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dc.contributor.authorChan, Chia-Lingen_US
dc.contributor.authorEwert, Kai K.en_US
dc.contributor.authorMajzoub, Ramsey N.en_US
dc.contributor.authorHwu, Yeu-Kuangen_US
dc.contributor.authorLiang, Keng S.en_US
dc.contributor.authorLeal, Ceciliaen_US
dc.contributor.authorSafinya, Cyrus R.en_US
dc.description.abstractBackgroundCationic liposome (CL)-DNA complexes are promising gene delivery vectors with potential application in gene therapy. A key challenge in creating CL-DNA complexes for application is that their transfection efficiency (TE) is adversely affected by serum. In particular, little is known about the effects of a high serum content on TE, even though this may provide design guidelines for application in vivo. MethodsWe prepared CL-DNA complexes in which we varied the neutral lipid [1,2-dioleoyl-sn-glycerophosphatidylcholine, glycerol-monooleate (GMO), cholesterol], the headgroup charge and chemical structure of the cationic lipid, and the ratio of neutral to cationic lipid; we then measured the TE of these complexes as a function of serum content and assessed their cytotoxicity. We tested selected formulations in two human cancer cell lines (M21/melanoma and PC-3/prostate cancer). ResultsIn the absence of serum, all CL-DNA complexes of custom-synthesized multivalent lipids show high TE. Certain combinations of multivalent lipids and neutral lipids, such as MVL5(5+)/GMO-DNA complexes or complexes based on the dendritic-headgroup lipid TMVLG3(8+) exhibited high TE both in the absence and presence of serum. Although their TE still dropped to a small extent in the presence of serum, it reached or surpassed that of benchmark commercial transfection reagents, particularly at a high serum content. ConclusionsTwo-component vectors (one multivalent cationic lipid and one neutral lipid) can rival or surpass benchmark reagents at low and high serum contents (up to 50%, v/v). We propose guidelines for optimizing the serum resistance of CL-DNA complexes based on a given cationic lipid. Copyright (c) 2014 John Wiley & Sons, Ltd.en_US
dc.subjectcationic liposomesen_US
dc.subjectgene deliveryen_US
dc.subjectglycerol monooleateen_US
dc.subjectmultivalent cationic lipiden_US
dc.titleOptimizing cationic and neutral lipids for efficient gene delivery at high serum contenten_US
dc.identifier.journalJOURNAL OF GENE MEDICINEen_US
dc.contributor.departmentDepartment of Electrophysicsen_US
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