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首页> 外文期刊>Journal of Medicinal Chemistry >Novel series of non-glycerol-based cationic transfection lipids for use in liposomal gene delivery.
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Novel series of non-glycerol-based cationic transfection lipids for use in liposomal gene delivery.

机译:新型系列的非甘油基阳离子转染脂质,用于脂质体基因递送。

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摘要

A novel series of nontoxic and non-glycerol-based simple monocationic transfection lipids containing one or two hydroxyethyl groups directly linked to the positively charged nitrogen atom were synthesized. The in vitro transfection efficiencies of these new liposomal gene delivery reagents were better than that of lipofectamine, a widely used transfection agent in cationic lipid-mediated gene transfer. The most efficient transfection formulation was observed to be a 1:1:0.3 mol ratio of DHDEAB (N, N-di-n-hexadecyl-N,N-dihydroxyethylammonium bromide):cholesterol:HDEAB (N-n-hexadecyl-N,N-dihydroxyethylammonium bromide) using a DHDEAB-to-DNA charge ratio (+/-) of 0.3:1. Observation of good transfection at charge ratios lower than 1 suggests that the amphiphile-DNA complex may have net negative charge. Our results reemphasize the important point that in cationic lipid-mediated gene delivery, the overall charge of the lipid-DNA complex need not always be positive. In addition, our transfection results also imply that favorable hydrogen-bonding interactions between the lipid headgroups and the cell surface of biological membranes may have some role for improving the transfection efficiency in cationic lipid-mediated gene delivery.
机译:合成了一系列新的无毒且基于非甘油的简单单阳离子转染脂质,这些脂质包含一个或两个直接与带正电的氮原子连接的羟乙基。这些新型脂质体基因递送试剂的体外转染效率优于脂质转染剂lipofectamine,后者是阳离子脂质介导的基因转移中广泛使用的转染剂。观察到最有效的转染制剂是DHDEAB(N,N-二-正十六烷基-N,N-二羟乙基溴化铵):胆固醇:HDEAB(Nn-十六烷基-N,N- DHDEAB与DNA的电荷比(+/-)为0.3:1。以低于1的电荷比观察到良好的转染,表明两亲DNA复合物可能具有净负电荷。我们的结果再次强调了重要的一点,即在阳离子脂质介导的基因传递中,脂质-DNA复合物的总电荷不一定总是正的。此外,我们的转染结果还暗示脂质头基与生物膜细胞表面之间的良好氢键相互作用可能对提高阳离子脂质介导的基因传递的转染效率具有一定作用。

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