RNAi (RNA interference) is a revolution in biology – a breakthrough in understanding how genes are turned on and off in cells – and, represents a completely new approach to drug discovery and development. The importance of its discovery was recognized by the award of the 2006 Nobel Prize for Physiology or Medicine, and RNAi has been heralded as “a major scientific breakthrough that happens once every decade or so.” It is widely considered one of the most promising and rapidly advancing frontiers in biology and drug development today.
RNAi is a natural mechanism of gene silencing that occurs in organisms ranging from plants to mammals. The genetic material, DNA, contains genes that provide cells with the instructions for making specific proteins, which are essential for the existence of the organism, but could also be involved in disease.
Proteins are made from DNA through a number of steps, including transcription from DNA to messenger RNA (mRNA) and translation of mRNA to protein. Small interfering RNA (siRNA), the molecules that mediate RNAi and comprise Alnylam’s RNAi therapeutic platform, target the cause of diseases by potently silencing specific mRNA, thereby preventing disease-causing proteins from being made. Because siRNA molecules target mRNA and not DNA, the effects of RNAi are not permanent. Based on their mechanism of action, we believe RNAi therapeutics have the potential to treat disease and help patients in a fundamentally new way. RNAi therapeutics have been demonstrated to specifically silence genes in animal models of human disease and as well as in several human clinical studies.
As with other major biological discoveries, such as recombinant DNA and monoclonal antibodies, the fact that RNAi is a natural biological pathway lead many to believe that it could become a particularly safe and effective therapeutic platform. RNAi is also widely exploited by researchers and drug developers for biological research and drug target validation. It is therefore not surprising that there is a great deal of interest in using RNAi as a therapeutic modality itself.
The majority of drugs today, such as small molecules and monoclonal antibodies, are designed to inactivate proteins by directly binding, while not eliminating them. Much of the interest in RNAi is based on the fact that the RNAi mechanism operates upstream of protein production by silencing the mRNA that codes for such proteins, thereby preventing the disease-causing proteins from being made in the first place. By way of analogy, the RNAi approach is akin to “stopping a flood by turning off the faucet” as compared with today’s medicines that simply “mop up the floor.”