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The promises and pitfalls of RNA-interference-based therapeutics

Abstract

The discovery that gene expression can be controlled by the Watson–Crick base-pairing of small RNAs with messenger RNAs containing complementary sequence — a process known as RNA interference — has markedly advanced our understanding of eukaryotic gene regulation and function. The ability of short RNA sequences to modulate gene expression has provided a powerful tool with which to study gene function and is set to revolutionize the treatment of disease. Remarkably, despite being just one decade from its discovery, the phenomenon is already being used therapeutically in human clinical trials, and biotechnology companies that focus on RNA-interference-based therapeutics are already publicly traded.

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Figure 1: Mechanisms of cellular gene silencing.
Figure 2: In vivo delivery strategies for therapeutic siRNAs.

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Acknowledgements

I thank the National Institutes of Health for grant assistance.

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J.J.R. is a cofounder, and chairman of the scientific advisory board, of Dicerna Pharmaceuticals (Watertown, Massachusetts), which is developing RNAi-based therapeutics. He is also a cofounder of Calando Pharmaceuticals (Pasadena, California), which is developing delivery vehicles for siRNAs, and a scientific adviser for Benitec (Melbourne, Australia), which is developing methodologies for expressing small RNAs.

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Correspondence should be addressed to J.J.R. (jrossi@coh.org).

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Castanotto, D., Rossi, J. The promises and pitfalls of RNA-interference-based therapeutics. Nature 457, 426–433 (2009). https://doi.org/10.1038/nature07758

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