Engineering mucosal RNA interference in vivo.
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.
Zhang
Yingjie
Y
Laboratory of Retrovirology, Division of Infectious Diseases, Department of Medicine, Brown Medical School, 55 Claverick Street, Providence, RI 02903, USA.
Cristofaro
Patricia
P
Silbermann
Rebecca
R
Pusch
Oliver
O
Boden
Daniel
D
Konkin
Tamako
T
Hovanesian
Virginia
V
Monfils
Paul R
PR
Resnick
Murray
M
Moss
Steven F
SF
Ramratnam
Bharat
B
D000818:Animals; D002584:Cervix Uteri / Q000378:metabolism; D005260:Female; D015870:Gene Expression / Q000187:drug effects*; D015316:Genetic Therapy / Q000379:methods*; D015212:Inflammatory Bowel Diseases / Q000628:therapy; D008081:Liposomes; D051379:Mice; D008810:Mice, Inbred C57BL; D009092:Mucous Membrane / Q000378:metabolism; D034622:RNA Interference; D012333:RNA, Messenger / Q000032:analysis / Q000037:antagonists & inhibitors*; D034741:RNA, Small Interfering / Q000008:administration & dosage*; D012007:Rectum / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000235:genetics; D014621:Vagina / Q000378:metabolism
D008081:Liposomes; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D014409:Tumor Necrosis Factor-alpha