Kirby Institute, UNSW, Sydney, NSW 2052, Australia.
Respiratory Technology, Woolcock Institute of Medical Research, Sydney, NSW 2037, Australia.
Int J Mol Sci. 2022 Feb 22;23(5):2408. doi: 10.3390/ijms23052408.
Since December 2019, a pandemic of COVID-19 disease, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has rapidly spread across the globe. At present, the Food and Drug Administration (FDA) has issued emergency approval for the use of some antiviral drugs. However, these drugs still have limitations in the specific treatment of COVID-19, and as such, new treatment strategies urgently need to be developed. RNA-interference-based gene therapy provides a tractable target for antiviral treatment. Ensuring cell-specific targeted delivery is important to the success of gene therapy. The use of nanoparticles (NPs) as carriers for the delivery of small interfering RNA (siRNAs) to specific tissues or organs of the human body could play a crucial role in the specific therapy of severe respiratory infections, such as COVID-19. In this review, we describe a variety of novel nanocarriers, such as lipid NPs, star polymer NPs, and glycogen NPs, and summarize the pre-clinical/clinical progress of these nanoparticle platforms in siRNA delivery. We also discuss the application of various NP-capsulated siRNA as therapeutics for SARS-CoV-2 infection, the challenges with targeting these therapeutics to local delivery in the lung, and various inhalation devices used for therapeutic administration. We also discuss currently available animal models that are used for preclinical assessment of RNA-interference-based gene therapy. Advances in this field have the potential for antiviral treatments of COVID-19 disease and could be adapted to treat a range of respiratory diseases.
自 2019 年 12 月以来，一种由严重急性呼吸系统综合征冠状病毒 2（SARS-CoV-2）引起的 COVID-19 疾病大流行迅速在全球范围内蔓延。目前，食品和药物管理局（FDA）已紧急批准使用一些抗病毒药物。然而，这些药物在 COVID-19 的具体治疗中仍然存在局限性，因此迫切需要开发新的治疗策略。基于 RNA 干扰的基因治疗为抗病毒治疗提供了一个可行的目标。确保细胞特异性靶向递送对于基因治疗的成功至关重要。利用纳米颗粒（NPs）作为载体将小干扰 RNA（siRNAs）递送到人体的特定组织或器官，可能在 COVID-19 等严重呼吸道感染的特异性治疗中发挥关键作用。在这篇综述中，我们描述了各种新型纳米载体，如脂质 NPs、星形聚合物 NPs 和糖原 NPs，并总结了这些纳米颗粒平台在 siRNA 递送上的临床前/临床进展。我们还讨论了各种 NP 包裹的 siRNA 作为 SARS-CoV-2 感染治疗剂的应用、将这些治疗剂靶向递送到肺部的局部递送的挑战以及用于治疗给药的各种吸入装置。我们还讨论了目前用于 RNA 干扰基因治疗临床前评估的动物模型。该领域的进展有可能用于 COVID-19 疾病的抗病毒治疗，并可用于治疗一系列呼吸道疾病。
