NONVIRAL GENE DELIVERY - VEHICLE AND DELIVERY CHARACTERIZATION

The development of non-viral gene therapy has been hampered by an inab ility to reproducibly manufacture and characterize delivery system com ponents and final formulations. Formation of interpolyelectrolyte comp lexes as the basis of various gene delivery methods has been approache d as the first step towards development of synthetic viruses. We have found that preparation of interpolyelectrolyte complexes from disperse reagents gives a more homogeneous gene delivery vehicle than other me thods. Methods which increase homogeneity also result in higher transf ection efficiency in vivo. Expression levels of human growth hormone a nd other reporter proteins in mice confirm the potential of parenteral non-viral gene delivery for some therapeutic applications. Serum is d emonstrated to inhibit transfection efficiency in vivo. Our results su ggest that further development of methods to manufacture homogeneous d isperse non-viral delivery vehicles with stealth characteristics may e nhance both the potency and reproducibility of gene transfer in vivo.