Ren T, Zhang G, Song Y K, Liu D
Department of Pharmaceutical Science, School of Pharmacy, University of Pittsburgh, PA 15261, USA.
J Drug Target. 1999 Dec;7(4):285-92. doi: 10.3109/10611869909085511.
A new series of cationic lipids has been synthesized for gene delivery using 3,5-dihydroxybenzyl alcohol as the backbone and starting material. Using CMV driven expression system and luciferase gene as a reporter, we demonstrated that the transfection activity of these new lipids when formulated with Tween 80 as co-lipid is comparable to that of DOTAP, one of the most commonly used cationic lipids for transfection. Among the four different cell lines tested including murine melanoma BL-6 cells, human embryonic kidney 293 cells, HepG2 and HeLa cells, the highest transgene expression was seen in 293 cells. Results from in vivo experiments using mice as an animal model show that these cationic lipids preferentially transfect the cells in the lung upon tail vein administration. The cationic lipid, N,N,N-trimethyl-N-[3,5-bis(tetradecyloxy)benzyl] ammonium bromide 4c(di-C14:0) with two 14-hydrocarbon chains exhibits the best transfection activity. These results suggest that these new aromatic ring-based cationic lipids are useful transfection reagents for both in vitro and in vivo gene transfer studies.
已经合成了一系列新的阳离子脂质用于基因传递，该系列以3,5 - 二羟基苄醇作为主链和起始原料。使用巨细胞病毒（CMV）驱动的表达系统和荧光素酶基因作为报告基因，我们证明了这些新脂质与吐温80作为共脂质配制时的转染活性与DOTAP相当，DOTAP是最常用的用于转染的阳离子脂质之一。在所测试的四种不同细胞系中，包括小鼠黑色素瘤BL - 6细胞、人胚肾293细胞、HepG2和HeLa细胞，在293细胞中观察到最高的转基因表达。以小鼠作为动物模型的体内实验结果表明，这些阳离子脂质在尾静脉给药后优先转染肺部细胞。具有两条14 - 碳氢链的阳离子脂质N,N,N - 三甲基 - N - [3,5 - 双（十四烷氧基）苄基]溴化铵4c（二 - C14:0）表现出最佳的转染活性。这些结果表明，这些基于芳香环的新型阳离子脂质是用于体外和体内基因转移研究的有用转染试剂。
