Leading RNAi therapeutics company, Alnylam Pharmaceuticals' scientists have discovered a novel method for monitoring RNAi activity in blood samples, representing a potential major advance for future development of RNAi therapeutics, other therapeutic modalities, and diagnostics.

The new pre-clinical research discovery results were presented at the Keystone Gene Silencing by Small RNAs meeting, being held February 7 – 12, in Vancouver, BC.

This new method is called “circulating extracellular RNA detection” (cERD), allows quantitative measurement of tissue-specific mRNA silencing from biological fluids including blood and cerebrospinal fluid (CSF). Alnylam intends to enable use of the new technology in academic research and license industry to deploy the technology.

“We are very excited about this new discovery by Alnylam scientists on a novel approach for monitoring RNAi activity in blood samples. The cERD method enables routine and frequent measurement of tissue-specific target gene silencing, without the need for invasive tissue biopsies,” said Rachel Meyers, Ph.D., Vice President, Research at Alnylam. “We believe that this approach could be transformative for the development of RNAi therapeutics, in addition to having potential applications with other therapeutic modalities. In this regard, we are pleased to launch our efforts enabling industrial applications with a technology license to Isis.”

New pre-clinical results describing the cERD method demonstrate the ability to quantitatively monitor tissue-specific mRNA modulation in a non-invasive manner. Specifically, the new findings demonstrate that tissue-specific mRNAs can be detected in blood and CSF. Based on analysis of serum samples, mRNAs appear to circulate in blood via exosomes, a newly discovered class of cell-derived particles. The cERD method allows analysis of all circulating RNA, whether or not it is associated with exosomes. Administration of RNAi therapeutics toward the liver-specific target genes transthyretin (TTR) and transmembrane protease, serine 6 (Tmprss6) was found to result in dose-dependent silencing of target genes in both tissue mRNA, as measured in tissue samples, and blood-derived mRNA, as measured by the cERD method.

Both onset and duration of mRNA silencing were found to be closely matched between tissue and blood-derived mRNA. Pre-clinical results were confirmed in a variety of animal models. Further, administration of RNAi therapeutics targeting the alpha-synuclein gene in the central nervous system (CNS) was found to result in silencing of the target gene in both tissue and CSF-derived mRNA, as measured by the cERD method. In addition, the cERD method was successfully applied to monitor activity of microRNA therapeutics and gene therapy vectors. Research on the new cERD method was done in collaboration with Derrick Gibbings at the Swiss Federal Institute of Technology, Zurich.

Alnylam intends to broadly enable academic research and also support industry efforts on RNAi therapeutics and other modalities with the newly described cERD method via a broad-based licensing effort. Alnylam announced that its initial cERD license has been provided to Isis Pharmaceuticals.

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 which was awarded the 2006 Nobel Prize for Physiology or Medicine. It 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.