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New strategy for transfection: mixtures of medium-chain and long-chain cationic lipids synergistically enhance transfection

Abstract

To date, the primary approach to improve the transfection properties of cationic lipids has been the synthesis of new kinds of cationic amphipaths or the inclusion of noncationic helper lipids. Here, it is reported that an alternative approach can be unusually effective, namely, the combination of two cationic lipid derivatives having the same head group but tails of different chain lengths. Particularly efficient was the combination of dilauroyl (12 carbon chain) and dioleoyl (18 carbon chain) homologues of O-ethylphosphatidylcholine. This mixture transfected DNA into human umbilical artery endothelial cells (HUAEC) more than 30-fold more efficiently than either compound separately. A unique advantage of this kind of combination agent is that transfection can be optimized either in the presence or absence of serum by adjusting the component ratio.

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Acknowledgements

We thank Yaeko Hiyama (Northwestern University, USA) for synthesizing some of the compounds used in investigating the lipid mixture effects. This study is supported by NIH Grant GM52329.

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The term ‘lipoid’ is more accurate since ‘lipid’ refers to natural products, whereas ‘lipoid’ is used to molecules that are similar to lipids in structure and in properties but not natural products.

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Wang, L., MacDonald, R. New strategy for transfection: mixtures of medium-chain and long-chain cationic lipids synergistically enhance transfection. Gene Ther 11, 1358–1362 (2004). https://doi.org/10.1038/sj.gt.3302297

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