多肽修饰聚乙烯亚胺基因载体的研究

项目名称： 多肽修饰聚乙烯亚胺基因载体的研究

项目编号： No.21472131

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 环境科学、安全科学

项目作者： 余孝其

作者单位： 四川大学

项目金额： 90万元

中文摘要： 基因治疗是通过载体将目的基因传递到特定的组织细胞（靶细胞）内进行适当表达以治疗疾病的一种方法，聚乙烯亚胺是一种研究广泛的具有潜能的非病毒基因载体，但是其细胞毒性较大，在血清条件下不稳定，转染效率不够高以及靶向性差等限制了其应用。我们在前期的研究工作中合成了系列聚乙烯亚胺类似结构的聚合物，在一定程度上提高了转染效率和血清稳定性，降低了细胞毒性。基于多肽的功能多样性、生物相容性、稳定性和靶向性，本项目拟用氨基酸、寡肽和多肽修饰聚乙烯亚胺，围绕改善DNA结合保护能力、提高细胞转染效率，增强基因载体在体内传递时的稳定性和降低载体的细胞毒性等核心问题开展系统而深入地研究。将对其作为非病毒型载体的结构活性关系、运载过程和机理等一系列问题进行探讨，为设计安全、高效、低毒、靶向的非病毒基因载体提供新的前景和理论基础。

中文关键词： 化学生物学；生物有机化学；纳米结构；抗肿瘤；化学修饰

英文摘要： Gene therapy is a method for the treatment of disease to delivery gene to a specific tissue cells (target cells) by carriers and the gene will take appropriate expression. Polyethylene imine is a kind of extensive research compound and should be potential as non-virus gene carrier. Due to its cytotoxicity, instability under the condition of serum and poor transfection efficiency it have not been developed for further application. In our previous research work, we have synthesized a series of polymers which structures are very similar to polyethylene imine. These compounds have improved their transfection efficiency and serum stability, reduced the cytotoxicity in a certain extent. Based on the function diversity, biocompatibility, stability and targeting property of polypeptide, this project employs amino acids, oligopeptides and peptides to modify polyethylene imine. We will carry out the systematic and in-depth research in improving DNA protection ability, cell transfection efficiency, the stability and reducing the cytotoxicity of gene carrier in the body. And we will explore the structure-activity relationship of these modified polyethylene imines as non-virus carriers, the delivery process and mechanism will also be discussed. All above-mentioned research will provide us new prospect and theoretical basis for the design of non-virus gene carriers with safety, high efficiency, low toxicity and targeting property.

英文关键词： Chemical Biology;Bioorganic Chemistry;Nanostructure;Antitumor;Chemical Modification