Inhibition of HIV-1 replication by long-term treatment with a chimeric RNA containing shRNA and TAR decoy RNA

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• 作者：Jacob S. Barnor ; Yuichiro Habu ; Norio Yamamoto ; Naoko Miyano-Kurosaki ; Koichi Ishikawa ; Naoki Yamamoto ; Hiroshi Takaku
• 关键词：Chimeric RNA ; siRNA-escape variants ; Virus breakthrough ; Long-term inhibition ; Lentiviral vector
• 刊名：Antiviral Research
• 出版年：2009
• 出版时间：August 2009
• 年：2009
• 卷：83
• 期：2
• 页码：156-164
• 全文大小：1216 K

文摘

Combinatorial therapies for the treatment of HIV-1 infection are effective for reducing patient viral loads and slowing the progression to AIDS. Our strategy was based on an anti-HIV-1 shRNA vector system in which HIV-1 vif-shRNA was fused to a decoy TAR RNA (mini-TAR RNA) to generate vif-shRNA-decoy TAR RNA under the control of the human U6 Pol III promoter. Upon expression in human cells, the RNA molecule was cleaved into its component parts, which inhibited HIV-1 replication in a synergistic manner. This chimeric RNA expressed a dual RNA moiety and greatly enhanced the inhibition of HIV-1 replication under the production of resistant virus by short interference RNA (siRNA) in long-term culture assays. We suggest that this technique provides a practical basis for the application of siRNA-based gene therapy in the treatment of HIV/AIDS.