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RNAi therapeutics: a potential new class of pharmaceutical drugs

Nature Chemical Biology volume 2, pages 711–719 (2006)Cite this article

Abstract

The rapid identification of highly specific and potent drug candidates continues to be a substantial challenge with traditional pharmaceutical approaches. Moreover, many targets have proven to be intractable to traditional small-molecule and protein approaches. Therapeutics based on RNA interference (RNAi) offer a powerful method for rapidly identifying specific and potent inhibitors of disease targets from all molecular classes. Numerous proof-of-concept studies in animal models of human disease demonstrate the broad potential application of RNAi therapeutics. The major challenge for successful drug development is identifying delivery strategies that can be translated to the clinic. With advances in this area and the commencement of multiple clinical trials with RNAi therapeutic candidates, a transformation in modern medicine may soon be realized.

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Figure 1: Cellular mechanism of RNA interference.
Figure 2: Chemical modifications of siRNAs.
Figure 3: Critical nucleotide positions in siRNAs.
Figure 4: Organs for which RNAi proof of concept has been demonstrated.

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Acknowledgements

We thank J. Maraganore and B. Greene for critical reading of the manuscript, M. Duckman for graphics assistance and A. Capobianco for word processing assistance.

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  1. Alnylam Pharmaceuticals, Inc., 300 Third Street, Cambridge, 02142, Massachusetts, USA

    David Bumcrot, Muthiah Manoharan, Victor Koteliansky & Dinah W Y Sah

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  1. David Bumcrot
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Correspondence to Dinah W Y Sah.

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Bumcrot, D., Manoharan, M., Koteliansky, V. et al. RNAi therapeutics: a potential new class of pharmaceutical drugs. Nat Chem Biol 2, 711–719 (2006). https://doi.org/10.1038/nchembio839

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