RNA interference silences gene expression through short interfering 21–23-mer double-strand RNA segments that guide mRNA degradation in a sequence-specific fashion. Here we report that siRNAs inhibit virus production by targeting the mRNAs for either the HIV-1 cellular receptor CD4, the viral structural Gag protein or green fluorescence protein substituted for the Nef regulatory protein. siRNAs effectively inhibit pre- and/or post-integration infection events in the HIV-1 life cycle. Thus, siRNAs may have potential for therapeutic intervention in HIV-1 and other viral infections.
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We thank V. François-Bongarçon for help and technical assistance; H. Cargill for help with Fig. 6; and J. Doench for helpful discussions and comments. The following reagents were obtained through the AIDS Research and Reference Reagent Program Division of AIDS, NIAID, NIH: HeLaT4+ and T4pMV7 were provided by R. Axel, pR7-GFP was provided by K. Page and M. Feinberg and Magi-CCR5 was provided by J. Overbaugh. This work was supported by grants NIH F32 AI10523 (to C.D.N.), NIH T32-GM07748 (to M.F.M.), NIH AI 35502 (to R.G.C.), NIH AI 45306 (to P.S.) and NIH MERIT grant R37-GM34277, NCI grant PO1-CA42063 and partially by NCI Cancer Center Support (Core) grant P30-CA14051 (to P.A.S.).
The authors of this paper have applied for a patent that will be owned by the Massachusetts Institute of Technology. It is possible that in the future the authors will receive royalties from this patent.
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Novina, C., Murray, M., Dykxhoorn, D. et al. siRNA-directed inhibition of HIV-1 infection. Nat Med 8, 681–686 (2002). https://doi.org/10.1038/nm725
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