PanTherapeutics, Lutry, Switzerland.
Int Rev Cell Mol Biol. 2022;372:97-157. doi: 10.1016/bs.ircmb.2022.03.006. Epub 2022 Aug 17.
Self-replicating RNA viral vectors have been engineered for both prophylactic and therapeutic applications. Mainly the areas of infectious diseases and cancer have been targeted. Both positive and negative strand RNA viruses have been utilized including alphaviruses, flaviviruses, measles viruses and rhabdoviruses. The high-level of RNA amplification has provided efficient expression of viral surface proteins and tumor antigens. Immunization studies in animal models have elicit robust neutralizing antibody responses. In the context of infectious diseases, immunization with self-replicating RNA viral vectors has provided protection against challenges with lethal doses of pathogens in animal models. Similarly, immunization with vectors expressing tumor antigens has resulted in tumor regression and eradication and protection against tumor challenges in animal models. The transient nature and non-integration of viral RNA into the host genome are ideal features for vaccine development. Moreover, self-replicating RNA viral vectors show great flexibility as they can be applied as recombinant viral particles, RNA replicons or DNA replicon plasmids. Several clinical trials have been conducted especially in the area of cancer immunotherapy.
自复制 RNA 病毒载体已被用于预防和治疗应用。主要针对传染病和癌症领域。已利用正链和负链 RNA 病毒，包括甲病毒、黄病毒、麻疹病毒和弹状病毒。高水平的 RNA 扩增提供了病毒表面蛋白和肿瘤抗原的高效表达。动物模型中的免疫研究引起了强烈的中和抗体反应。在传染病方面，用自复制 RNA 病毒载体免疫可提供针对动物模型中致死剂量病原体挑战的保护。同样，用表达肿瘤抗原的载体免疫导致肿瘤消退和消除，并提供针对动物模型中肿瘤挑战的保护。病毒 RNA 短暂存在且不整合到宿主基因组中是疫苗开发的理想特征。此外，自复制 RNA 病毒载体具有很大的灵活性，因为它们可以作为重组病毒颗粒、RNA 复制子或 DNA 复制子质粒应用。已经进行了几项临床试验，特别是在癌症免疫治疗领域。
