標題: Optimizing cationic and neutral lipids for efficient gene delivery at high serum content
作者: Chan, Chia-Ling
Ewert, Kai K.
Majzoub, Ramsey N.
Hwu, Yeu-Kuang
Liang, Keng S.
Leal, Cecilia
Safinya, Cyrus R.
電子物理學系
Department of Electrophysics
關鍵字: cationic liposomes;gene delivery;glycerol monooleate;multivalent cationic lipid;serum
公開日期: 1-Mar-2014
摘要: BackgroundCationic 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.
URI: http://dx.doi.org/10.1002/jgm.2762
http://hdl.handle.net/11536/24499
ISSN: 1099-498X
DOI: 10.1002/jgm.2762
期刊: JOURNAL OF GENE MEDICINE
Volume: 16
Issue: 3-4
起始頁: 84
結束頁: 96
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