文章：

利用裂谷热病毒NSs基因进行癌症基因治疗

Harnessing Rift Valley fever virus NSs gene for cancer gene therapy 

原文发布日期：2022-04-07 

英文摘要：

One of the greatest challenges in the treatment of cancer is tumor heterogeneity which results in differential responses to chemotherapy and drugs that work through a single pathway. A therapeutic agent that targets cancer cells for death through multiple mechanisms could be advantageous as a broad inhibitor for many types of cancers and the heterogeneous alterations they possess. Several viral proteins have been exploited for antiproliferative and apoptotic effect in cancer cells by disrupting critical survival pathways. Here, we report the use of the non-structural protein on the S segment (NSs) gene from the Rift Valley fever virus (RVFV) to induce cancer cell death. NSs has immune evasion functions in the context of RVFV with many of these functions affecting proliferation pathways and DNA damage signaling, which could be leveraged against cancer cells. We find that expression of NSs in multiple cancer cell lines leads to a rapid decline in cell viability and induction of apoptosis. Interestingly, we observed reduced toxicity in normal cells suggesting cancer cells may be more susceptible to NSs-mediated cell death. To enhance specificity of NSs for use in hepatocellular carcinoma, we incorporated four miR-122 binding sites in the 3’ untranslated region (UTR) of the NSs mRNA to achieve cell type specific expression. Observations presented here collectively suggest that delivery of the NSs gene may provide a unique therapeutic approach in a broad range of cancers. 

摘要翻译： 

癌症治疗中的最大挑战之一是肿瘤异质性，这导致对化疗和单一通路药物产生差异性反应。一种通过多重机制靶向癌细胞死亡的治疗剂，可能作为广谱抑制剂对多种癌症类型及其异质性改变具有优势。多种病毒蛋白已被利用通过破坏关键生存通路来在癌细胞中发挥抗增殖和促凋亡作用。本文报道利用裂谷热病毒（RVFV）S片段非结构蛋白（NSs）基因诱导癌细胞死亡。NSs在RVFV感染中具有免疫逃逸功能，其中许多功能影响增殖通路和DNA损伤信号传导，这些机制可被用于对抗癌细胞。我们发现，在多种癌细胞系中表达NSs会导致细胞活力快速下降并诱导凋亡。值得注意的是，在正常细胞中观察到毒性较低，表明癌细胞可能对NSs介导的细胞死亡更为敏感。为增强NSs在肝细胞癌中的应用特异性，我们在NSs mRNA的3'非翻译区（UTR）引入了四个miR-122结合位点以实现细胞类型特异性表达。本研究结果共同表明，NSs基因的递送可能为广泛癌症类型提供一种独特的治疗策略。

原文链接：

Harnessing Rift Valley fever virus NSs gene for cancer gene therapy