Synergism in gene delivery by small PEIs and three different nonviral vectors

We have reported earlier that a combination of low-molecular weight polyethylenimines (PEIs) with the cationic liposome, Dosper, results in a synergistic increase in the transfection efficiency. Now we have investigated whether this synergism is a general mechanism seen with other transfection reagents as well. Therefore, we have combined the low-molecular weight PEIs (MW 700 and 2000) with Dotap (a monocationic liposome), Lipofectamine (a combination of neutral and polycationic liposome), and Superfect (a dendrimer). The highest synergism was achieved with Lipofectamine and PEIs in the SMC cells, or with Dotap and PEIs in the C6 cells. Superfect did not induce any synergism. The combinations did not cause any changes in DNA condensing ability measured with ethidium bromide exclusions. The proton pump inhibitor, bafilomycin A1, had similar effects in both cell lines. Interestingly, the combination of Dosper (a positive control) and PEI caused the most effective transfection synergism in the presence of serum, although Lipofectamine, with or without PEIs, was a very potent reagent demonstrating the best transfection efficiency in the absence of serum. It is suggested that the PEI/Dosper-mediated synergism in the transfection efficiency may be a general mechanism for liposomal transfection reagents, although the effects can vary depending on cell lines.