Receptor-mediated delivery of plasmid DNA

A goal in gene therapy is the delivery of genes to the surface of the target cells, followed by an efficient uptake and transport across intracellular barriers into the nucleus of cells. Amongst other systems, DNA/polycation particles coated with cell-binding ("targeting") ligands such as transferrin, EGF, asialoglycoprotein receptor binding molecules, or various antibodies are being optimized for this purpose. To allow ionic binding to theDNA, in most cases ligands are covalently linked to the polycations polylysine or polyethylenimine (PEI). Ligand polylysine mediated gene transfer is strongly dependent on release from the endosomes and can be improved by pH-specific endosomolytic peptides or inactivated viral particles. In contrast, ligand PEI mediated gene transfer is far less dependent on the presence of endosomolytic agents. Coating of DNA complexes with polyethylenglycol (PEG) through covalent coupling to PEI strongly reduces plasma protein binding and stabilizes complexes in size (40-60 nm in diameter). Intravenous injection of PEG-modified complexes into tumor-bearing mice results in significant gene expression in the tumor.