Alnylam and MIT Collaborators Discover Novel "Core-Shell" Nanoparticles for Systemic Delivery of RNAi Therapeutics

CAMBRIDGE, Mass.--(EON: Enhanced Online News)--Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), a leading RNAi therapeutics company, together with collaborators at the Massachusetts Institute of Technology (MIT), announced today the publication of new paper describing discovery of "core-shell" nanoparticles for systemic delivery of RNAi therapeutics. The core-shell nanoparticles were generated using a high-throughput polymer synthesis strategy and screened for intracellular delivery applications including siRNA delivery. These findings, published in the Proceedings of the National Academy of Sciences (Siegwart et al., PNAS, 2011, doi: 10.1073/pnas.1106379108) allow for the development of novel nanoparticles that have optimal chemical and physical properties for effective intracellular delivery of RNAi therapeutics.

"Continued progress in delivery of RNAi therapeutics requires broad-based efforts around novel lipids, conjugates, and polymers. In the current study, core-shell nanoparticles were discovered using combinatorial approaches to identify novel materials for siRNA delivery," said Kevin Fitzgerald, Ph.D., Senior Director of Research at Alnylam. "These findings further expand our systemic delivery platform to achieve the broadest applications of RNAi therapeutics."

"Together with our collaborators at Alnylam, we continue to make exciting progress on delivery of RNAi therapeutics," said Dan Anderson, Ph.D., of the David H. Koch Institute for Integrative Research at MIT. "Importantly, these new data on core-shell nanoparticles highlight non-lipid approaches for siRNA delivery with opportunities for further optimization."

Specifically, this study evaluated a library of over 1,500 chemically diverse nanoparticles as drug delivery vehicles, with precise control over particle size, chemical composition and architecture. The physical and chemical properties of materials can have controlling effects on their utility as nanotherapeutics and the findings revealed that certain chemical functionalities may be advantageous for polymer-based delivery. Initial in vivo studies on one of these novel nanoparticles showed silencing of hepatocyte-specific Factor VII in a pre-clinical model. The ability to control and modify the chemical nature of the core and shell of the nanoparticle may afford utility of these materials in a wide range of drug delivery applications.

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. 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