Could mRNA delivery of OAS3 and RNase L provide a novel broad-spectrum antiviral therapy?

• Hypothesizes that mRNA encoding OAS3 and RNase L could selectively activate a host-intrinsic antiviral pathway. • Targets viral double-stranded RNA, enabling a potential broad-spectrum antiviral strategy across diverse virus families. • It circumvents common viral resistance mechanisms that interfere with interferon signaling. The development of novel antiviral drugs is urgently needed due to the high mortality caused by viral infections. Emerging viral strains and highly transmissible pathogens further increase this threat. Recently, the COVID-19 pandemic has resulted in millions of deaths worldwide, and it is highly probable that it will not be the last pandemic to emerge. Therefore, there is a pressing need for new therapeutic options that offer improved efficacy and safety. These options would enable physicians and patients to select the most appropriate treatment for each clinical situation. In this context, the present article aims to encourage discussion and research on the development of innovative antiviral therapeutics by proposing a hypothesis for a novel potential antiviral drug. Specifically, this manuscript explores the concept of using messenger RNA, encapsulated in lipid nanoparticles, to encode 2′,5′-oligoadenylate synthetase 3 and latent ribonuclease. The manuscript also discusses the potential advantages, limitations, and translational considerations of this approach in comparison with existing antiviral therapies.