Thomas Mini, Ge Qing, Lu James J, Klibanov Alexander M, Chen Jianzhu
Division of Biological Engineering, Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Expert Opin Biol Ther. 2005 Apr;5(4):495-505. doi: 10.1517/14712598.5.4.495.
Influenza A virus causes one of the most prevalent infections in humans. In a typical year, 10-20% of the population of the US is infected by influenza virus, resulting in up to 40,000 deaths and 200,000 hospitalisations. Vaccination is the most effective preventative measure that can protect 70-90% of healthy adults aged < 65; however, the protection rate is much lower in those most susceptible to infection, namely infants, the elderly and individuals with weakened immune systems. Although four drugs have been approved by the FDA for use as prophylaxis and/or treatment of influenza, concerns about their side effects and the emergence of drug-resistant viruses persist. RNA interference (RNAi), an emerging method of post transcriptional gene silencing, appears ideal for the prevention and treatment of influenza. RNAi in mammals can be mediated by short interfering RNAs (siRNAs) of approximately 21-27 nucleotides in length. The authors have previously shown that siRNAs specific for conserved regions of the influenza virus genome are potent inhibitors of influenza virus replication in both cell lines and chicken embryos. This review discusses the recent progress in the in vivo inhibition of influenza virus by the delivery of siRNAs mediated by non-viral vectors, and the prospects of this strategy for prophylaxis and treatment of influenza infection in humans.
甲型流感病毒是人类中最常见的感染源之一。在典型年份，美国10%至20%的人口会感染流感病毒，导致多达4万人死亡和20万人住院治疗。接种疫苗是最有效的预防措施，可保护70%至90%的65岁以下健康成年人；然而，在最易感染的人群中，即婴儿、老年人和免疫系统较弱的个体中，保护率要低得多。尽管美国食品药品监督管理局（FDA）已批准四种药物用于预防和/或治疗流感，但对其副作用以及耐药病毒出现的担忧依然存在。RNA干扰（RNAi）是一种新兴的转录后基因沉默方法，似乎是预防和治疗流感的理想选择。哺乳动物中的RNAi可由长度约为21至27个核苷酸的小干扰RNA（siRNA）介导。作者先前已表明，针对流感病毒基因组保守区域的siRNA是细胞系和鸡胚中流感病毒复制的有效抑制剂。本文综述了通过非病毒载体介导递送siRNA在体内抑制流感病毒方面的最新进展，以及该策略在预防和治疗人类流感感染方面的前景。
