Orally delivered siRNA targeting macrophage Map4k4 suppresses systemic inflammation

Myriam Aouadi, Gregory J. Tesz, Sarah M. Nicoloro, Mengxi Wang, My Chouinard, Ernesto Soto, Gary R. Ostroff () and Michael P. Czech ()
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Myriam Aouadi: Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA
Gregory J. Tesz: Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA
Sarah M. Nicoloro: Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA
Mengxi Wang: Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA
My Chouinard: Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA
Ernesto Soto: Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA
Gary R. Ostroff: Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA
Michael P. Czech: Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA

Nature, 2009, vol. 458, issue 7242, 1180-1184

Abstract: Special delivery for siRNAs The therapeutic potential of gene silencing with siRNAs (short interfering RNAs) is great — in theory. In practice many obstacles will need to be overcome before it becomes a practical proposition, and one of those is the safe delivery of the siRNA to its target tissue. A new delivery system described in this issue may prove to be a significant step towards that end. siRNAs designed to silence expression of the enzyme MAP4k4 in macrophages were encapsulated in micrometre-sized β1,3-D-glucan particles and administered orally to mice. The encapsulated siRNA increased survival rates in mice with lipopolysaccharide-induced inflammation — a common model for inflammatory diseases — and suppressed systemic inflammation. The method is up to 250 times more potent in vivo than previously reported forms of systemic siRNA delivery.

Date: 2009
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DOI: 10.1038/nature07774

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