Co-polymer of histidine and lysine markedly enhances transfection efficiency of liposomes

Development of nonviral delivery systems is progressing toward a transfecti on efficiency sufficient to affect metabolic and neoplastic diseases in hum ans. Nevertheless, inadequate transfection efficiency of target cells with current nonviral systems still limits the utility of this therapy. In the c urrent study, we have determined that a co-polymer of histidine and lysine (H-K) enhances the transfection efficiency of liposomes, a leading nonviral system. We found that in the absence of serum, the addition of this polyme r increased transfection as much as 10-fold in comparison with the lipo- so me:DNA complex alone. More impressively, the co-polymer in the presence of serum increased transfection efficiency up to 100-fold. Furthermore, in viv o expression of luciferase in a tumor increased 15-fold with the addition o f H-K polymer to the liposome:plasmid DNA complexes. Without liposomes, the H-K polymer had little to no effect on transfection efficiency. We anticip ate that further modifications of this co-polymer will yield molecules with both increased complexity and transfection efficiency.