O - Alkyl derivatives of dioleoylphosphatidylcholine (DOPC) have been previously described as effective DNA transfection reagents. This communication reports the effects of the neutral helper lipid dioleoylphosphatidylethanolamine (DOPE) on the efficiency of transfection of BHK cells mediated by the O-ethyl-, O-hexyl-, and O-octadecyl- DOPC derivatives, compounds that by themselves are known to exhibit lyotropic phase preferences of lamellar, lamellar or cubic (depending on conditions) and inverse hexagonal, respectively. The effect of DOPE on transfection efficiency was found to be inhibition of the ethyl compound, stimulation or inhibition (depending on amount of DOPE) of the hexyl compound and stimulation in the case of the octadecyl compound, i.e., DOPE had a beneficial effect on the lipids that formed non-lamellar phases. X-ray diffraction was used to determine the lyotropic phase of the lipid-DOPE mixtures and of the lipid-DNA complex. DNA-lipid complexes tended to be lamellar unless the lipids had a very strong tendency toward the hexagonal phase, in which case the DNA complex was also hexagonal. Thus, a mixture of equal amounts of DOPE and hexyl-DOPC formed a lamellar complex with DNA, although the lipids on their own assumed the hexagonal phase. Octadecyl-DOPC formed a hexagonal phase with DOPE and the 1:1 DOPE mixture formed a hexagonal phase DNA complex; however, if smaller amounts of DOPE were included, the complex had a lamellar structure, in contrast to the hexagonal phase of the lipids by themselves. For these cationic phospholipids, there was not necessarily a benefit to transfection of generating a hexagonal phase lipid-DNA complex.
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