肿瘤靶向基因治疗是当前国际上的研究热点。我们课题组研究发现编码水泡口炎病毒基质蛋白（VSVMP）的基因可诱导肿瘤细胞凋亡，在肿瘤治疗中有潜在应用（ACS Nano 2010, IF=12; FASEB J 2008, IF=5.5;等9篇文章）。本课题中，为进一步提高VSVMP基因治疗肿瘤的作用，我们将激发抗肿瘤免疫的IL-12基因与VSVMP基因共表达在真核载体上，采用一种靶向可控基因治疗技术（端粒酶逆转录酶启动子调控基因在肿瘤细胞选择性表达，新型可降解聚乙烯亚胺纳米粒靶向导入基因到肿瘤细胞），构建了一种新型的VSVMP和IL-12双基因靶向制剂，并初步发现膀胱灌注该制剂可显著抑制膀胱癌原位移植瘤的生长且未引起明显毒副作用。下一步，我们将深入研究VSVMP和IL-12双基因制剂对膀胱癌的靶向性和治疗膀胱癌的作用及机理，为肿瘤靶向基因治疗研究提供新思路，为膀胱癌治疗提供潜在新选择。

Currently, targeted gene therapy of cancer is one of the research focuses. In the past research, our research group found that the plasmid expressing vesicular stomatitis virus matrix protein (VSVMP) can induce apoptosis of cancer cells, showing promising application in cancer therapy（nine papers including ACS Nano 2010 and FASEB J 2008）. In this project, to improve the anticancer effect of VSVMP gene, we colon VSVMP gene and IL-12 gene in the same eukaryotic expression vector, in which IL-12 gene can activiate the anticancer immune response. Moreover, we use a targeted and controlled gene therapy technology (the selective expression of gene in cancer cells is regulated by the telomerase reverse transcriptase promoter, and the targeted delivery of gene into cancer cells is achieved by a novel degradable polyethyleneimine-derived nanoparticle）. Now, we have already got a new targeted gene formulation for VSVMP and IL-12 daul gene plasmid, and preliminarily found that it could efficently inhibit the growth of the orthotopic bladder cancer xenografts and did not cause significant side effect. In our future work, we plan to deeply study the target efficiency, anticancer effect and machanism of this novel VSVMP and IL-2 daul gene formulation against bladder cancer, with the goal of demonstrating a new idea for designing targeted cancer gene therapy protocol and providing a potential candidate for bladder cancer therapy.