ABSTRACT

The mainstay in the field of gene delivery has been the use of cationic lipids to complex and condense plasmid. Poly-L-lysine (PLL) has also attracted much attention, but PLL has several undesirable properties including polymer heterogeneity, toxicity, and potential immunogenicity. Although cationic lipids and PLL provide some beneficial properties for the delivery of plasmids, these carriers are far from the ideal carrier (see Table 1). For example, cationic lipids have been shown to induce the production of endogenous cytokines and act as adjuvants (Gregoriadis et al., 1997; Fortin and Therien, 1993; Gregoriadis, 1994a; Gregoriadis, 1994b). These effects may be tolerated or even beneficial for delivery of nucleic acid-based vaccines, but for therapeutic applications involving more frequent administration, these effects may make these carrier systems not very well tolerated. Further, the interactions of cationic lipids and plasmids are not very well understood. Complexation is often irreproducible and unstable, perhaps due to the heterogeneity of the complexes formed.