Abstract
A large variety of membrane-modifying agents have been used for the enhancement of DNA(lipo)polycation complex based gene transfer. The magnitude of improvement depends on the nature of the membrane-modifying agent and the (poly)cationic carrier. Within the lipid-free polymer-based systems (polyfection), ligand-polylysine mediated gene transfer can be improved up to more than 1000-fold by pH-specific endosomolytic peptides, glycerol, bacterial proteins or adenovirus particles. Ligand–polyethylenimine or dendrimer-based systems with per se higher efficiency are only slightly (about ten-fold) enhanced by endosomolytic agents. Membrane-active agents show only minor effects when applied to cationic lipid-based gene transfer (lipofection) with DNA complexes formed under optimized conditions using an three- to four-fold excess of positive charges. Less positively charged lipofection complexes can be strongly improved by the addition of membrane-active peptides.
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