Department of Biotechnology, Beijing Institute of Radiation Medicine, Beijing 100850, China.
Nucleic Acid Ther. 2013 Aug;23(4):244-52. doi: 10.1089/nat.2012.0405. Epub 2013 May 7.
Dengue virus (DENV), a mosquito-borne flavivirus, causes serious diseases and threatens public health in tropical and subtropical areas worldwide. RNA interference (RNAi) is a prevailing strategy for antiviral therapy. In this paper, 6 single artificial microRNAs (amiRNAs) targeting the highly conserved regions of the DENV-2 genome were identified and inhibited virus replication efficiently. Then, effective tandem amiRNAs targeting 2 different DENV-2 genome regions were constructed and expressed simultaneously from a single microRNA-like polycistron to avoid virus variation or mutation escape. Finally, the most high-performance tandem amiRNA was embedded in a lenti-viral vector and inhibited DENV-2 virus replication stably and dose-dependently. Overall, these results indicated that RNAi based on multiple amiRNAs targeting viral conserved regions was an effective approach for improvements of nucleic acid inhibitors of DENV and provided a new therapeutic strategy for DENV infection in humans.
登革热病毒（DENV）是一种蚊媒传播的黄病毒，可导致严重疾病，威胁全球热带和亚热带地区的公众健康。RNA 干扰（RNAi）是一种流行的抗病毒治疗策略。本文中，我们鉴定了 6 种针对 DENV-2 基因组高度保守区域的单个人工 microRNA（amiRNA），它们能有效抑制病毒复制。然后，我们构建了针对 2 个不同 DENV-2 基因组区域的有效串联 amiRNA，并从单个 miRNA 样多顺反子中同时表达，以避免病毒变异或突变逃逸。最后，我们将性能最高的串联 amiRNA 嵌入慢病毒载体中，能够稳定且剂量依赖性地抑制 DENV-2 病毒复制。总的来说，这些结果表明，基于针对病毒保守区域的多个 amiRNA 的 RNAi 是提高 DENV 核酸抑制剂的有效方法，并为人类 DENV 感染提供了新的治疗策略。
