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Orally delivered siRNA targeting macrophage Map4k4 suppresses systemic inflammation

Author

Listed:
  • 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)

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.

Suggested Citation

  • Myriam Aouadi & Gregory J. Tesz & Sarah M. Nicoloro & Mengxi Wang & My Chouinard & Ernesto Soto & Gary R. Ostroff & Michael P. Czech, 2009. "Orally delivered siRNA targeting macrophage Map4k4 suppresses systemic inflammation," Nature, Nature, vol. 458(7242), pages 1180-1184, April.
    • Handle: RePEc:nat:nature:v:458:y:2009:i:7242:d:10.1038_nature07774
    DOI: 10.1038/nature07774
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