4月2日，国际知名学术期刊Gene Therapy在线发表了中科院上海巴斯德研究所抗感染免疫与疫苗研究课题组的研究论文“Adenovirus-mediated Artificial MicroRNAs Targeting Matrix or Nucleoprotein Genes Protect Mice against Lethal Influenza Virus Challenge”。
流感病毒可感染包括人、禽类等多种宿主。据统计，全球每年约有300-500万流感重症患者，其中死亡人数达50万。流感病毒传播迅速，流行广泛，致病性强，对人类健康构成严重威胁，是当今世界最为严重的公共卫生问题之一。研发流感疫苗是预防和控制流感感染和传播的最有效方式，由于流感病毒变异迅速，研发新型、高效、通用型流感疫苗成为流感研究领域中的热点。
上海巴斯德研究所抗感染免疫与疫苗研究课题组博士后张洪波、博士研究生唐昕莹等在周东明研究员的指导下，通过软件设计和细胞体外筛选获得7条针对流感保守基因NP、M1和M2并具有高效拮抗的miRNA，分别为M1-89、 M2-117、 NP-856、NP-969、M1-89+M2-117、M1-89+NP-856和M1-89+NP-969，将筛选获得的miRNA克隆至复制缺陷型AdC68 E1区表达，获得7株表达不同流感特异的miRNA的腺病毒。以1011vp AdC68-amiRNA免疫小鼠，对同源的H1N1流感感染有100%的保护效果，对于异源的H5N1和H9N2也有部分保护效果(40%-100%)。该研究结果证明靶向流感保守片段的miRNA可作为流感防控的新手段。
AdC68-amiRNAs对流感毒株PR8攻击感染具有保护效果
该项研究得到中国科学院上海生命科学研究院植物生理生态研究所王佳伟研究员的支持和帮助，获得国家自然科学基金委员会生命科学部面上项目、中科院百人计划、国家863项目和上海巴斯德健康研究基金会科研项目等经费支持。
原文链接：Adenovirus-mediated artificial microRNAs targeting matrix or nucleoprotein genes protect mice against lethal influenza virus challenge
原文摘要：Influenza virus (IV) infection is a major public health problem, causing millions of cases of severe illness and as many as 500,000 deaths each year worldwide. Given the limitations of current prevention or treatment of acute influenza, novel therapies are needed. RNA interference (RNAi) through microRNAs is an emerging technology that can suppress virus replication in vitro and in vivo. Here, we describe a novel strategy for treatment of infuenza based on RNAi delivered by a replication-defective adenovirus (Ad) vector, derived from chimpanzee serotype 68 (AdC68). Our results showed that artificial microRNAs (amiRNAs) specifically targeting conserved regions of the IV genome could effectively inhibit virus replication in HEK293 cells. Moreover, our results demonstrated that prophylactic treatment with AdC68 expressing amiRNAs directed against M1, M2 or NP genes of influenza virus completely protected mice from homologous A/PR8 virus challenge and partially protected the mice from heterologous influenza A virus strains such as H9N2 and H5N1. Collectively, our data demonstrate that amiRNAs targeting the conserved regions of influenza A virus delivered by Ad vectors should be pursued as a novel strategy for prophylaxis of influenza virus infection in humans and animals.
