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RNA interference against viruses: strike and counterstrike

Nature Biotechnology volume 25, pages 1435–1443 (2007)Cite this article

Abstract

RNA interference (RNAi) is a conserved sequence-specific, gene-silencing mechanism that is induced by double-stranded RNA. RNAi holds great promise as a novel nucleic acid–based therapeutic against a wide variety of diseases, including cancer, infectious diseases and genetic disorders. Antiviral RNAi strategies have received much attention and several compounds are currently being tested in clinical trials. Although induced RNAi is able to trigger profound and specific inhibition of virus replication, it is becoming clear that RNAi therapeutics are not as straightforward as we had initially hoped. Difficulties concerning toxicity and delivery to the right cells that earlier hampered the development of antisense-based therapeutics may also apply to RNAi. In addition, there are indications that viruses have evolved ways to escape from RNAi. Proper consideration of all of these issues will be necessary in the design of RNAi-based therapeutics for successful clinical intervention of human pathogenic viruses.

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Figure 1: Nucleic acid–based antiviral strategies.
Figure 2: Viral escape strategies from RNAi.

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Acknowledgements

We thank Walter de Vries for critically reading the manuscript and stimulating discussions. RNAi research in the Berkhout laboratory is sponsored by ZonMw (Vici grant and Translational Gene Therapy program), NWO-CW (Top grant), the European Union (LSHP-CT-2006-037301) and the Technology Foundation STW (grant AGT.7708).

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  1. Department of Medical Microbiology, Laboratory of Experimental Virology, Center for Infection and Immunity Amsterdam (CINIMA), Academic Medical Center of the University of Amsterdam, Meibergdreef 15, Amsterdam, 1105, AZ, The Netherlands

    Joost Haasnoot, Ellen M Westerhout & Ben Berkhout

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  1. Joost Haasnoot
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  2. Ellen M Westerhout
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Correspondence to Ben Berkhout.

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Haasnoot, J., Westerhout, E. & Berkhout, B. RNA interference against viruses: strike and counterstrike. Nat Biotechnol 25, 1435–1443 (2007). https://doi.org/10.1038/nbt1369

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