Please use this identifier to cite or link to this item:
|Title: ||Optimizing cationic and neutral lipids for efficient gene delivery at high serum content|
|Authors: ||Cyrus R Safinya|
Kai K. Ewert
Keng S. Liang
|Keywords: ||multivalent cationic lipid|
|Issue Date: ||2018-07-05T08:03:08Z
|Publisher: ||JOURNAL OF GENE MEDICINE|
|Abstract: ||Abstract: BACKGROUND:Cationic 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.
METHODS:We 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).
RESULTS:In 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.
CONCLUSIONS:Two-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.
|Relation: ||16(3-4) pp.84-96|
|Appears in Collections:||[光電科學研究所] 期刊論文|
Files in This Item:
All items in NTOUR are protected by copyright, with all rights reserved.