The Promise

The development of RNA interference (RNAi) into a technology that is poised to revolutionise medicine has been breathtaking. Only 9 years after its discovery in worms by Fire and Mello, the 2006 Nobel Laureates in Physiology and Medicine, in 1998 and the subsequent realisation by Tuschl et al. that so called small interfering RNAs (siRNAs) can induce the same process in human cells in 2001, there are already 5 phase I clinical trials ongoing with many more to enter in the coming years. Scientists and clinicians alike seek to harness the power of RNAi for conditions ranging from age-related macular degeneration, viral infections (RSV, HIV, Hepatitis B and C, pandemic flu etc.), Huntington's Disease to cancer. This is because RNAi allows the specific down-regulation of gene products called mRNAs, and since it is safe to assume that virtually any disease interfaces with a gene regulatory network we should be able to modify, if not cure it by tweaking this network. These networks and the role of individual genes therein are being worked out by thousands of laboratories around the world and has been greatly aided by the sequencing of the human and other genomes and technologies to measure and modify gene activities (among them RNAi itself). As there is consequently no lack of validated gene targets, the main hurdle towards its wide application is thought to be the safe and efficacious delivery of the RNAi inducing agent to the site of disease. Luckily, RNAi can draw from the experience of antisense oligo and gene therapy and the exciting prospect of RNAi has energised some of the best minds to come up with innovative strategies. I will address these and other challenges in the next post before introducing the main players in the RNAi Therapeutics space.

For those who want to understand more about the basic mechanism and discovery of RNAi, a popular documentary can be found at PBS Nova: http://www.pbs.org/wgbh/nova/sciencenow/3210/02.html