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Inhibition of HCV Replication in HCV Replicon by shRNAs
Authors:Hiroyuki Hamazaki  Hitoshi Takahashi  Kunitada Shimotohno  Naoko Miyano-Kurosaki  Hiroshi Takaku
Institution:1. Department of Life and Environmental Sciences , Chiba Institute of Technology , Chiba, Japan;2. Department of Viral Oncology , Institute for Virus Research, Kyoto University , Kyoto, Japan;3. Department of Life and Environmental Sciences, and High Technology Research Center , Chiba Institute of Technology , Chiba, Japan
Abstract:We show that the vector-derived long dsRNA specifically inhibits the replication of HCV RNA in HCV replicon. We designed a long dsRNA targeted to the full-length HCV IRES/core elements (1-to 377-nt). Our results revealed that the replication of HCV RNA was reduced to near background levels in a sequence-specific manner by the long dsRNAs in the HCV replicon. We also designed four shRNAs against several regions (120- to 139-nt, 260- to 279-nt, 330- to 349-nt, and 340- to 359-nt) of the HCV IRES/Core elements. The two HCV IRES/core-specific shRNAs, 330- to 349-nt and 340- to 359-nt, containing the AUG initiation codon sequence showed stronger HCV inhibitory effects than the other two shRNAs, 120- to 139-nt and 260- to 279-nt.
Keywords:RNAi  Long dsRNA  shRNA  HCV IRES/Core  HCV replicon  Anti-HCV
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