Idres Yusuf M, Idris Adi, Gao Wenqing
Centre for Immunology and Infection Control, School of Biomedical Sciences, Queensland University of Technology, Brisbane, QLD, Australia.
Drug Deliv Transl Res. 2025 Feb 25. doi: 10.1007/s13346-025-01815-x.
The advent of RNA interference (RNAi) technology through the use of short-interfering RNAs (siRNAs) represents a paradigm shift in the fight against viral infections. siRNAs, with their ability to directly target and silence specific posttranscriptional genes, offer a novel mechanism of action distinct from that of traditional pharmacotherapeutics. This review delves into the growing field of siRNA therapeutics against viral infections, highlighting their critical role in contemporary antiviral strategies. Importantly, this review will solely focus on the use of lipid nanoparticles (LNPs) as the ideal antiviral siRNA delivery agent for use in vivo. We discuss the challenges of siRNA delivery and how LNPs have emerged as a pivotal solution to enhance antiviral efficacy. Specifically, this review focuses on work that have preclinically tested LNP formulated siRNA on virus infection animal models. Since the COVID-19 pandemic, we have witnessed a resurgence in the field of RNA-based therapies, including siRNAs against viruses including, SARS-CoV-2. Notably, the critical importance of LNPs as the ideal carrier for precious 'RNA cargo' can no longer be ignored with the advent of mRNA-LNP based COVID-19 vaccines. siRNA-based therapeutics represents an emerging class of anti-infective drugs with a foreseeable future as suitable antiviral agents.
通过使用小干扰RNA（siRNA）实现的RNA干扰（RNAi）技术的出现，代表了抗击病毒感染斗争中的范式转变。siRNA能够直接靶向并沉默特定的转录后基因，提供了一种不同于传统药物治疗的新型作用机制。本综述深入探讨了针对病毒感染的siRNA治疗这一不断发展的领域，强调了它们在当代抗病毒策略中的关键作用。重要的是，本综述将仅聚焦于使用脂质纳米颗粒（LNP）作为体内使用的理想抗病毒siRNA递送剂。我们讨论了siRNA递送的挑战以及LNP如何成为提高抗病毒疗效的关键解决方案。具体而言，本综述重点关注在病毒感染动物模型上对LNP配制的siRNA进行临床前测试的工作。自新冠疫情以来，我们见证了基于RNA的疗法领域的复兴，包括针对包括SARS-CoV-2在内的病毒的siRNA。值得注意的是，随着基于mRNA-LNP的新冠疫苗的出现，LNP作为珍贵“RNA货物”的理想载体的至关重要性再也不能被忽视。基于siRNA的疗法代表了一类新兴的抗感染药物，作为合适的抗病毒剂具有可预见的未来。
