The silence of the genes
SIROCCO, a recently started EU funded project, is looking into how RNA silencing - the switching off of genes - could be used to treat life threatening diseases. RNA silencing, also called RNA interference, is the cell's natural ability to turn off any of our genes. Up until the 1990s this characteristic of ribonucleic acid (RNA) was unknown to life scientists, who thought they understood all the principles of gene regulation with only the details remaining to be worked out. The discovery of RNA silencing came about by researchers who were attempting to alter the colours of petunias. Since then this gene silencing mechanism has been found to occur in all sorts of organisms, from yeasts to humans. RNA silencing is thought to have evolved as a defence mechanism against viruses. In primitive cells it was a type of immune system that could recognise and then silence viral genes. Later in evolution the silencing mechanism was recruited for switching off genes involved in the normal growth of cells and responses to stress. 'Only a few years ago it was unknown, but now RNA silencing is one of the most powerful tools available to researchers. We can use it to understand the function of genes and the mechanisms of cellular regulation,' said Professor David Baulcombe of the Sainsbury Laboratory at the John Innes Centre, the leading partner in SIROCCO. By introducing specific silencing RNAs into an organism, scientists could in theory programme a molecule to switch off the genes of a virus such as HIV, or even switch off faulty cancer causing genes, leaving healthy genes intact. 'We can [...] use it as a diagnostic tool for cancer and other diseases. In future it may also be possible to use RNA silencing as the basis of novel therapy for diverse diseases ranging from avian influenza to cancer.' Despite rapid progress in understanding RNA silencing, a lot remains to be done before the mechanism can be used to save lives. By bringing together 17 world-class laboratories and companies from nine European countries, the SIROCCO consortium hopes to make significant inroads in the study of this revolutionary technique. 'For example we need to ensure that an RNA targeted against gene X will only silence gene X and nothing else. When we can do that we will be able to use RNA as a drug without side effects. We also need to understand more about the role of silencing RNAs in normal growth and development. That information will then allow us to use the presence of silencing RNAs to diagnose disease states in a cell,' explained Prof Baulcombe.