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.