NONVIRAL VECTORS FOR IN-VIVO GENE DELIVERY - PHYSICOCHEMICAL AND PHARMACOKINETIC CONSIDERATIONS

The use of nonviral vectors is an attractive in vivo gene delivery str ategy that is simpler than, and lacks some risks inherent in, viral sy stems. Liposomes and receptor-mediated polycation systems are promisin g carriers for delivery and expression of plasmid DNA encoding genes i nto the target cells. Many barriers need to be overcome for successful in vivo DNA delivery using these carrier systems. Such factors as ext ent of DNA condensation, particle size of the DNA complex, route of ad ministration, stability against nucleases, target sites, in vivo dispo sition, binding to cell surface receptor and internalization, and intr acellular trafficking affect in vivo gene delivery and expression. Thi s review will provide a critical discussion of the merits and limitati ons of liposomal and polycationic carrier systems for gene transfer fr om the viewpoints of their physicochemical and pharmacokinetic propert ies.