Cationic liposome-DNA complexes: from liquid crystal science to gene delivery applications
Cationic liposome-DNA complexes: from liquid crystal science to gene delivery applications
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DOI：
10.1098/rsta.2006.1841
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发表时间：
2006-10-15
期刊：
影响因子：
5
通讯作者：
Samuel, Charles E.
中科院分区：
文献类型：
--
作者：
Safinya, Cyrus R.;Ewert, Kai;Samuel, Charles E.
目前，人们对DNA与带相反电荷的阳离子脂质体（CLs）混合组成的复合物的性质和结构产生了前所未有的兴趣。之所以引起人们的兴趣，是因为在世界范围的人类基因治疗临床试验中，这些复合物模仿天然病毒作为DNA的化学载体进入细胞。然而，由于我们对CL-DNA复合物与细胞相互作用的作用机制的理解仍然很差，在开发适合长期治疗应用的有效化学载体之前，需要有重要的额外见解和发现。最近的研究描述了同步x射线衍射，它揭示了CL-DNA复合物的液晶性质，以及三维激光扫描共聚焦显微镜，它揭示了CL-DNA的途径和与细胞的相互作用。这些现代技术的应用与功能转染效率测量相结合，揭示了液晶结构在生物功能中的重要性，表明基因从细胞质中复合物释放的机制取决于其精确的液晶性质和复合物的物理和化学参数（如膜电荷密度）。在5中，我们描述了一些最近的新结果，旨在开发用于基因传递的生物纳米管载体。
At present, there is an unprecedented level of interest in the properties and structures of complexes consisting of DNA mixed with oppositely charged cationic liposomes (CLs). The interest arises because the complexes mimic natural viruses as chemical carriers of DNA into cells in worldwide human gene therapy clinical trials. However, since our understanding of the mechanisms of action of CL-DNA complexes interacting with cells remains poor, significant additional insights and discoveries will be required before the development of efficient chemical carriers suitable for long-term therapeutic applications. Recent studies describe synchrotron X-ray diffraction, which has revealed the liquid crystalline nature of CL-DNA complexes, and three-dimensional laser-scanning confocal microscopy, which reveals CL-DNA pathways and interactions with cells. The importance of the liquid crystalline structures in biological function is revealed in the application of these modern techniques in combination with functional transfection efficiency measurements, which shows that the mechanism of gene release from complexes in the cell cytoplasm is dependent on their precise liquid crystalline nature and the physical and chemical parameters (for example, the membrane charge density) of the complexes. In 5, we describe some recent new results aimed at developing bionanotube vectors for gene delivery.