Manipulation of high-density lipoprotein structure and function for development of gene delivery carrier

我们在这项研究中的目的是利用人体内的天然纳米材料，开发能够将治疗性基因输送到所需部位的纳米材料，例如癌症组织。高密度脂蛋白(高密度脂蛋白)是一种天然的纳米材料，它将脂质从周围组织输送到我们体内的肝脏。由于其生理功能，高密度脂蛋白有通过高密度脂蛋白受体识别高密度脂蛋白中载脂蛋白A-I部分在肝脏中蓄积的倾向。我们设计了9个apoA-I缺失突变体，成功制备了8个高密度脂蛋白突变体，以削弱肝脏的这种识别作用，进而将高密度脂蛋白重定向至所需的位点。其中，少数高密度脂蛋白突变体与高密度脂蛋白受体的亲和力降低。

Our purpose in this study is to develop nanomaterials capable of delivering therapeutic gene to desired sites, such as cancer tissues, by utilizing natural nanomaterials in our body. High-density lipoprotein (HDL) is a natural nanomaterial that delivers lipids from peripheral tissues to the liver in our body. Due to its physiological functions, HDL have a propensity to accumulate in liver via HDL receptor recognition of apoA-I moiety in HDL. In order to weaken this recognition in the liver and then to redirect HDL to desired sites, we designed 9 apoA-I deletion mutants and succeeded in preparation of 8 HDL mutants. Among them, a few HDL mutants were found to show decreased affinity to the HDL receptor.