PanTherapeutics, Rte de Lavaux 49, CH1095 Lutry, Switzerland.
Genes (Basel). 2019 Mar 1;10(3):189. doi: 10.3390/genes10030189.
RNA viruses have been subjected to substantial engineering efforts to support gene therapy applications and vaccine development. Typically, retroviruses, lentiviruses, alphaviruses, flaviviruses rhabdoviruses, measles viruses, Newcastle disease viruses, and picornaviruses have been employed as expression vectors for treatment of various diseases including different types of cancers, hemophilia, and infectious diseases. Moreover, vaccination with viral vectors has evaluated immunogenicity against infectious agents and protection against challenges with pathogenic organisms. Several preclinical studies in animal models have confirmed both immune responses and protection against lethal challenges. Similarly, administration of RNA viral vectors in animals implanted with tumor xenografts resulted in tumor regression and prolonged survival, and in some cases complete tumor clearance. Based on preclinical results, clinical trials have been conducted to establish the safety of RNA virus delivery. Moreover, stem cell-based lentiviral therapy provided life-long production of factor VIII potentially generating a cure for hemophilia A. Several clinical trials on cancer patients have generated anti-tumor activity, prolonged survival, and even progression-free survival.
RNA 病毒已被广泛用于基因治疗应用和疫苗开发的工程改造。通常，逆转录病毒、慢病毒、甲病毒、黄病毒、弹状病毒、麻疹病毒、新城疫病毒和小 RNA 病毒已被用作表达载体，用于治疗各种疾病，包括不同类型的癌症、血友病和传染病。此外，利用病毒载体进行疫苗接种可评估针对传染性病原体的免疫原性和保护作用，以对抗致病性生物。在动物模型中的几项临床前研究证实了针对致命性挑战的免疫反应和保护作用。同样，在植入肿瘤异种移植物的动物中施用 RNA 病毒载体可导致肿瘤消退和延长生存时间，在某些情况下还可完全清除肿瘤。基于临床前研究结果，已进行临床试验以确定 RNA 病毒递送的安全性。此外，基于干细胞的慢病毒疗法可长期产生因子 VIII，从而可能治愈血友病 A。对癌症患者进行的几项临床试验已产生抗肿瘤活性、延长生存时间，甚至无进展生存期。
