Gene therapy back on track

US scientists said on Wednesday they found a way around a potential speed bump in the hotly pursued area of genetic therapy known as RNA interference, which has drawn billions of dollars in drug-company investments.

Although one study suggested RNA interference, or RNAi for short, might be toxic, the researchers said they found a safe way to do it.

RNAi burst on the scene a decade ago when US scientists Andrew Fire and Craig Mello showed certain types of RNA could switch off genes that trigger disease, a discovery that earned them the 2006 Nobel Prize in Physiology or Medicine.

RNA stands for ribonucleic acid -- a chemical messenger that is emerging as a key player in the disease process.

Blocking disease-causing genes
Dozens of biotechnology companies are looking for ways to manipulate RNA in order to block genes that produce disease-causing proteins, offering hope for cures to cancer, blindness and Aids.

Those that have shown promise have been snapped up by big drugmakers, such as Merck & Co Inc, which spent $1.1 billion last October to buy Sirna Therapeutics Inc. Since then, other companies, including Pfizer Inc. and AstraZeneca Plc have struck RNAi development deals.

But last year Dr Mark Kay of Stanford University found that a commonly used approach to this technology killed mice, suggesting that it interfered with the normal function of cells.

The study raised fears about whether the toxic effects might be true of different approaches to RNA interference.

"It had the potential to be a significant impediment," said David Bumcrot, a researcher at biotechnology company Alnylam Pharmaceuticals Inc, who led the study.

He and colleagues at the Massachusetts Institute of Technology, reporting in the journal Nature, found a different approach to RNA interference did not have the same toxic effects.

A different approach
While the Kay study used a type of RNA known as small hairpin RNA (shRNA) to disrupt communication to disease-causing genes, Bumcrot and Daniel Anderson of MIT used a method known as small-interfering RNA, or siRNA.

"The approach they used was essentially a gene therapy approach. The RNAi was expressed from a gene that they put into the mice," Bumcrot said in a telephone interview.

"We used a synthetic siRNA, which is delivered directly into the cells," he said.

The research team used a system developed at MIT that delivered RNA directly into the fluid inside cells, where it did not interfere with cell function.

Delivery is key
Bumcrot believes the toxicity in the Stanford study arose from the delivery method. "It was the method and not the mechanism," he said.

They were able to silence 80 percent of the genes they targeted in mice and hamster liver cells without harming the animals.

"It shows siRNA is not toxic," Robert Langer of MIT said in a telephone interview.

"Clearly delivery can make a difference," Langer said. – (Reuters Health)

Read more:
Genetics Centre

September 2007

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