经NGR肽段遗传修饰的携带三种报告基因的腺病毒载体的构建及其实验研究  

Construction of NGR Peptide Genetically Modified Adenovirus Vector Expressing Three Reporter Genes and Its Experimental Study

作　　者：冯飞雪[1] 赵俊丽[1] 王东阳[1] 刘世海[1] 王丽娴[1] 夏海滨[1] 

机构地区：[1]陕西师范大学生命科学学院基因治疗研究室,西安710062

出　　处：《中国生物工程杂志》2011年第4期25-30,共6页China Biotechnology

基　　金：国家自然科学基金(30872993)资助项目

摘　　要：NGR(Asn-Gly-Arg)是通过噬菌体展示技术筛选出来的能够和肿瘤新生血管特异结合的三肽模体,可以将多种药物分子和病毒载体靶向运输到肿瘤或者进行血管再生的组织中。为此构建了腺病毒衣壳蛋白knob的HI环(HI-loop)经NGR肽段修饰的并同时表达三种报告基因的腺病毒载体Ad5/E1-mCherry/E3-luciferase-2A-eGFP/knob-NGR。体内、外实验研究表明,该病毒载体可成功表达三种报告基因;经NGR肽段修饰的腺病毒载体对人乳腺癌细胞系MDA-MB-231的感染效率高于未经修饰的对照腺病毒Ad5CMVeGFP。该载体的成功构建为进一步研究经NGR肽段修饰的腺病毒在肿瘤动物模型体内的靶向性及经NGR肽段修饰的并携带治疗基因的实验治疗研究奠定了基础。NGR（Asn-Gly-Arg） motif exploited by phage display can selectively recognize neovasculature,and can be used for ligand-directed targeted delivery of various drugs and viral vectors to tumors or to other tissues with an angiogenesis process.Therefore,constructed the adenoviral vector Ad5/E1-mCherry/E3-luciferase-2A-eGFP/fiber-NGR which was modified with NGR peptide in the HI loop of the knob and could express three reporter genes.The study of the adenovirus in vitro and in vivo indicated that the three reporter genes could be expressed successfully and the infection efficiency indicated human breast cancer cell line MDA-MB-231 mediated by constructed adenovirus was higher than that mediated by unmodified control adenovirus Ad5CMVeGFP.The construction of the adenoviral vector laid a foundation for the further research on the target of adenoviral vector modified with NGR peptide and the therapy research of adenoviral vector carrying therapeutic genes in tumor animal model.

关 键 词：腺病毒载体 NGR肽段 衣壳蛋白遗传修饰 肿瘤基因治疗 

分 类 号：Q789[生物学—分子生物学]