Polycation Structure Mediates Expression of Lyophilized Polycation/pDNA Complexes

Lyophilization of polycation/pDNA complexes provides stable, long-term storage of complexes prior to clinical use but also reduces gene delivery efficiency. We examined whether polycation structure mediates effects of lyophilization on gene expression. Linear and branched PEI of the same molecular weight were used as a model system. Interestingly, pDNA/linear PEI complexes led to much smaller effects on gene expression following lyophilization compared with branched PEI complexes. The effect of polycation structure correlated with changes in dissociation ability of pDNA/PEI complexes. These results will be useful for developing new gene delivery vehicles.Polyethyleneimine/plasmid DNA complexes can be lyophilized for stable storage prior to use. Lyophilization leads to reduction in gene expression efficacy of complexes compared with freshly prepared complexes, but the degree of this reduction can be controlled through PEI architecture. This effect correlates with the degree of dissociation observed following exposure to heparin.