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Mechanism for the in-vivo transport of siRNA
Date:9/17/2007

It all started with flowers: in the nineties of the last century Norwegian researchers discovered that additional copies of a particular gene in petunias inhibited its activity instead of reinforcing it as had been assumed. A few years later it was found that the mechanism is based on the degradation of messenger RNA in the cells. Finally, in the late nineties the Nobel prizewinners Andrew Fire and Craig Mello established the technique of RNA interference, in which double-stranded RNA switches genes off efficiently and specifically. The scientists used the nematode (roundworm) Caenorhabditis elegans to study this. Subsequently, however, considerable problems arose in the attempt to transfer the strategy used by Mello and Fire to vertebrates. In particular the administration of small RNAs, known as siRNAs (small interfering RNAs), in animals proved difficult. Although it was possible to administer siRNAs successfully by using various methods such as high-pressure injections or in conjunction with cholesterol, the underlying mechanisms remained obscure. Markus Stoffel, ETH Zurich Professor at the Institute for Molecular Systems Biology, together with chemists from the Alnylam Company, has now succeeded in elucidating the mechanism for the uptake of siRNA in combination with fatty acids in mammals. The corresponding paper, which has just been published in the scientific journal Nature Biotechnology and will also adorn the title page of the printed version in October, represents the basis for possible siRNA therapies, among other things. This is because Stoffel showed that siRNA can be coupled effectively to various fatty acids.

Cholesterol transporters also play a part

Stoffel and his team turned to chemically modified siRNAs in combination with cholesterol, not because the method based on this compound was particularly efficient but because it had the least side-effects. First of all the researchers wanted to know whether siRNA was capab
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Contact: Professor Marcus Stoffel
41-446-334-560
Swiss Federal Institute of Technology
Source:Eurekalert

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