Engineering Mucosal RNA Interference in Vivo

Yingjie Zhang, Patricia Cristofaro, Rebecca Silbermann, Oliver Pusch, Daniel Boden, Tamako Konkin, Virginia Hovanesian, Paul R. Monfils, Murray Resnick, Steven F. Moss, Bharat Ramratnam

Research output: Contribution to journalArticlepeer-review

84 Scopus citations

Abstract

Mucosal surfaces serve as a gateway to disease. Here, we demonstrate that RNA interference can be used to manipulate mucosal gene expression in vivo. Using a murine model, we show that direct application of liposome-complexed siRNA mediates gene-specific silencing in cervicovaginal and rectal mucosa. A single vaginal or rectal administration of siRNA targeting hematopoietic or somatic cell gene products reduced corresponding mRNA levels by up to 90%. Using a murine model of inflammatory bowel disease, we found that the rectal application of siRNA targeting TNF-α led to relative mucosal resistance to experimental colitis. Liposomal siRNA formulations proved nontoxic, did not elicit a nonspecific interferon response, and provide a means for genetic engineering of mucosal surfaces in vivo.

Original languageEnglish (US)
Pages (from-to)336-342
Number of pages7
JournalMolecular Therapy
Volume14
Issue number3
DOIs
StatePublished - Sep 2006
Externally publishedYes

Keywords

  • gene therapy
  • microbicide
  • RNA interference

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Pharmacology
  • Drug Discovery

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