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Alnylam Scientists and Collaborators Publish New Article in Nature Describing Discovery of Central Gene in Mitochondrial Physiology

– Research Study Employed an Integrative Genomics Approach Enabled with RNAi Technology –

CAMBRIDGE, Mass.--(BUSINESS WIRE)--Jun 19, 2011 - Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), a leading RNAi therapeutics company, and collaborators at Massachusetts General Hospital (MGH), the Broad Institute, and the David H. Koch Institute for Integrative Cancer Research at the Massachusetts Institute of Technology (MIT), today announced new findings published in Nature (Baughman et al., Nature advance online publication 19 June 2011; doi: 10.1038/nature10234). Using an “integrative genomics” strategy that included RNAi technology, the study identified for the first time the mitochondrial calcium uniporter (MCU), which regulates calcium transport into mitochondria. This new discovery now enables molecular studies on mitochondrial calcium physiology with implications for advancement of new medicines across a broad range of diseases.

“Our approach combined genomics, physiology, biochemistry, and pharmacology to firmly establish MCU as the essential protein component of the mitochondrial calcium uniporter. The molecular identity of this channel has been a mystery for 50 years. Its identification establishes a foundation for studying calcium transport in mitochondria in health and in disease,” said Vamsi Mootha, M.D., Associate Professor of Systems Biology at Harvard Medical School and Investigator at MGH Center for Human Genetic Research. “Use of highly potent in vivo RNAi technology from our collaborators at Alnylam was central to the success of this project.”

“We are excited to continue to work with our colleagues in leading academic laboratories to advance in vivo RNAi technologies for the discovery and molecular validation of target genes involved in physiology and disease. We are pleased to have participated in this landmark study, which demonstrates again the power of Alnylam in vivo RNAi technologies for functional genomics,” said Victor Kotelianski, M.D., Ph.D., D.Sc., Senior Vice President, Distinguished Alnylam Fellow. “The discovery of MCU will enable molecular studies in which the channel apparatus is targeted or manipulated, leading to the potential discovery of new medicines.”

Mitochondria are critical organelles in most eukaryotic cells that generate the cell's supply of adenosine triphosphate (ATP) as a source of energy. Calcium transport via the MCU is an essential component of mitochondrial function. Mitochondrial calcium uptake and the MCU are implicated in a range of cellular functions including apoptosis, or programmed cell death, necrosis, energy metabolism, and hormone secretion and action. In the current study, which builds on an approach and observations previously reported by Dr. Mootha and colleagues in an earlier Nature article (Perocchi et al., Nature 467, 291-296 (2010)), small interfering RNA (siRNA) targeting MCU were used in vivo to demonstrate the role of the candidate gene. Specifically, silencing of MCU in vivo with siRNA abrogated mitochondrial calcium uptake, while having no effect on mitochondrial respiration and membrane potential.

About RNA Interference (RNAi)

RNAi (RNA interference) 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 which 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. Small interfering RNAs (siRNAs), the molecules that mediate RNAi and comprise Alnylam's RNAi therapeutic platform, target the cause of diseases by potently silencing specific 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.

About Alnylam Pharmaceuticals

Alnylam is a biopharmaceutical company developing novel therapeutics based on RNA interference, or RNAi. The company is leading the translation of RNAi as a new class of innovative medicines with a core focus on RNAi therapeutics for the treatment of genetically defined diseases, including ALN-TTR for the treatment of transthyretin-mediated amyloidosis (ATTR), ALN-PCS for the treatment of severe hypercholesterolemia, and ALN-HPN for the treatment of refractory anemia. As part of its “Alnylam 5x15TM” strategy, the company expects to have five RNAi therapeutic products for genetically defined diseases in advanced stages of clinical development by the end of 2015. Alnylam has additional partner-based programs in clinical or development stages, including ALN-RSV01 for the treatment of respiratory syncytial virus (RSV) infection, ALN-VSP for the treatment of liver cancers, and ALN-HTT for the treatment of Huntington's disease. The company's leadership position on RNAi therapeutics and intellectual property have enabled it to form major alliances with leading companies including Merck, Medtronic, Novartis, Biogen Idec, Roche, Takeda, Kyowa Hakko Kirin, and Cubist. In addition, Alnylam and Isis co-founded Regulus Therapeutics Inc., a company focused on discovery, development, and commercialization of microRNA therapeutics; Regulus has formed partnerships with GlaxoSmithKline and sanofi-aventis. Alnylam has also formed Alnylam Biotherapeutics, a division of the company focused on the development of RNAi technologies for application in biologics manufacturing, including recombinant proteins and monoclonal antibodies. Alnylam scientists and collaborators have published their research on RNAi therapeutics in over 100 peer-reviewed papers, including many in the world's top scientific journals such as Nature, Nature Medicine, Nature Biotechnology, and Cell. Founded in 2002, Alnylam maintains headquarters in Cambridge, Massachusetts. For more information, please visit

Alnylam Forward-Looking Statements

Various statements in this release concerning Alnylam's future expectations, plans and prospects, including without limitation, statements regarding the potential for molecular studies on mitochondrial calcium physiology, as well as Alnylam's expectations regarding its “Alnylam 5x15” product strategy, constitute forward-looking statements for the purposes of the safe harbor provisions under The Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by these forward-looking statements as a result of various important factors, including, without limitation, Alnylam's ability to discover and develop novel drug candidates, successfully demonstrate the efficacy and safety of its drug candidates in human clinical trials, and establish and maintain strategic business alliances and new business initiatives, as well as those risks more fully discussed in the “Risk Factors” section of its most recent quarterly report on Form 10-Q on file with the Securities and Exchange Commission. In addition, any forward-looking statements represent Alnylam's views only as of today and should not be relied upon as representing its views as of any subsequent date. Alnylam does not assume any obligation to update any forward-looking statements.


Contact: Alnylam Pharmaceuticals, Inc.
Cynthia Clayton, 617-551-8207
Senior Director, Investor Relations and Corporate Communications
Amanda Sellers, 202-955-6222 x2597



Posted: June 2011