Gene silencing prevents its first human disease

The discovery over a decade ago that snippets of RNA can be used as gene silencers in worms garnered a Nobel prize in 2006. Now, for the first time, RNA interference (RNAi) has been proven effective against a human disease – a common respiratory virus.

Under RNAi, short strands of RNA are added to cells to destroy any native RNA molecules with a complementary sequence of letters. Since genes use RNA molecules to make proteins, these snippets effectively "silence" genes that carry the same sequence. In animals, RNAi has shown promise, but progress in people has been slow.

John DeVincenzo studies paediatric infectious disease at the University of Tennessee Health Science Center in Memphis. He and his colleagues tested the ability of short interfering RNA (siRNA) to inhibit viruses of the respiratory tract, where cells are exceptionally willing to take up RNA snippets.

Eighty-five healthy adults were given a nasal spray containing either a placebo or siRNA designed to silence one of the genes of respiratory syncytial virus (RSV), which is the leading cause of infant hospitalisation in the US but fairly harmless in healthy adults.

Delivery issue

They were to use the spray daily for five days. On day two, all the volunteers were infected with live RSV. By day 11, just 44 per cent of those who received the RNAi nasal spray had RSV infections, compared with 71 per cent of the placebo group.

RNAi can trigger an immune response, which might have helped keep infections at bay. But blood samples showed that the risk of RSV infection did not depend on levels of immune molecules, suggesting that RNAi's protective effect was due to the silencing of genes.

The team is now testing the therapy in lung-transplant patients, who take immunity-suppressing drugs that can make RSV infections deadly. DeVincenzo also hopes to test the therapy in infants soon.

For non-respiratory diseases, however, new ways of getting RNA into the target cells are still needed. "Delivery has always been the big issue for RNAi," says John Rossi, a molecular geneticist at City of Hope medical centre in Duarte, California, who is testing RNAi's potential to fight HIV.

Journal reference: Proceedings of the National Academy of Sciences, DOI: 10.1073/pnas.0912186107

via Gene silencing prevents its first human disease - health - 26 April 2010 - New Scientist.