Effects of membrane-active agents in gene delivery.
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.
Wagner
E
E
Institute of Biochemistry, Vienna University Biocentre, Austria. WagnerE@bender.co.at
D008566:Membranes / Q000187:drug effects*; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology; D011094:Polyethyleneimine / Q000737:chemistry; D014162:Transfection
D010455:Peptides; D011094:Polyethyleneimine