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Follow on Google News | Previous Claims of siRNA Therapeutic Effects Called into Question by Report in Human Gene TherapyMany 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.
Previous Claims of siRNA Therapeutic Effects Called into Question by Report in Human Gene Therapy New Rochelle, NY—The 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 http://www.liebertpub.com/ 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,” 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 model of influenza, the authors demonstrated that the anti-viral activity of siRNA is mainly due to non-specific stimulation of the immune system rather than to a targeted attack on the disease-causing virus. “siRNA holds tremendous potential as a research tool, however its clinical development is still in its infancy. The study by Robbins et al. points out a very important issue regarding non-specific effects that should be considered when designing and evaluating siRNA strategies,” Human Gene Therapy, the Official Journal of the European Society of Gene and Cell Therapy (www.esgct.org) Mary Ann Liebert, Inc (http://www.liebertpub.com) is a privately held, fully integrated media company known for establishing authoritative peer-reviewed journals in many promising areas of science and biomedical research, including Tissue Engineering, Stem Cells and Development, and Cloning and Stem Cells. Its biotechnology trade magazine, Genetic Engineering & Biotechnology News (GEN), was the first in its field and is today the industry’s most widely read publication worldwide. A complete list of the firm’s 60 journals, books, and newsmagazines is available at www.liebertpub.com Mary Ann Liebert, Inc. 140 Huguenot St., New Rochelle, NY 10801-5215 www.liebertpub.com # # # Mary Ann Liebert, Inc (www.liebertpub.com) End
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