'Silencing' of genes holds key to fight killer viruses

In the beginning was RNA, the poor relation of its more famous cousin, DNA. The origins of life on Earth four billion years ago are now widely believed to lie in ribonucleic acid rather than its oxygen-challenged cousin, deoxyribonucleic acid.

In the "RNA world" that existed before DNA, all genetic instructions were carried on molecules of ribonucleic acid. When DNA evolved, it proved to be more stable and took over from RNA as the primary gene-carrying substance of life, save for a few RNA viruses.

But RNA still plays a critical role in the vital process of making proteins. One form of RNA acts as a messenger, carrying information locked up in the genetic sequence of the double-stranded DNA in the nucleus of the cell.

Messenger RNA carries this information into the cytoplasm outside the nucleus, where the protein factories of the cell churn out their life-giving products. On these molecules of messenger RNA, the remarkable phenomenon known as RNA interference works.

Genes can be turned off directly by a complicated process within the cell nucleus. This is essential for normal development because most genes, at some point in the development of an organism, have to be turned on and then, at another critical point, turned off.

Some cancers are known to be caused by genes turned on or off at the wrong time. All this was thought to be the preserve of the cell nucleus. But RNA interference (RNAi) has shown that a gene-switching or "silencing" process can also work outside, in the cytoplasm.

The process is rather like a printing press that turns out thousands of copies of several different kinds of magazine. If people had to stopped from reading all the printed copies of just one of these magazines, RNAi is analogous to pulping every copy of that magazine at the newsagents – leaving all other magazines alone – rather than risk interfering with the whole printing process at the point of the central press.

By adding double-stranded RNA to a cell, scientists have found that they can attack and destroy the messenger RNA of a particular gene outside the nucleus. That way, the information of the gene – the genetic recipe for a particular protein – never gets "read". It never gets converted into a protein.

The short strands of RNA that do this are highly specific. One alteration in a single chemical base in its genetic sequence stops it working. They are non-toxic and can be used to switch off any known gene, whether it is a gene for cancer or a gene needed for a virus to replicate.

Until now there have been only two ways of fighting viruses, by vaccines or by drugs known as antivirals, which are highly toxic. Attacking viruses by RNAi is a "significant new strategy", says Gordon Carmichael of the University of Connecticut in Farmington. It also promises to be non-toxic as a natural process used by organisms for billions of years.

RNAi would also become a vital tool in understanding the human genome, said Tom Luschl from the Max Planck Institute for Biophysical Chemistry in Gottingen. "It will dramatically accelerate the biochemical understanding of gene function."