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来自超荷化卷曲螺旋蛋白与阳离子脂质杂化复合物的基因递送

Gene delivery from supercharged coiled-coil protein and cationic lipid hybrid complex.

作者信息

More Haresh T, Frezzo Joseph A, Dai Jisen, Yamano Seiichi, Montclare Jin K

机构信息

Department of Chemical and Biomolecular Engineering, New York University Polytechnic School of Engineering, 6 Metrotech Center, Brooklyn, NY 11201, USA.

Department of Prosthodontics, New York University College of Dentistry, New York, NY 10010, USA.

出版信息

Biomaterials. 2014 Aug;35(25):7188-93. doi: 10.1016/j.biomaterials.2014.05.005. Epub 2014 May 27.

Abstract

A lipoproteoplex comprised of an engineered supercharged coiled-coil protein (CSP) bearing multiple arginines and the cationic lipid formulation FuGENE HD (FG) was developed for effective condensation and delivery of nucleic acids. The CSP was able to maintain helical structure and self-assembly properties while exhibiting binding to plasmid DNA. The ternary CSP·DNA(8:1)·FG lipoproteoplex complex demonstrated enhanced transfection of β-galactosidase DNA into MC3T3-E1 mouse preosteoblasts. The lipoproteoplexes showed significant increases in transfection efficiency when compared to conventional FG and an mTat·FG lipopolyplex with a 6- and 2.5-fold increase in transfection, respectively. The CSP·DNA(8:1)·FG lipoproteoplex assembled into spherical particles with a net positive surface charge, enabling efficient gene delivery. These results support the application of lipoproteoplexes with protein engineered CSP for non-viral gene delivery.

摘要

一种由带有多个精氨酸的工程化带正电卷曲螺旋蛋白(CSP)和阳离子脂质制剂FuGENE HD(FG)组成的脂蛋白复合物被开发用于核酸的有效浓缩和递送。CSP能够保持螺旋结构和自组装特性,同时表现出与质粒DNA的结合。三元CSP·DNA(8:1)·FG脂蛋白复合物在将β-半乳糖苷酶DNA转染到MC3T3-E1小鼠前成骨细胞中时表现出增强的转染效果。与传统的FG和mTat·FG脂质多聚体相比,脂蛋白复合物的转染效率显著提高,分别提高了6倍和2.5倍。CSP·DNA(8:1)·FG脂蛋白复合物组装成具有净正表面电荷的球形颗粒,能够实现高效的基因递送。这些结果支持了具有蛋白工程化CSP的脂蛋白复合物在非病毒基因递送中的应用。

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