Expression of a fusogenic membrane glycoprotein by an oncolytic herpes simplex virus potentiates the viral antitumor effect
Expression of a fusogenic membrane glycoprotein by an oncolytic herpes simplex virus potentiates the viral antitumor effect
复制标题
DOI：
10.1016/s1525-0016(03)00092-3
复制
发表时间：
2003-06-01
影响因子：
12.4
通讯作者：
Zhang, XL
中科院分区：
文献类型：
--
作者：
Fu, XP;Tao, L;Zhang, XL
溶瘤病毒在实体瘤的治疗中显示出相当大的前景，但如果要充分发挥其临床潜力，必须提高它们的效力。我们使用强制连接程序将长臂猿白血病病毒囊膜融合膜糖蛋白(GALV.fus)的截短型基因插入到溶瘤单纯疱疹病毒中。随后的体外和体内研究表明，在溶瘤病毒的背景下表达GALV.fus显著增强了病毒的抗肿瘤作用。此外，通过严格的晚期病毒启动子控制GALV.fus的表达，我们能够在肿瘤细胞中表达这种糖蛋白，但不能在正常的未分裂细胞中表达。证实溶瘤单纯疱疹病毒功能表达强融合基因是否在不增加其毒性的情况下增强病毒抗肿瘤活性将是有意义的。
Oncolytic viruses have shown considerable promise in the treatment of solid tumors, but their potency must be improved if their full clinical potential is to be realized. We inserted the gene encoding a truncated form of the gibbon ape leukemia virus envelope fusogenic membrane glycoprotein (GALV.fus) into an oncolytic herpes simplex virus, using an enforced ligation procedure. Subsequent in vitro and in vivo studies showed that expression of GALV.fus in the context of an oncolytic virus significantly enhances the antitumor effect of the virus. Furthermore, by controlling GALV.fus expression through a strict late viral promoter, whose activity depends on the initiation of viral DNA replication, we were able to express this glycoprotein in tumor cells but not in normal nondividing cells. It will be of interest to confirm whether functional expression of a strong fusogenic gene by an oncolytic herpes simplex virus enhances viral antitumor activity without increasing its toxicity.