Bowden-Reid Ellen, Moles Ernest, Kelleher Anthony, Ahlenstiel Chantelle
The Kirby Institute, UNSW Sydney, Sydney, 2052, Australia.
Children's Cancer Institute, Lowy Cancer Research Centre, UNSW Sydney, Sydney, 2052, Australia.
Drug Deliv Transl Res. 2025 Jan 20. doi: 10.1007/s13346-025-01788-x.
Using the knowledge from decades of research into RNA-based therapies, the COVID-19 pandemic response saw the rapid design, testing and production of the first ever mRNA vaccines approved for human use in the clinic. This breakthrough has been a significant milestone for RNA therapeutics and vaccines, driving an exponential growth of research into the field. The development of novel RNA therapeutics targeting high-threat pathogens, that pose a substantial risk to global health, could transform the future of health delivery. In this review, we provide a detailed overview of the two RNA interference (RNAi) pathways and how antiviral RNAi therapies can be used to treat acute or chronic diseases caused by the pandemic viruses SARS-CoV-2 and HIV, respectively. We also provide insights into short-interfering RNA (siRNA) delivery systems, with a focus on how lipid nanoparticles can be functionalized to achieve targeted delivery to specific sites of disease. This review will provide the current developments of SARS-CoV-2 and HIV targeted siRNAs, highlighting strategies to advance the progression of antiviral siRNA along the clinical development pathway.
利用数十年来对基于RNA的疗法的研究知识，在应对新冠疫情期间，首款获批用于人体临床的mRNA疫苗得以迅速设计、测试和生产。这一突破是RNA疗法和疫苗领域的一个重要里程碑，推动了该领域研究呈指数级增长。开发针对对全球健康构成重大风险的高威胁病原体的新型RNA疗法，可能会改变医疗服务的未来。在这篇综述中，我们详细概述了两种RNA干扰（RNAi）途径，以及抗病毒RNAi疗法如何分别用于治疗由大流行病毒SARS-CoV-2和HIV引起的急性或慢性疾病。我们还深入探讨了小干扰RNA（siRNA）递送系统，重点关注如何对脂质纳米颗粒进行功能化修饰，以实现靶向递送至疾病的特定部位。这篇综述将介绍针对SARS-CoV-2和HIV的siRNA的当前进展，突出推进抗病毒siRNA沿临床开发路径发展的策略。
