This EC sel ectivity was mediated, in part, but not exclusively, by the RGD ligand, as suggested by the reduced, but still relatively high, transduction efficienc y seen with AVPs lacking RGD. The interaction of anionic lipids of the AVPs with ECs may therefore contribute to the observed selective and highly eff icient transduction of th is cell type. These findings suggest that the tar geted AVE technology is a useful approach to create highly efficient nonvir al vectors.