期刊
MOLECULAR THERAPY
卷 14, 期 3, 页码 336-342出版社
CELL PRESS
DOI: 10.1016/j.ymthe.2006.04.001
关键词
RNA interference; microbicide; gene therapy
资金
- NCRR NIH HHS [P20 RR018757, P20 RR017695] Funding Source: Medline
- NIAID NIH HHS [R01 AI058697, P30 AI42853] Funding Source: Medline
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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