PanTherapeutics, Route de Lavaux 49, CH1095 Lutry, Switzerland.
Int J Mol Sci. 2022 Dec 9;23(24):15622. doi: 10.3390/ijms232415622.
Self-replicating RNA viruses have become attractive delivery vehicles for therapeutic applications. They are easy to handle, can be rapidly produced in large quantities, and can be delivered as recombinant viral particles, naked or nanoparticle-encapsulated RNA, or plasmid DNA-based vectors. The self-replication of RNA in infected host cells provides the means for generating much higher transgene expression levels and the possibility to apply substantially reduced amounts of RNA to achieve similar expression levels or immune responses compared to conventional synthetic mRNA. Alphaviruses and flaviviruses, possessing a single-stranded RNA genome of positive polarity, as well as measles viruses and rhabdoviruses with a negative-stranded RNA genome, have frequently been utilized for therapeutic applications. Both naturally and engineered oncolytic self-replicating RNA viruses providing specific replication in tumor cells have been evaluated for cancer therapy. Therapeutic efficacy has been demonstrated in animal models. Furthermore, the safe application of oncolytic viruses has been confirmed in clinical trials. Multiple myeloma patients treated with an oncolytic measles virus (MV-NIS) resulted in increased T-cell responses against the measles virus and several tumor-associated antigen responses and complete remission in one patient. Furthermore, MV-CEA administration to patients with ovarian cancer resulted in a stable disease and more than doubled the median overall survival.
自我复制的 RNA 病毒已成为治疗应用的有吸引力的输送载体。它们易于操作，可以大量快速生产，并可以作为重组病毒颗粒、裸露或纳米颗粒包封的 RNA 或基于质粒 DNA 的载体进行传递。感染宿主细胞中的 RNA 自我复制为产生更高的转基因表达水平提供了手段，并且有可能应用大大减少的 RNA 量来达到与传统合成 mRNA 相似的表达水平或免疫反应。具有正单链 RNA 基因组的甲病毒和黄病毒以及具有负链 RNA 基因组的麻疹病毒和弹状病毒经常被用于治疗应用。具有在肿瘤细胞中特异性复制能力的天然和工程化溶瘤自我复制 RNA 病毒已被评估用于癌症治疗。在动物模型中已经证明了治疗功效。此外，溶瘤病毒的安全应用已在临床试验中得到证实。接受溶瘤麻疹病毒 (MV-NIS) 治疗的多发性骨髓瘤患者导致针对麻疹病毒和几种肿瘤相关抗原的 T 细胞反应增加，并使一名患者完全缓解。此外，MV-CEA 给药给卵巢癌患者导致疾病稳定，并使中位总生存期延长一倍以上。
