Inhibition of HIV-1 replication by long-term treatment with a chimeric RNA containing shRNA and TAR decoy RNA.
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.
Barnor
Jacob S
JS
Department of Life and Environmental Science, Chiba Institute of Technology, Narashino, Chiba, Japan.
Habu
Yuichiro
Y
Yamamoto
Norio
N
Miyano-Kurosaki
Naoko
N
Ishikawa
Koichi
K
Yamamoto
Naoki
N
Takaku
Hiroshi
H
D019380:Anti-HIV Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D016325:HIV Long Terminal Repeat / Q000187:drug effects; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000821:virology; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics / Q000494:pharmacology*; D014779:Virus Replication / Q000187:drug effects*; D054320:vif Gene Products, Human Immunodeficiency Virus / Q000037:antagonists & inhibitors / Q000235:genetics
D019380:Anti-HIV Agents; D034741:RNA, Small Interfering; D054320:vif Gene Products, Human Immunodeficiency Virus; C514847:vif protein, Human immunodeficiency virus 1