壳聚糖介导肝靶向性基因转导的体内实验研究

发布时间：2018-06-02 22:00

本文选题：肝靶向 + 纳米微囊　；参考：《第四军医大学》2005年硕士论文

【摘要】：基因治疗是现代医学研究的热点问题,以肝为靶点的基因治疗更是倍受关注。近年来,肝靶向性基因治疗取得了很大的进展。肝细胞是基因定向转导的理想靶部位,因为肝脏是人体少数几个实质细胞与血液直接相通的器官之一。而且肝窦状隙的内皮细胞基本上没有结缔组织,上面有许多大小不等的无隔膜的窗孔,小的直径约为0. μm,大的直径1μm。因此肝血管系统通透性较大,一些大分子物质可以自由通过,在血液和肝细胞之间没有严密的屏障结构。由于病毒载体安全性的局限,现阶段的基因治疗主要研究非病毒载体。传统的非病毒载体的转染效率较低。壳聚糖是一种新型的纳米微囊载体,具有生物可降解性和生物相容性,安全性较高且有较高的转染效率。以往的研究表明,壳聚糖在体外有较高的转染效率,小鼠体内实验证明壳聚糖在体内的转染效率也很高,而对于壳聚糖在大型动物体内的基因转导,国际上尚无文献报道。本实验选用半乳糖基化壳聚糖(GC),GC分子上带有半乳糖配体,可以与肝细胞表面特有的去唾液酸糖蛋白受体(ASGP—R)结合,从而实现肝靶向性基因转导。
[Abstract]:Gene therapy is a hot topic in modern medicine. In recent years, liver targeting gene therapy has made great progress. Hepatocytes are ideal targets for gene directed transduction because the liver is one of the few organs in which the parenchymal cells communicate directly with the blood. Moreover, the endothelial cells in the sinusoidal space had no connective tissue, and there were many unmembranous fenestration holes with small diameter of 0. 0 渭 m and large diameter of 1 渭 m. Therefore, the hepatic vascular system is permeable, some macromolecules can pass freely, and there is no tight barrier between blood and hepatocytes. Because of the limitation of viral vector safety, gene therapy at present mainly studies non-virus vector. The transfection efficiency of traditional non-viral vectors is low. Chitosan is a novel nano-microcapsule carrier with biodegradability, biocompatibility, high safety and high transfection efficiency. Previous studies have shown that chitosan has a high transfection efficiency in vitro, and in vivo experiments in mice have proved that chitosan transfection efficiency is also very high. However, there is no international literature on the gene transduction of chitosan in large animals. In this study, galactosylated chitosan (GCN) GCU GC molecule with galactose ligand was used to bind to the specific sialic acid glycoprotein receptor (ASGP-R) on the surface of hepatocytes, so as to achieve liver targeting gene transduction.
【学位授予单位】：第四军医大学
【学位级别】：硕士
【学位授予年份】：2005
【分类号】：R346

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