肝靶向基因给药系统AsOR-PL+PEG-PEI的研究  

Multi-component DNA delivery system targeted for hepatocyte-AsOR-PL/ PEG-PEI

作　　者：靳雪源[1] 张玲霞[1] 楼敏[1] 谢建芳[1] 

机构地区：[1]中国人民解放军第302医院感染五科,北京市100039

出　　处：《世界华人消化杂志》2002年第3期295-298,共4页World Chinese Journal of Digestology

摘　　要：目的:研制含有靶向配基、DNA聚合亚基、溶酶体活性成分及聚乙二醇等多种组分的肝靶向的DNA给药系统。 方法:分别制备AsOR-PL偶合物及PEG-PEI偶合物,然后按照不同的比例先后与报告基因DNA形成复合物,再进行Huh-7细胞的体外转染试验和静脉给药后小鼠体内的表达试验。 结果:AsOR-PL/PEG-PEI/DNA复合物对受体阳性的Huh-7细胞具有较高的转染效率;小鼠尾静脉给药后能够在肝脏特异性表达。 结论:含有靶向配基、DNA聚合亚基、溶酶体活性成分及聚乙二醇等多种组分的载体系统能将DNA选择性的投放于小鼠肝脏,显示了较好的应用前景。AIM: To develop a multi-component DNA delivery system which incorporated hepatocyte targeting ligand, DNA compressing domain and endosome disruptive molecule in one complex.METHODS:AsOR was conjugated to PL by EDC; The active ester of PEG derivative was reacted with the amino groups in PEI to form PEG-PEI conjugate; DNA was first complexed with PEG-PEI and then with AsOR-PL. In vitro transfection experiment was conducted in the galactose receptor positive Huh-7 cells. In vivo transduction was also evaluated in mice after tail vein injection.RESULTS: AsOR-PL/ PEG-PEI/ DNA was able to effectively deliver luciferase gene into the galactose receptor positive Huh-7 cells in vitro. The transfection was specifically inhibited by the synthesized ligand-lactosaminated BSA. After tail vein injection, the reporter gene was expressed specifically in the liver of mice.CONCLUSION: The multi-component system of AsOR-PL and PEG-PEI can be used as a specific and efficient DNA carrier.

关 键 词：肝靶向基因给药系统 AsOR-PL+PEG-PEI 研究 肝肿瘤 

分 类 号：R346[医药卫生—基础医学]