German researchers have used a novel gene therapy approach to reduce blood cholesterol levels in mice. The research, published in the journal Nature, uses RNA - a close chemical relative of DNA. The scientists, based at biotech firm Alnylam Pharmaceuticals in Kulbach, describe their study as 'a historic step forward' in the development of a new technique called RNAi (RNA interference ). Julian Downward, of Cancer Research UK, said the work 'brings the prospect of uniquely targeted therapies a big step closer'.
RNAi is thought to be a naturally-occurring defence mechanism against viruses, one which scientists are trying to exploit as a way of selectively shutting down gene activity. The approach involves injecting cells with specific pieces of RNA, which then trigger the breakdown of a particular messenger RNA molecule - the intermediate stage between a gene and the protein it codes for. In this way, scientists can selectively shut down production of any protein made by the cell, without affecting any others. However, in practice, it has proved difficult to get these short pieces of RNA into the cells where they are needed.
In the latest study, the researchers used small RNA molecules specific to the mRNA (messenger RNA) for a protein called apoB, which controls blood cholesterol levels. To get the RNA into the cell, they attached cholesterol to the end of the molecule, in the hope that this would 'guide' the RNA into cells that normally deal with this fat. The addition of cholesterol also seems to make the RNA more stable in the body. The team injected the cholesterol-RNA mixture into the blood of mice with high cholesterol levels. The approach worked better than they expected - levels of 'bad' cholesterol dropped by 44 per cent in the treated animals.
John Maraganore, head of Alnylam, says the company now hopes to develop similar methods to treat conditions such as diabetes, obesity and cancer. Other researchers say the technique has removed a major obstacle to developing new treatments based on RNAi. 'This is a fairly simple solution to a problem that could have been immense in this field', said US biologist John Rossi. However, he added that Alnylam still need to address many practical issues before the treatment can be tried in humans, including the dosage, how often it would be required, and the best way of delivering the drug.
Sources and References
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RNA treatment lowers cholesterol
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Huge potential for gene therapy
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Technique for 'turning off' danger genes is used to cut cholesterol
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Unlikely ally rescues gene-blocking therapy
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