IT HAS been hailed as the greatest medical advance since the discovery of antibiotics. This year we will see if RNA interference lives up to its promise. RNAi, a technique that lets us switch off genes at will, has reached clinical trials and the first results should be in by the end of 2005. If successful, RNAi will herald a new way of treating a host of conditions from cancer and heart disease to viral infections.
RNAi is a natural defence system against viruses that is found across the animal and plant kingdoms. It is triggered when cells encounter the double-stranded fragments of RNA which are the hallmark of some viruses. The cells鈥� molecular machinery uses the fragments to home in on the specific virus genes that encode them and stop those genes from being translated into proteins.
This specificity makes RNAi extremely attractive as a potential therapy, and biotech firms are scrambling to use artificial RNA fragments to target disease-causing genes. The first to reach clinical trials was Acuity Pharmaceuticals, based in Philadelphia, Pennsylvania, which is targeting the eye disease age-related macular degeneration. AMD is the commonest cause of blindness in the west, and is so far incurable. It results from abnormal growth of the blood vessels beneath the retina. In the most severe form of the disease, known as 鈥渨et鈥� AMD, these vessels leak blood and damage the surrounding tissues.
Advertisement
Acuity has designed an RNAi drug dubbed Cand5, which when injected into the eyeball silences the molecular signal that makes these leaky blood vessels grow. 鈥淲e鈥檙e turning off the leak at the source,鈥� says Samuel Reich of Acuity. In tests on monkeys, Cand5 significantly reduced the growth of extra blood vessels after laser injury to the retina, without causing side effects. Now the studies have moved on to human patients. The risk of systemic side effects is low, says Reich, because Cand5 is injected close to the retina rather than into the bloodstream, and it breaks down quickly in the blood.
Other RNAi therapies in the pipeline target cervical cancer, Parkinson鈥檚 disease and high cholesterol levels.
