About RNAi
RNAi 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. RNAi offers the opportunity to harness a natural mechanism to develop specific and potent medicines, and has the potential to become the foundation for a whole new class of therapeutic products.
The discovery of RNAi has been heralded as a major scientific breakthrough that happens only once every decade or so, and represents one of the most promising and rapidly advancing frontiers in biology and drug discovery today. 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. RNAi therapeutics target the 'root' genetic cause of diseases by potently silencing specific messenger RNA, thereby preventing the disease-causing proteins from being made. RNAi therapeutics are a class of oligonucleotide or nucleic acid-based drugs that have the potential to treat disease and help patients in a fundamentally new way.
The discovery of RNA interference
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 of disease.
What later became understood as RNAi was first observed in plants in 1990, but the first crucial breakthrough in understanding the RNAi mechanism came from studies of worms. This came in 1998 with the recognition that long double-stranded RNA (dsRNA) could induce specific gene silencing.
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 prevents 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 the disease causing gene. These discoveries opened the door for application of RNAi as a new therapeutic strategy.
