After the physicochemical characterization of the polyplexes, the transfection capacity of the various OM-pBAE formulations was explored in HeLa cells. To our surprise, we found that the transfection was heavily influenced by the position of histidine within the single chain of endcapping heteromeric oligopeptide. Placing the histidine between the two arginines resulted in no significant difference in transfection with respect to the -CRRR + -CHHH OM-pBAE control. By contrast, pBAE-CRRH displayed a 20% decrease in transfection efficiency and, for the pBAE-CHRR formulation, transfection decreased up to 50% (Figure ). This effect of histidine position on the transfection capacity might be attributed to the influence of arginines on the protonation state of histidine, which may impact on the interaction of OM-pBAEs with the genetic material and the cell membrane, as well as the proton sponge effect that mediates its endosomal escape. Incorporation of a zwitterionic peptide to pBAEs-CRHR (pBAE-