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Previous claims of siRNA therapeutic effects called into question by report in human gene therapy
Date:9/2/2008

New Rochelle, NY, September 2, 2008The many recent reports documenting the therapeutic efficacy of short interfering RNAs (siRNAs) in animal models of human disease may actually be describing non-specific therapeutic effects related to the ability of siRNA to activate an immune response, according to a paper in the September 2008 issue (Volume 19, Number 9) of Human Gene Therapy, a peer-reviewed journal published by Mary Ann Liebert, Inc. The paper, which was published "instant online," is available free online at www.liebertpub.com/hum

Marjorie Robbins, Adam Judge, Ellen Ambegia, Catherine Choi, Ed Yaworski, Lorne Palmer, Kevin McClintock, and Ian MacLachaln of Protiva Biotherapeutics (Burnaby, BC Canada), in a paper entitled, "Misinterpreting the Therapeutic Effects of siRNA Caused by Immune Stimulation," emphasize the need for researchers to design siRNA studies that incorporate suitable controls to differentiate the disease-modulating effect of an siRNA from its ability to stimulate an innate immune response.

siRNAs have been highly touted for their ability to target very specifically and selectively the disease-causing factors in a range of disorders, from viral infections to tumors and inflammatory and immunologic processes. However, siRNA also has the potential to activate innate immunity and the production of interferons, which can in turn bring about therapeutic effects in a range of disease models.

The authors of this paper contend that, "surprisingly few of the reported studies have adequately tested, or controlled, for the potential effects of siRNA-mediated immune stimulation."

In the current study, use of a commonly used control siRNA sequence called GFP siRNA, which has only a minimal capacity to activate the immune system, clearly showed the striking difference between the immunostimulatory potential of GFP siRNA and of some other siRNAs. Using a mouse
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Contact: Vicki Cohn
vcohn@liebertpub.com
914-740-2156
Mary Ann Liebert, Inc./Genetic Engineering News
Source:Eurekalert

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