Previous Claims of siRNA Therapeutic Effects Called into Question by Report in 'Human...

Previous Claims of siRNA Therapeutic Effects Called into Question by Report in
'Human Gene Therapy'

NEW ROCHELLE, N.Y., Sept. 2 /PRNewswire/ -- 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 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, BCCanada), 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 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," says James M. Wilson, MD,
PhD, Editor-in-Chief, and Head of the Gene Therapy Program, Division of
Medical Genetics, University of Pennsylvania School of Medicine, in
Philadelphia.
'Human Gene Therapy,' the Official Journal of the European Society of Gene
and Cell Therapy (www.esgct.org), the British Society for Gene Therapy
(www.bsgt.org), and the French Society of Cell and Gene Therapy
(www.sftcg.fr), is an authoritative peer-reviewed journal published monthly in
print and online that presents reports on the transfer and expression of genes
in mammals, including humans. Related topics include improvements in vector
development, delivery systems, and animal models, particularly in the areas of
cancer, heart disease, viral disease, genetic disease, and neurological
disease, as well as ethical, legal, and regulatory issues related to the gene
transfer in humans. Tables of contents and a free sample issue may be viewed
online at www.liebertpub.com
Mary Ann Liebert, Inc (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
Contact: Vicki Cohn, Mary Ann Liebert, Inc, (914) 740-2100, ext. 2156,
vcohn@liebertpub.com
SOURCE Mary Ann Liebert, Inc

Vicki Cohn, Mary Ann Liebert, Inc, +1-914-740-2100, ext. 2156,
vcohn@liebertpub.com