Alnylam Pharmaceuticals, Inc. a leading RNAi therapeutics company, together with collaborators at the Massachusetts Institute of Technology (MIT), announced the publication of new data describing a novel approach for systemic delivery of RNAi therapeutics using synergistic combinations of novel lipid-like materials called “lipidoids.”

“These new data reflect our continued and broad-based commitment to developing novel approaches for the systemic delivery of RNAi therapeutics. In working with world-renowned academic leaders in the field of drug delivery at MIT, we continue to expand our understanding and knowledge about innovative delivery approaches,” said Kevin Fitzgerald, PhD, senior director of Research at Alnylam. “These recently published data show that binary combinations of specific lipidoids can result in optimized lipid nanoparticle formulations with synergistic siRNA delivery properties.”

“Our long-standing collaborative efforts with Alnylam continue to be very productive as evidenced by this current publication, marking the 12th peer-reviewed paper we have co-authored together,” said Dan Anderson, PhD, of the David H Koch Institute for Integrative Research at MIT. “As we continue in these joint efforts, we see boundless opportunities for novel delivery strategies for RNAi therapeutics and we look forward to continued progress.”

The new research results, which were published in the journal Molecular Therapy (Whitehead et al., MolTher, 2011 July 12, doi:10.1038/mt.2011.141), established that binary combinations of lipidoids can be formulated together in a single lipid nanoparticle (LNP) formulation to achieve synergistic gene silencing effects both in vitro and in vivo. In the current study, more than 3,500 novel LNP formulations were prepared and then evaluated for effects on gene silencing. Results demonstrated achievement of synergistic gene silencing when utilizing materials that, when combined, mediated both efficient cellular uptake and productive endosomal escape. The pre-clinical data showed that ineffective single lipidoids could be formulated together to induce robust silencing of the luciferase mRNA in vitro and the Factor VII mRNA in vivo. Importantly, it is anticipated that this binary formulation strategy could be applicable to any siRNA delivery material in any target cell population that utilizes combinations of unique components to mediate distinct steps in the delivery process, for example lipids, polymers, and siRNA conjugates.

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.

Alnylam is a biopharmaceutical company developing novel therapeutics based on RNA interference, or RNAi.