POLYLYSINE-BASED TRANSFECTION SYSTEMS UTILIZING RECEPTOR-MEDIATED DELIVERY

Receptor-mediated gene transfer is a promising gene delivery technique . It employs a DNA-binding polycation, such as polylysine, to compact plasmid DNA to a size that can be taken up by cells (<100-200 nm). To allow internalization by receptor-mediated endocytosis, cell binding l igands, such as asialoglycoproteins or galactose for hepatocytes, anti -CD3 and anti-CDS for T-cells, and transferrin, have been covalently a ttached to polylysine. Intracellular barriers for successful gene tran sfer include release of DNA complexes from endosomes or lysosomes, nuc lear import of DNA complexes, and disassembly of the DNA-polylysine pa rticles. Release of particles from internal vesicles has been achieved by the addition of lysosomotropic agents or glycerol to the transfect ion medium, or by the incorporation of endosomolytic compounds, such a s viruses or membrane active peptides. This technique has already been used to transfect certain organs in vivo, including liver and lung. ( C) 1998 Elsevier Science B.V.