Department of Biochemistry and Molecular Biology, University of South Alabama, College of Medicine, MSB 2370, 307 University Boulevard, Mobile, AL 36688-0002, USA.
Viruses. 2010 Jul;2(7):1448-1457. doi: 10.3390/v2071448. Epub 2010 Jul 9.
Influenza virus is one of the most prevalent and ancient infections in humans. About a fifth of world's population is infected by influenza virus annually, leading to high morbidity and mortality, particularly in infants, the elderly and the immunocompromised. In the US alone, influenza outbreaks lead to roughly 30,000 deaths each year. Current vaccines and anti-influenza drugs are of limited use due to high mutation rate of the virus and side effects. In recent years, RNA interference, triggered by synthetic short interfering RNA (siRNA), has rapidly evolved as a potent antiviral regimen. Properly designed siRNAs have been shown to function as potent inhibitors of influenza virus replication. The siRNAs outperform traditional small molecule antivirals in a number of areas, such as ease of design, modest cost, and fast turnaround. Although specificity and tissue delivery remain major bottlenecks in the clinical applications of RNAi in general, intranasal application of siRNA against respiratory viruses including, but not limited to influenza virus, has experienced significant success and optimism, which is reviewed here.
流感病毒是人类最普遍和古老的感染之一。每年约有五分之一的世界人口感染流感病毒,导致发病率和死亡率高,特别是在婴儿、老年人和免疫功能低下者中。仅在美国,流感爆发每年导致约 30000 人死亡。由于病毒的高突变率和副作用,目前的疫苗和抗流感药物的使用效果有限。近年来,由合成短干扰 RNA(siRNA)触发的 RNA 干扰已迅速成为一种有效的抗病毒方案。经过适当设计的 siRNA 已被证明是一种有效的流感病毒复制抑制剂。siRNA 在许多方面优于传统的小分子抗病毒药物,例如设计简单、成本适中、周转时间快。尽管 RNAi 在临床应用中的特异性和组织递送仍然是主要瓶颈,但针对包括但不限于流感病毒的呼吸道病毒的 siRNA 鼻腔内应用已经取得了显著的成功和乐观的前景,本文对此进行了综述。