Cholesterol domains enhance transfection.
Cholesterol domains enhance transfection.
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DOI：
10.4155/tde.13.16
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发表时间：
2013-04
影响因子：
4.2
通讯作者：
Anchordoquy TJ
中科院分区：
文献类型：
--
作者：
Betker JL;Kullberg M;Gomez J;Anchordoquy TJ
脂质复合物中胆固醇结构域的形成与细胞培养物和体内的血清稳定性和转染率的提高有关。本研究利用饱和磷脂酰胆碱的能力，以促进形成的胆固醇结构域在低得多的胆固醇含量比以前的工作中使用。结果表明，具有相同的胆固醇和阳离子脂质含量的脂质复合物表现出显着提高的转染效率时，域是存在的，与以前的工作一致。此外，在不存在血清的情况下评估转染率的研究表明，结构域增强转染的能力不依赖于与血清蛋白的相互作用。与该假设一致，组成这些lipoplex制剂的冠的吸附蛋白的表征没有揭示转染与特定蛋白的吸附之间的相关性。最后，我们表明，与血清蛋白的相互作用，可以促进域的形成，在某些配方，从而导致增强转染后，血清暴露。
The formation of cholesterol domains in lipoplexes has been associated with enhanced serum stability and transfection rates both in cell culture and in vivo. This study utilizes the ability of saturated phosphatidylcholines to promote the formation of cholesterol domains at much lower cholesterol contents than have been utilized in previous work. The results show that lipoplexes with identical cholesterol and cationic lipid contents exhibit significantly improved transfection efficiencies when a domain is present, consistent with previous work. In addition, studies assessing transfection rates in the absence of serum demonstrate that the ability of domains to enhance transfection is not dependent on interactions with serum proteins. Consistent with this hypothesis, characterization of the adsorbed proteins composing the corona of these lipoplex formulations did not reveal a correlation between transfection and the adsorption of a specific protein. Finally, we show that the interaction with serum proteins can promote domain formation in some formulations, and thereby result in enhanced transfection only after serum exposure.