腺病毒介导的RNA干扰策略抗流感病毒感染

项目名称： 腺病毒介导的RNA干扰策略抗流感病毒感染

项目编号： No.31200698

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 免疫学

项目作者： 张洪波

作者单位： 中国科学院上海生命科学研究院

项目金额： 20万元

中文摘要： 流感对人类的公共健康构成严重威胁，每年在全球范围内造成数百万严重病例和50多万人死亡。目前尚无特效的治疗药物，常用的疫苗也只有60-80%的保护率。RNAi由于可以特异性地抑制基因表达, 近年来越来越多地应用于抗病毒治疗或预防的研究。在本项目中，我们设计分别针对流感病毒保守基因NP，M1，M2的microRNA，合成后克隆至pCDNA6.2TM-GW/miR载体，转染细胞，在细胞水平筛选出可有效抑制流感病毒复制的microRNA。然后，将筛选获得的microRNA克隆至黑猩猩型腺病毒载体AdC68，包装出表达microRNA的重组腺病毒，进一步研究其在体内和体外对多种流感病毒的抑制效果。由于腺病毒载体的高表达与高转导特性,通过本研究的开展，有望获得一种新型广谱型抗流感制剂，为流感的预防和治疗提供新策略。

中文关键词： 流感病毒；microRNA；腺病毒；RNA 干扰；通用疫苗

英文摘要： Influenza virus infection is a major public health problem, causing millions of cases of severe illness and as many as 500,000 deaths each year worldwide. Currently，the licensed inactivated vaccines are 60-80% effective against matched influenza strains. Once infected with influenza virus, there is no specific and effective drug against it. The widespread use of antiviral drugs is limited by concerns about serious side effects and the possible emergence of drug-resistant variants. Given the limitations of current anti-influenza virus strategies, the need for novel strategies for prevention and treatment of influenza virus is urgent. RNA interference (RNAi) is an emerging technology that specifically inhibits gene expression. More and more studies have shown that RNAi could inhibit viral gene expression and protect cells from viral infection. In this regard, RNAi technology holds great promise to inhibit the replication of influenza virus. In this project, we aim to develop a new method against influenza infection based on RNAi and adenovirus delivery system. We designed and synthesized dozens of artificial mricroRNAs (amiRNAs) that target to conserved regions of influenza virus genes such as NP, M1 and M2 respectively, then cloned these amiRNAs into a commercially available pcDNATM6.2-GW/miR vector, respectively

英文关键词： influenza virus；microRNA；Adenovirus；RNAi；Universal vaccine