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Specific HIV-1 env gene silencing by small interfering RNAs in human peripheral blood mononuclear cells

Gene Therapy volume 10, pages 2046–2050 (2003)Cite this article

Abstract

RNA interference (RNAi) is triggered by the presence of a double-stranded RNA (dsRNA) in the cell, and results in the silencing of homologous gene expression by the specific degradation of an mRNA containing the same sequence. dsRNA-mediated RNAi can be used in a wide variety of eucaryotes to induce the sequence-specific inhibition of gene expression. Synthetic 21–23 nucleotide (nt) small interfering RNAs (siRNAs) with 2-nt 3′ overhangs were recently found to mediate efficient sequence-specific mRNA degradation in mammalian cells. Here, we show that synthetic siRNAs targeted against the viral structural Env proteins encoded by HIV-1 can specifically suppress the expression of HIV-1 genes. The siRNA-mediated RNAi also had advantages over antisense RNA-mediated inhibition, in terms of both the ease of designing effective antiviral agents and their potency. Especially, our best env-specific siRNAs, E7145 targeted to the central region of the V3 loop and E7490 targeted to the CD4 binding site of conserved regions on gp120, significantly inhibited the HIV-1 gene expression. Furthermore, E7145 and E7490 were effective against HIV-1NL4-3 replication in PBMCs for a relatively long time (14 days). Therefore, the use of synthetic siRNAs provides a simple, rapid, and cost-effective tool for new anti-HIV-1 gene therapeutics.

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Acknowledgements

This work was supported in part by a Grant-in-Aid for High Technology Research from the Ministry of Education, Science, Sports, and Culture, Japan, a Grant from the Japan Society for the Promotion of Science in the ‘Research for the Future’ program (JSPS-RFTF97L00593), and a Research Grant from the Human Science Foundation (HIV-K-1031).

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Authors and Affiliations

  1. Department of Industrial Chemistry, Faculty of Engineering, Chiba Institute of Technology, Tsudanuma, Narashino, Chiba, Japan

    W-S Park, M Hayafune, N Miyano-Kurosaki & H Takaku

  2. High Technology Research Center, Chiba Institute of Technology, Tsudanuma, Narashino, Chiba, Japan

    N Miyano-Kurosaki & H Takaku

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  1. W-S Park
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Park, WS., Hayafune, M., Miyano-Kurosaki, N. et al. Specific HIV-1 env gene silencing by small interfering RNAs in human peripheral blood mononuclear cells. Gene Ther 10, 2046–2050 (2003). https://doi.org/10.1038/sj.gt.3302099

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