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A study in the 25 May issue of Nature (Vol. 441, No. 7092, pp. 537-541) shows the yellow card to the use of RNA interference in medicine. Mark Kay and his colleagues show that the long-term expression of RNA fragments in mice can end up killing the animals.
In RNA interference, a tiny piece of RNA is added to cells and used to switch off a particular gene; there is great hope that this strategy could be used to treat human disease. The researchers show that a virus can deliver so-called 'short hairpin RNAs' (shRNAs) to mouse liver cells. But of the 49 shRNAs they delivered, 36 of them caused liver injury - with 23 ultimately causing death. The researchers found that the shRNAs interfered with the function of endogenous liver microRNAs, probably by competing for a limited supply of certain cellular proteins required for processing small RNAs. On the positive side, the group also show that delivering weak doses of one shRNA molecule can combat hepatitis B virus, suggesting that the technique could still work if the RNA dose is carefully controlled. CONTACT Mark M A Kay (Stanford University, Stanford, CA, USA)
E-mail: markay@stanford.edu (C) Nature press release.
Message posted by: Trevor M. D'Souza
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