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Interfering with disease: a progress report on siRNA-based therapeutics

Nature Reviews Drug Discovery volume 6, pages 443–453 (2007)Cite this article

Abstract

RNA interference (RNAi) quietly crept into biological research in the 1990s when unexpected gene-silencing phenomena in plants and flatworms first perplexed scientists. Following the demonstration of RNAi in mammalian cells in 2001, it was quickly realized that this highly specific mechanism of sequence-specific gene silencing might be harnessed to develop a new class of drugs that interfere with disease-causing or disease-promoting genes. Here we discuss the considerations that go into developing RNAi-based therapeutics starting from in vitro lead design and identification, to in vivo pre-clinical drug delivery and testing. We conclude by reviewing the latest clinical experience with RNAi therapeutics.

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Figure 1: Mechanism of RNA interference in mammalian cells.
Figure 2: Turning siRNA into drugs.
Figure 3: Delivery of small interfering RNAs.

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Acknowledgements

The authors would like to thank their collaborators and colleagues for useful discussions. J.L. was supported by NIH grants AI056900 and AI070302.

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Authors and Affiliations

  1. Antonin de Fougerolles and John Maraganore are at Alnylam Pharmaceuticals Inc., 300 Third Street, Cambridge, Massachusetts 02142, USA.,

    Antonin de Fougerolles, Hans-Peter Vornlocher & John Maraganore

  2. Hans-Peter Vornlocher is at Alnylam Europe AG, Fritz-Hornschuch-Str. 9, Kulmbach 95326, Germany.,

    Hans-Peter Vornlocher

  3. Judy Lieberman is at the CBR Institute for Biomedical Research, 200 Longwood Avenue, Boston, Massachusetts 02115, USA.,

    Judy Lieberman

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  1. Antonin de Fougerolles
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  2. Hans-Peter Vornlocher
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Correspondence to Antonin de Fougerolles or Judy Lieberman.

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Competing interests

Antonin de Fougerolles, Hans-Peter Vornlocher and John Maraganore are employees of Alnylam Pharmaceuticals and have financial interests in Alnylam. Judy Lieberman is a member of the Scientific Advisory Board of Alnylam.

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de Fougerolles, A., Vornlocher, HP., Maraganore, J. et al. Interfering with disease: a progress report on siRNA-based therapeutics. Nat Rev Drug Discov 6, 443–453 (2007). https://doi.org/10.1038/nrd2310

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