Gene-based therapy for blindness?

The first clinical trial based on a promising new technology called RNAi (RNA interference) is set to begin in the US, to treat a progressive eye disorder. The researchers hope to test the safety of the technique for treating a disease called wet age-related macular degeneration (AMD). This condition, which is the leading cause of adult blindness in the developed world, is caused by the abnormal growth of blood vessels behind the retina. The Food and Drug Administration (FDA) last week granted permission to biotech firm Acuity Pharmaceuticals to start the phase I trial later this year.

The symptoms of AMD appear when the abnormal blood vessels leak blood and fluid, damaging light-sensitive cells in the retina. The new trial aims to test the safety of a new treatment for this condition, which involves injecting RNA (a chemical relative of DNA) molecules directly into the patients' eyeballs. The scientists hope that this will stop the blood vessels growing, by blocking production of a key protein. US RNAi expert Michael McManus, of the University of California in San Francisco, told New Scientist magazine that the planned trial was 'tremendously exciting', adding 'it represents the first step in using this technology to treat a human disease'.

RNAi is thought to be a naturally-occurring defence mechanism against viruses, which is now being exploited as a way of selectively shutting down gene activity. It involves injecting cells with short, specific pieces of RNA, which then trigger the breakdown of a particular messenger RNA molecule - the intermediate stage between a gene and the protein it codes for. In this way, scientists can selectively shut down production of any protein made by the cell, without affecting any others.

As well being a crucial new research tool for working out what newly-identified genes and proteins do, RNAi could potentially lead to new treatments for a range of diseases caused by overproduction of a particular protein, or production of a faulty protein. In the AMD trial, researchers will inject many copies of an RNA molecule called Cand5 into the eye, which they hope will switch off production of a protein called vascular endothelial growth factor (VEGF). The cells lining the back of the eye should absorb the Cand5 RNAs, shutting down VEGF production, which in turn should stop growth of the blood vessels. Samuel Reich, of Acuity, says that in contrast to previous treatments for AMD aiming to block the action of VEGF, which 'act like a mop in a leaky basement', RNAi 'turns off the leak at the faucet'.