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Activation of the mammalian immune system by siRNAs

Abstract

Inhibition of gene expression through RNA interference (RNAi) is emerging as a powerful experimental tool for gene function and target validation studies. The potential uses of this technology seem unlimited, extending to the prevention and therapy of human diseases. However, recent work demonstrating that there are unanticipated, different nonspecific effects associated with the use of small interfering RNAs in mammals has raised concerns about the safe use of RNAi in vivo. These nonspecific effects include activation of the immune system, potentially harming the individual. The application of screening assays for nonspecific activation of both innate and acquired immunity will be necessary for further development of RNAi as a therapeutic tool.

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Figure 1: Pathways involved in the recognition of siRNAs by the mammalian immune system.

Renee Lucas

Figure 2: Pathways activated by siRNAs in mammalian cells.

Renee Lucas

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Acknowledgements

We would like to thank Patricia Stanhope-Baker, Anthony Sadler, Mark Whitmore and Michelle Holko for helpful discussion and suggestions. Work in the Williams laboratory is supported by National Institutes of Health grants RO1 AI34039 and PO1 CA 62220.

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Correspondence to Bryan R G Williams.

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Marques, J., Williams, B. Activation of the mammalian immune system by siRNAs. Nat Biotechnol 23, 1399–1405 (2005). https://doi.org/10.1038/nbt1161

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