Nonviral vectors for in vivo gene delivery: physicochemical and pharmacokinetic considerations

The use of nonviral vectors is an attractive in vivo gene delivery strategy that is simpler than, and lacks some risks inherent in, viral systems. Liposomes and receptor-mediated polycation systems are promising carriers for delivery and expression of plasmid DNA encoding genes into the target cells. Many barriers need to be overcome for successful in vivo DNA delivery using these carrier systems. Such factors as extent of DNA condensation, particle size of the DNA complex, route of administration, stability against nucleases, target sites, in vivo disposition, binding to cell surface receptor and internalization, and intracellular trafficking affect in vivo gene delivery and expression. This review will provide a critical discussion of the merits and limitations of liposomal and polycationic carrier systems for gene transfer from the viewpoints of their physicochemical and pharmacokinetic properties.