新型糖类脂质体靶向基因载体的设计、合成及转染性能研究

项目名称： 新型糖类脂质体靶向基因载体的设计、合成及转染性能研究

项目编号： No.21272064

项目类型： 面上项目

立项/批准年度： 2013

项目学科： 数理科学和化学

项目作者： 曾佑林

作者单位： 湖南师范大学

项目金额： 80万元

中文摘要： 基因治疗的关键是构建高效、安全的靶向基因载体。本课题结合脂质体基因载体的优点和糖基靶向识别功能，设计并合成全新的糖类脂质体靶向基因载体，深入研究载体的转染性能与细胞靶向性。通过考察糖类脂质体载体携带绿色荧光蛋白基因质粒在各肿瘤细胞系内的表达情况，确定载体单糖结构与靶细胞之间的对应关系；通过考察糖类脂质体的疏水链长度、连接臂长度、亲水端种类和密度、表面电势、pH值、粒径大小及粒径分布等化学与物理结构参数对转染性能的影响，建立糖类脂质体基因载体化学结构和物理结构与转染性能和靶向性能之间的关系，并应用于糖类脂质体靶向基因载体系统以及其它类型的类阳离子脂质体靶向基因载体系统的设计，为新型糖类脂质体及其它类型脂质体非病毒靶向转基因载体的构建及其应用提供技术支撑。

中文关键词： 糖类脂质体基因载体；转染性能评价；构效关系；；

英文摘要： The key techlonodgy for gene therapy is to design an effective and safe vector for targeted gene delivery. Based the merits of the liposomes gene delivery vectors and the potential targeting recognition capabilities of monosaccharide, a kind of novel glycolipids targeted gene delivery systems will be designed, synthesized in this proposal. The tansfection properties and targeted assay of those glycolipids gene vectors will be investigated. The correspondence between monosaccharides and targeting cells will be discovered by observing enhanced green fluorescent protein (EGFP) expression from pEGFP-C1 plasmid in HEK293, 293FT, GES-1, GC-1, SW-480, HT-1080, U251, 3T3-L1, MCF-7, Hct-116, HUVEC, HeLa, A549, HBL100-SV40 and NIH3T3 cells. And a structure-activity relationship based on the chemical structure and physical structure of glucolipids gene delivery vectors will be established by evaluating the effects of the chemical structure and physical structure such as length of hydrophobic chain, length of the linkage between hydrophilic terminal and hydrophobic terminal, hydrophilic terminal types, hydrophilic terminal density, surface zeta potential, particle size and size distribution, on the transfection properties. This structure-activity relationship will be to provide a guiding theory for constructing new cationic

英文关键词： Glycolipid gene delivery vector；Transfection properties assay；Structure-activity relationship；；