Abstract
A variety of membrane-modifying agents including pH-specific fusogenic or lytic peptides, bacterial proteins, lipids, glycerol, or inactivated virus particles have been evaluated for the enhancement of DNA–polycation complex-based gene transfer. The enhancement depends on the characteristics of both the cationic carrier for DNA and the membrane-modifying agent. Peptides derived from viral sequences such as the N-terminus of influenza virus haemagglutinin HA-2, the N-terminus of rhinovirus HRV2 VP-1 protein, and other synthetic or natural sequences such as the amphipathic peptides GALA, KALA, EGLA, JTS1, or gramicidin S have been tested. Ligand–polylysine-mediated gene transfer can be improved up to more than 1000-fold by membrane-active compounds. Other polycations like dendrimers or polyethylenimines as well as several cationic lipids provide a high transfection efficiency per se. Systems based on these polymers or lipids are only slightly enhanced by endosomolytic peptides or adenoviruses. Electroneutral cationic lipid–DNA complexes however can be strongly improved by the addition of membrane-active peptides.
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