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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
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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-alpha 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.

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AnimalsCervix UteriFemaleGene ExpressionGenetic TherapyInflammatory Bowel DiseasesLiposomesMiceMice, Inbred C57BLMucous MembraneRNA InterferenceRNA, MessengerRNA, Small InterferingRectumTumor Necrosis Factor-alphaVaginaJournal ArticleResearch Support, N.I.H., Extramural

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Yingjie Zhang, Patricia Cristofaro, Rebecca Silbermann, Oliver Pusch, Daniel Boden, Tamako Konkin, Virginia Hovanesian, Paul R Monfils, Murray Resnick, Steven F Moss, Bharat Ramratnam. 2006-06-12. Engineering mucosal RNA interference in vivo.. https://doi.org/10.1016/j.ymthe.2006.04.001

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