Alnylam and Collaborators Publish New Paper in the Journal Nature on the In Vivo Efficacy and Safety of RNAi Therapeutics
Sep 26, 2007 13:41:01 (ET)
CAMBRIDGE, Mass., Sep 26, 2007 (BUSINESS WIRE) -- Alnylam Pharmaceuticals, Inc. (ALNY, Trade ), a leading RNAi therapeutics company, today announced the publication of a key study in the journal Nature by Alnylam and scientists at Roche Kulmbach, together with collaborators from the Swiss Federal Institute of Technology (ETH), UT Southwestern Medical Center at Dallas, and the Massachusetts Institute of Technology (MIT). In the study, acute and repeated dosing of small interfering RNAs (siRNAs), the molecules that mediate RNAi, was found to achieve specific and robust silencing of target genes in vivo without any disruption of the endogenous microRNA pathway.
"An important question in the advancement of RNAi therapeutics has been the relationship between silencing target genes with siRNAs and the potential consequences for the normal regulatory role of microRNAs expressed in the same cells and tissues. Our study published in Nature demonstrates the ability to clearly dissociate siRNA-mediated gene silencing effects from cellular processes related to microRNA biosynthesis and function in vivo," said Victor Kotelianski, M.D., Ph.D., Vice President for Research at Alnylam. "This new study continues to extend Alnylam's scientific leadership in the field of RNAi research and represents an important de-risking event towards the translation of the technology into innovative medicines."
"RNAi therapeutics hold great promise as an approach to create a whole new class of innovative medicines," said Hans-Peter Vornlocher, Ph.D., Vice President of Research at Roche Kulmbach, a wholly owned subsidiary of Roche. "This new study highlights the potential of achieving the desired pharmacologic effects for siRNAs without undesired interruption of endogenous microRNAs. Performing such studies in vivo with technologies developed by Alnylam, Roche Kulmbach, and collaborators greatly strengthens the importance of these findings for further advancement of RNAi therapeutics."
Previously, scientists from Stanford had published findings related to the toxicities associated with short hairpin RNAs (shRNAs) expressed from viral vectors in a gene therapy application of RNAi (Grimm et al., Nature 441, 537-41 (2006)). In the new study (John et al., Nature advance online publication, 26 September 2007 (DOI:10.1038/nature06179), Alnylam scientists and collaborators demonstrated the ability of synthetic siRNAs to silence three distinct hepatocyte-expressed genes -- apolipoprotein B, factor VII, and SREBP cleavage-activating protein, or "SCAP" -- to levels of greater than 80 percent with both single dose and repeat dose administration of target-specific siRNAs in mice or hamsters. These RNAi-mediated gene silencing effects were well tolerated and were not associated with detectable perturbations in the biosynthesis or function of certain hepatocyte-expressed microRNAs and were not found to induce off-target effects. Thus, acute and chronic dosing with siRNAs were found to achieve desired levels of efficacy without observed toxicologic effects related to the microRNA pathway.
About RNA Interference (RNAi)
RNAi is a revolution in biology, representing a breakthrough in understanding how genes are turned on and off in cells, and a completely new approach to drug discovery and development. Its discovery has been heralded as "a major scientific breakthrough that happens once every decade or so," and represents one of the most promising and rapidly advancing frontiers in biology and drug discovery today, and was awarded the 2006 Nobel Prize for Physiology or Medicine. RNAi is a natural process of gene silencing that occurs in organisms ranging from plants to mammals. By harnessing the natural biological process of RNAi occurring in our cells, the creation of a major new class of medicines, known as RNAi therapeutics, is on the horizon. RNAi therapeutics target the cause of diseases by potently silencing specific messenger RNAs (mRNAs), thereby preventing disease-causing proteins from being made. RNAi therapeutics have the potential to treat disease and help patients in a fundamentally new way.
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