Helper-mediated transfection

We like to emphasize here, that the efficiency of a helper lipid like DOPE is, however, influenced by the packing of the alkyl tails in the membrane formed by the cationic carrier amphiphile. This was demonstrated by a comparative study of two structurally related bilayer-forming surfactants, SAINT-2 (with two C18 l tails) and SAINT-5 (with two C18 0 tails) (Figure 16.10). Both carriers display transfection activity, but DOPE exerts a positive effect on SAINT-2-mediated transfection, but has a negligible effect on transfection mediated by SAINT-5. Interestingly, DOPE effectively enhances DNA dissociation from the lipoplexes formed from both carriers. Most likely, membrane stiffness plays an important role here. Since the bilayer composed of SAINT-5 is more rigid than that formed from SAINT-2, because of the absence of unsaturation in the tails, the plasmid DNA becomes less effectively condensed, and the lipoplex is structurally deformed. This has no effect on cellular uptake but reduces the efficiency of translocation of the plasmid across the membranes of the endosome and/or of the cell nucleus. 

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