BioWorld International Correspondent

LONDON - The charity Cancer Research UK launched a £500,000 (US$814,000) research program to use RNA interference technology to systematically uncover the function of all human genes, with the ultimate aim of identifying all genes involved in cancer that would be good drug targets.

The project, a collaboration with the Netherlands Cancer Institute, will use the ability of RNAi to specifically switch off individual genes while leaving others unaffected, one by one, in order to find how they might contribute to the development of cancer.

Paul Nurse, chief executive of Cancer Research UK, said that despite the massive advance represented by sequencing the human genome, the function of most human genes remains unknown. "The next big challenge is to find out exactly what they're all doing, so we can work out which of them are playing important roles in cancer and other diseases.

"Such an endeavor has never before been possible, because dissecting out the function of a single gene from around 35,000 is extremely difficult," he said. "But thanks to the incredible discovery of RNAi, we think we should now be able to crack the problem."

An initial pilot study will look at 300 genes. If successful, the project will be rolled out to cover a further 8,000 or so other genes about which something is known, at a cost of £500,000. The aim is to bring in other partners from the U.S. and Europe.

RNAi is a natural process, discovered in the nematode worm, in which interference RNA is generated that latches onto and disables messenger RNA, preventing generation of specific harmful proteins. The mechanism is thought to be the legacy of an ancient defense against viral infection. It is now known that synthetically produced RNA can be used to turn off target genes in human cells.

Nurse said, "This initiative will push further forward our understanding of the way our genetic information functions in healthy tissue and in disease."

Scientists from Cancer Research UK and the Netherlands Cancer Institute will genetically engineer cells with DNA coding for a specific piece of interference RNA, permanently blocking a particular gene. The library of cells will be available in both organizations, allowing researchers to study the behavior of the cells and how they respond to losing individual genes.

At the same time they will apply interference RNA to cancer cells to try and find the genetic essence of a malignant cell. After bombarding cancer cells with RNAi, the groups will screen for any that have reverted to type and become normal again, thus identifying genes involved in proliferation.

Julian Downward, who will lead the project, said, "Using RNA interference we should be able to find out precisely what we need to take away from a cancerous cell in order to make it normal again. Essentially, we will be dismantling cancer at the level of its genes."

RNAi has been hailed by some as the most important scientific breakthrough of the past decade. Downward said it used to be the case that it took time before the latest technologies filtered down to charities and to academic research laboratories. "It's really exciting to be among the pioneers of the use of RNA interference for cancer research."

In fact, Cancer Research UK holds a key patent on the use of RNAi in mammalian cells, which its technology transfer arm, Cancer Research Technology Ltd., plans to license for a number of applications.