Pharmacokinetics of gene delivery in cells

Abstract

Since the first report, in the 1980s, of gene delivery with a cationic liposome, numerous attempts have been made to improve non-viral gene vectors. It has gradually become clear that transgene expression can be interrupted by several intracellular barriers (Fig. 1). The cellular association of naked DNA molecules is very poor, since negative charges on both the cell surface and the DNA molecules interrupt contact with each other via electrostatic interactions. Thus, in order to enhance cellular association, DNA was condensed with cationic polymers (Oupicky et al. 2000; Brown et al. 2001) and cationic liposomes (Li et al. 1999; Tranchant et al. 2004) that neutralize the effect of the negative charge. A cationic vector enhances cell-surface binding through interactions with the negative constituents of the cell surface (e.g. heparan sulfate proteoglycans) or through selective binding to specific receptors, resulting in a strong transgene expression. This method of condensation also enables targeting of the cells by modulating different ligands to the surfaces of the gene vectors (Table 1).