RNAi is a natural mechanism for silencing specific genes. Genes provide cells with the instructions for making proteins, and proteins—or more specifically proteins made abnormally—are the cause of most human disease. When a gene is silenced, the cell stops making the protein specified by that gene, thereby reducing the occurrence and/or symptoms of disease.
While RNAi was first observed in plants in 1990, the first crucial breakthrough in understanding the RNAi mechanism came from studies in worms. In 1998, the work of Andrew Fire and Craig Mello led to the recognition that long double-stranded RNA (dsRNA) could induce specific gene silencing. Fire and Mello were awarded the Nobel Prize in 2006.
Induction of RNAi using dsRNA quickly became a powerful tool for scientists to study the function of genes in many lower organisms, including worms and fruit flies. However, this approach initially seemed unworkable in mammalian cells, because of the tendency of dsRNA to provoke an immune response and cause cell suicide. Such cell suicide makes biological sense in the true, real-life situation where dsRNA is encountered—namely viral infection—because it aims to prevent replication and spread of the virus to neighboring cells. For a time, however, it was a major obstacle to experimental induction of RNAi in mammalian cells.
This obstacle was overcome by Alnylam scientific founders, who developed a new strategy to trigger RNAi in mammalian cells using relatively small dsRNAs—long enough to induce RNAi, but small enough to avoid inducing an immune response. Alnylam founders were the first to show that smaller dsRNAs, known as “small interfering RNAs” (siRNAs), bind to messenger RNAs (mRNAs) and silence disease causing genes. These discoveries opened the door for application of RNAi as a new therapeutic strategy.
Alnylam was founded in June 2002 with the focus of advancing RNAi therapeutics as a new class of innovative medicines.