文章：

利用逆转录病毒复制载体进行双载体前药激活剂基因治疗

Dual-vector prodrug activator gene therapy using retroviral replicating vectors 

原文发布日期：2018-10-22

英文摘要：

Retroviral replicating vectors (RRVs) have been shown to achieve efficient tumor transduction and enhanced therapeutic benefits in a variety of cancer models. In the present study, we evaluated a possible combinatorial effect of prodrug activator genes delivered by two different RRVs derived from amphotropic murine leukemia virus (AMLV) and gibbon ape leukemia virus (GALV) on human hepatocellular carcinoma Hep3B cells. Both RRVs showed efficient replicative spread in culture and can overcame superinfection resistance each other. Notably, the replication and spread of each RRV in culture remained unaffected by pretransduction with the counterpart RRV. We further transduced cells with RRVs which individually possessed the prodrug activator genes yeast cytosine deaminase (CD) and herpes simplex virus thymidine kinase (TK) alone or in combination, and evaluated the cytotoxic effects of RRV-mediated gene therapy with CD and TK in the presence of the respective prodrugs, 5-fluorocytosine and ganciclovir. All combinations of the two prodrug activator genes produced synergistic cytocidal effects, but the combined effects of the different genes were significantly greater than those of the same genes when delivered by two different vectors. The present findings indicate the potential utility of dual-vector gene therapy using two different RRVs carrying different prodrug activator genes. 

摘要翻译：

逆转录病毒复制载体（RRV）已在多种癌症模型中展现出高效的肿瘤转导能力和增强的治疗效果。本研究评估了由两株不同RRV（分别源自嗜亲性小鼠白血病病毒AMLV和长臂猿白血病病毒GALV）所携带的前药激活基因组合对人肝癌Hep3B细胞的协同作用。两种RRV在培养体系中均表现出高效复制扩散能力，并能克服相互间的超感染抵抗。值得注意的是，预先转导其中一种RRV并不会影响另一种RRV的复制和扩散。我们进一步用分别携带酵母胞嘧啶脱氨酶（CD）和单纯疱疹病毒胸苷激酶（TK）前药激活基因的RRV单独或联合转导细胞，并在对应前药5-氟胞嘧啶和更昔洛韦存在条件下评估RRV介导的基因治疗效果。所有双前药激活基因组合均产生协同杀伤效应，但不同基因联合使用时的效果显著优于相同基因通过不同载体递送的效果。本研究结果表明，采用携带不同前药激活基因的双RRV载体进行联合基因治疗具有潜在应用价值。

原文链接：

Dual-vector prodrug activator gene therapy using retroviral replicating vectors