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Mechanism for the in-vivo transport of siRNA
Date:9/22/2007

he alternative doors be" The ETH Zurich researchers remembered that a gene product Sid1, which is necessary for the cellular uptake of siRNA, occurs in the worm Caenorhabditis elegans. The corresponding gene also has a homologue in mammals. By inactivating it, the scientists showed that it is also necessary in mammals. The overall result from all the discoveries is a mechanism for siRNA administration that starts with the bonding of siRNAs to particular fatty acids. This combination is linked to lipophilic proteins that bring about docking onto the tissue cells. The doors that allow the siRNA-fatty acid molecules to enter are then situated close to the docking station.

Prospects for new therapies and research

Stoffel thinks that through their work they were able to determine the elements that are most important for the uptake mechanism. However, he says it is very likely that yet more molecules play a part. But since an insight into the mechanism now exists for the first time, it will be possible to make specific improvements in the technique. For example Stoffels group wants to find out whether HDL and LDL can be replaced by synthetic proteins or lipid-rich particles. He says that basically the technique has the potential to be used in gene therapy. However, the determination of the siRNA doors also opens up new approaches to fundamental research. Instead of siRNA it might also be possible to smuggle in miRNAs, another group of small RNAs, in the same way. The same mechanism ought to work for miRNA inhibitors as well. Since miRNA is increasingly suspected of occupying a decisive role in gene regulation in nature, its targeted administration or inhibition could yield completely new insights.


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Contact: Professor Marcus Stoffel
41-446-334-560
Swiss Federal Institute of Technology
Source:Eurekalert

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