Structure and structure-activity correlations of cationic lipid/DNA complexes: supramolecular assembly and gene delivery
INTRODUCTION Following the initial publication of the papers by Felgner et al. (1987) and Huang et al. (1991), the entire field of gene therapy based on synthetic nonviral delivery systems has enjoyed a renaissance of sorts (Chesnoy and Huang, 2000; Nabel et al., 1993; Miller, 1998). In addition, other groups have demonstrated gene expression in vivo in targeted organs (Zhu et al., 1993; Anwer et al., 2000) and in human clinical trials (Nabel et al., 1993; Noone et al., 2000; Laitinen et al., 2000). Felgner etal. (1987) hypothesized that cationic liposomes (CLs), when mixed with DNA to form (CL/DNA) complexes with an overall positive charge, should lead to enhanced transfection compared to other synthetic vectors-such as cationic polymers and peptides-because of the enhanced stability and electrostatic interactions between cationic CL/DNA and anionic plasma membranes of mammalian cells. Compared to polymer and peptide-based delivery systems, cationic liposomes tend to mediate higher transfection in most cell lines studied to date.