Gao H, Hui K M
Gene Vector Laboratory, Division of Cellular and Molecular Research, National Cancer Center, 11 Hospital Drive, Singapore 169610.
Gene Ther. 2001 Jun;8(11):855-63. doi: 10.1038/sj.gt.3301471.
The synthesis of a series of novel cationic lipids through the systematic substitution of cholesterol derivatives that could greatly enhance the delivery and expression of plasmid DNA in vitro and in vivo is described. Two of the newly synthesized lipids, designated as NCC4 and NCC10, were chosen to be studied in detail and gave much higher levels of gene expression than that which could be obtained with some of the conventional cationic polymers and cationic liposomes. In vivo studies with both NCC4 and NCC10 also showed better ability in delivering the reporter gene to the target cells through intrasplenic injection. In addition, by varying the DNA/lipid charge ratios, NCC4 and NCC10 can withstand serum inactivation in vitro. However, this does not correlate with the corresponding increase in the level of gene expression following systemic gene delivery with NCC4 and NCC10 in vivo.
本文描述了通过对胆固醇衍生物进行系统取代来合成一系列新型阳离子脂质的方法，这些脂质能够在体外和体内极大地增强质粒DNA的递送和表达。新合成的两种脂质，命名为NCC4和NCC10，被挑选出来进行详细研究，它们的基因表达水平比一些传统阳离子聚合物和阳离子脂质体所能达到的水平高得多。对NCC4和NCC10进行的体内研究还表明，通过脾内注射，它们在将报告基因递送至靶细胞方面具有更好的能力。此外，通过改变DNA/脂质电荷比，NCC4和NCC10在体外能够耐受血清灭活。然而，这与在体内用NCC4和NCC10进行全身基因递送后基因表达水平的相应增加并无关联。
