RNA-i: Discovered in a petunia, found in flies and now causing a medical revolution

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The Independent Online

There is barely an area of biomedical science that has not been touched by the revolutionary technique of RNA-interference (RNA-i), an area of research which won last year's Nobel Prize in medicine because of its importance in modern molecular biology.

RNA-i allows scientists to target a gene with exquisite accuracy by giving them a precise molecular tool for gradually turning down a gene's activity, much like a dimmer switch of an electric light bulb.

RNA-i seems to be one of nature's ways of controlling gene activity and it appears to be ubiquitous among all living cells. Scientists discovered RNA-i in petunia plants in the 1990s, but have since found that it occurs in almost every organism studied, from fungi to fruit flies, from mouse to man.

It is possible that the process of controlling gene activity using RNA-i evolved as a primitive form of defence against the lethal genes of invading viruses, before the evolution of sophisticated immune systems in higher animals.

However, it became apparent that scientists could exploit the phenomenon to target specific genes that they wanted to control. For example, they could use it to shut off the vital genes for an invading virus such as HIV - and there are plans for at least one clinical trial to do just that.

Another idea was to use RNA-i to switch off the genes in a human cell that are essential for the growth of a cancer. If these "oncogenes" are turned off or silenced, the cancer should die. Again, clinical trials are being planned.

A further approach is to turn off the genes that are involved in stimulating the growth of new blood vessels. If this can be done in the eye, for instance, you might have a cure for macular degeneration - when new blood-vessel growth blocks vision in the retina.

One other line of research is to use RNA-i to switch off damaged genes responsible for inherited genetic disorders, such as Huntington's disease. Suddenly it was possible to talk about potential cures for previously untreatable illnesses.

There appears to be no limit to the range of disorders that can be addressed with RNA-i. Now, as the latest study in Nature has shown, the technique may even be used as a method of improving the efficacy and safety of existing - as well as future - anti-cancer drugs.

One of the beauties of the RNA-i approach is that it is relatively easy for scientists to make the necessary drugs. In effect, they are just small strands of the RNA molecule, which can be synthesised automatically by machine. Each strand is about 22 units long - tiny compared with the 3 billion units that make up the entire DNA molecule of the human genome.

Each of these "short-interfering" strands of RNA can be targeted specifically to work against a particular gene, which is one of the reasons why the technique is so attractive. It means there is less chance of cross-reactions or unintended side effects.

However, one of the biggest problems with RNA-i is what is called "delivery" - how do you make sure that the synthetic RNA molecules actually get inside the cells that matter? That is the real problem with using RNA-i on patients. Solve that, and you have a potential treatment for many of the most intractable illnesses known to man.

Two American scientists, Andrew Fire and Craig Mello, won the 2006 Nobel Prize in medicine or physiology for their pioneering research into RNA-i, published in 1998. They worked on nematode worms and, some years later, other scientists found that the phenomenon also occurred in human cells - paving the way for clinical treatments for disorders ranging from heart disease to cancer.

In its citation, the Nobel Assembly said RNA-i promised to be one of the most exciting developments in medical science. "RNA interference is already being widely used in basic science as a method to study the function of genes and it may lead to novel therapies in the future," it said.