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

doi:10.1016/j.ymthe.2006.04.001

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 journal › Article › peer-review

92 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 language	English (US)
Pages (from-to)	336-342
Number of pages	7
Journal	Molecular Therapy
Volume	14
Issue number	3
DOIs	https://doi.org/10.1016/j.ymthe.2006.04.001
State	Published - Sep 2006
Externally published	Yes

Keywords

RNA interference
gene therapy
microbicide

ASJC Scopus subject areas

Molecular Medicine
Molecular Biology
Genetics
Pharmacology
Drug Discovery

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10.1016/j.ymthe.2006.04.001

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title = "Engineering Mucosal RNA Interference in Vivo",

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.",

keywords = "RNA interference, gene therapy, microbicide",

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

note = "Funding Information: This work was supported by a Career Development Grant and R01AI058697 from NIAID/NIH (B.R.), the Center for Cancer Research Development (NIHP20RR017695), and the Roger Williams Medical Center COBRE (NIHP20RR018757). This research has been facilitated by the infrastructure and resources provided by the Lifespan/Tufts/Brown Center for AIDS Research (NIHP30 AI42853). ",

year = "2006",

month = sep,

doi = "10.1016/j.ymthe.2006.04.001",

language = "English (US)",

volume = "14",

pages = "336--342",

journal = "Molecular Therapy",

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T1 - Engineering Mucosal RNA Interference in Vivo

AU - Zhang, Yingjie

AU - Cristofaro, Patricia

AU - Silbermann, Rebecca

AU - Pusch, Oliver

AU - Boden, Daniel

AU - Konkin, Tamako

AU - Hovanesian, Virginia

AU - Monfils, Paul R.

AU - Resnick, Murray

AU - Moss, Steven F.

AU - Ramratnam, Bharat

N1 - Funding Information: This work was supported by a Career Development Grant and R01AI058697 from NIAID/NIH (B.R.), the Center for Cancer Research Development (NIHP20RR017695), and the Roger Williams Medical Center COBRE (NIHP20RR018757). This research has been facilitated by the infrastructure and resources provided by the Lifespan/Tufts/Brown Center for AIDS Research (NIHP30 AI42853).

PY - 2006/9

Y1 - 2006/9

N2 - 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.

AB - 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.

KW - RNA interference

KW - gene therapy

KW - microbicide

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JO - Molecular Therapy

JF - Molecular Therapy

IS - 3

ER -

Engineering Mucosal RNA Interference in Vivo

Abstract

Keywords

ASJC Scopus subject areas

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