Article

Engineering mucosal RNA interference in vivo.

Laboratory of Retrovirology, Division of Infectious Diseases, Department of Medicine, Brown Medical School, 55 Claverick Street, Providence, RI 02903, USA.
Molecular Therapy (impact factor: 6.87). 10/2006; 14(3):336-42. DOI:10.1016/j.ymthe.2006.04.001 pp.336-42
Source: PubMed

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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Keywords

corresponding mRNA levels
 
direct application
 
gateway
 
genetic engineering
 
inflammatory bowel disease
 
liposome-complexed siRNA mediates gene-specific
 
manipulate mucosal gene expression
 
mucosal surfaces
 
murine model
 
nontoxic
 
rectal application
 
relative mucosal resistance
 
RNA interference
 
single vaginal
 
somatic cell gene products