Rao N Madhusudhana, Gopal Vijaya
Centre for Cellular and Molecular Biology, Uppal Road, Hyderabad, 500 007, India.
Biosci Rep. 2006 Aug;26(4):301-24. doi: 10.1007/s10540-006-9026-8.
Cationic lipids are conceptually and methodologically simple tools to deliver nucleic acids into the cells. Strategies based on cationic lipids are viable alternatives to viral vectors and are becoming increasingly popular owing to their minimal toxicity. The first-generation cationic lipids were built around the quaternary nitrogen primarily for binding and condensing DNA. A large number of lipids with variations in the hydrophobic and hydrophilic region were generated with excellent transfection efficiencies in vitro. These cationic lipids had reduced efficiencies when tested for gene delivery in vivo. Efforts in the last decade delineated the cell biological basis of the cationic lipid gene delivery to a significant detail. The application of techniques such as small angle X-ray spectroscopy (SAXS) and fluorescence microscopy, helped in linking the physical properties of lipid:DNA complex (lipoplex) with its intracellular fate. This biological knowledge has been incorporated in the design of the second-generation cationic lipids. Lipid-peptide conjugates (peptoids) are effective strategies to overcome the various cellular barriers along with the lipoplex formulations methodologies. In this context, cationic lipid-mediated gene delivery is considerably benefited by the methodologies of liposome-mediated drug delivery. Lipid mediated gene delivery has an intrinsic advantage of being a biomimetic platform on which considerable variations could be built to develop efficient in vivo gene delivery protocols.
阳离子脂质在概念和方法上都是将核酸递送至细胞的简单工具。基于阳离子脂质的策略是病毒载体可行的替代方案，并且由于其极低的毒性而越来越受欢迎。第一代阳离子脂质主要围绕季铵氮构建，用于结合和凝聚DNA。大量在疏水和亲水区域具有不同结构的脂质在体外具有优异的转染效率。然而，当在体内进行基因递送测试时，这些阳离子脂质的效率有所降低。在过去十年中，人们对阳离子脂质基因递送的细胞生物学基础进行了深入研究。小角X射线光谱学（SAXS）和荧光显微镜等技术的应用，有助于将脂质：DNA复合物（脂质体）的物理性质与其细胞内命运联系起来。这些生物学知识已被纳入第二代阳离子脂质的设计中。脂质 - 肽缀合物（类肽）是克服各种细胞屏障以及脂质体配方方法的有效策略。在这种情况下，阳离子脂质介导的基因递送在很大程度上受益于脂质体介导的药物递送方法。脂质介导的基因递送具有作为仿生平台的固有优势，可以在此基础上进行大量的改进，以开发高效的体内基因递送方案。
