血管内皮生长因子受体介导的靶向性非病毒载体的改进与体内 …

目的 通过构建一种有相对靶向性的基因治疗载体，将外源基因导入新生血管内皮细胞，为开展靶向于肿瘤新生血管的基因治疗奠定基础。方法 根据血管内皮生长因子（ＶＥＧＦ）与ＶＥＧＦ受体结合位点，修改本实验室已有的酸体寡肽ＧＶ１、ＧＶ２氨基酸序列，并合成了基因转移载体系统。用载体包裹外源ＤＮＡ（β－ｇａｌ），进行体内实验，观察外源基因在体内的分布和不同时间的表达情况。结果 报告基因在心、肺、肝和肾中无明显地表

Modified vascular endothelia growth factor receptor-mediated targeting nonviral gene delivery system and in vivo

OBJECTIVE: To investigate whether the modified vascular endothelial growth factor (VEGF) receptor-mediated targeting nonviral gene delivery system is efficient in transducing exogenous gene. METHODS: We detected the expression of VEGF receptor on some tumor models by immunohistochemistry at first and selected nine models, i.e. SMMC-7721, SK-OV-3, H128, SPC-A1, LoVo, MKN-45, BCaP-37, A375, cervical cancer xenograft and hepatoma xenograft. Then we prepared two complexes, GV1-P.L./beta-gal and GV2-P.L./beta-gal, and injected the two complexes subcutaneously into nude mice around the tumor. The expression of the reporter gene was observed in the vascular endothelial cells and some tumor cells with highly expressed VEGF receptor. RESULTS: GV2 gene delivery system could transduce exogenous gene into vascular endothelial cells and subcutaneously transplanted tumors such as SK-OV-3, and cervical xenograft which were rich of VEGF receptor on the surface of the tumor cell. The expression reached a high level at day 3 and decreased eventually until the 3(rd) week. There was no expression in the heart and lung but low expression was seen in the spleen. GV1 gene delivery system also transduced exogenous gene into the endothelial cells but with low efficiency. CONCLUSION: This system can specifically transduce beta-gal to cells rich of VEGF receptor but not to cells with undetectable VEGF receptor. The targetability of this modified system is increased as compared to the system previously reported.