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.