Alnylam is strategically focused on developing and commercializing novel double-stranded RNA therapeutics based on the natural process of RNAi which encompasses both miRNA and short interfering RNA (siRNA), as the basis for a whole new class of therapeutic products to treat a wide range of human diseases.
In October 2004, Alnylam and Isis Pharmaceuticals co-exclusively licensed certain core intellectual property relating to all therapeutic uses of microRNA from the Max Planck Society granting the rights to patent applications based on the microRNA work of Dr. Thomas Tuschl, a leading scientist in early siRNA research and one of the founders of Alnylam. During his research efforts, Dr. Tuschl discovered more than 100 naturally occurring micro-RNAs that are present in mammalian cells. These microRNAs have the potential to be new drug targets or therapeutic products and are the subjects of the licensed patent applications.
What is microRNA?
RNAi can also be induced by microRNAs, or miRNAs, that occur naturally within all mammalian cells. The miRNA molecules are encoded by the cell's own genes, giving rise to small stretches of RNA that exist as double-stranded molecules similar to siRNAs. There are at least 250 miRNA genes in the human genome, and they are thought to work through RNAi to regulate the activity of an estimated one-third of genes in the genome. The inappropriate absence or presence of specific miRNA molecules in various cells has been shown to be associated with specific human diseases.
Future potential with microRNAs
In October 2005, Alnylam and scientists from Rockefeller University published in the scientific journal Nature a novel approach to regulate gene expression through the silencing of miRNAs (Nature 438, 685-689). The publication describes the rational design of a potential new class of chemically modified RNA-based drugs, called 'antagomirs', that specifically silence miRNAs across multiple tissue types following therapeutically relevant administration in animals. The discovery of antagomirs represents the first-ever demonstration of pharmacologic strategy to silence miRNAs.
In the Nature paper, Antagomirs demonstrated specific in vivo silencing of the target miRNA in tissues including liver, lung, kidney, heart, and bone marrow. This silencing was shown to be sustained for over 20 days following a single treatment course. Further, efficient silencing of a liver-specific miRNA (miRNA-122) recently shown to be required for hepatitis C infection was achieved without any evidence of adverse effects. Alnylam believes this research creates the opportunity to design antagomirs that target miRNAs in the context of human diseases, such as cancer and viral infection.