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Team demos safety of RNA therapy
Date:9/26/2007

at MIT, the details of which will be published in another upcoming paper, to perform the RNA interference.

In many RNAi studies, including the one that the MIT/Alnylam team was following up on, researchers use retroviruses to deliver genes that code for short hairpin RNA, which is a precursor to siRNA. Once the gene is incorporated into the cell's DNA, short hairpin RNA is synthesized and transported from the cell nucleus to the cytoplasm for further processing.

The earlier study showed that large amounts of short hairpin RNA blocked the cell's ability to export microRNA, which uses the same export pathway. Without normally functioning microRNA, the mice died. Low doses of short hairpin RNA were not toxic, but the dosage is difficult to control because once the shRNA gene is incorporated into the DNA of the host cells, it is expressed for long periods of time, said Bumcrot.

In the current MIT/Alnylam study, siRNA was delivered directly to the cell cytoplasm, so it did not compete with the export of microRNA.

We wanted to demonstrate that if you go downstream of that (export) step in the pathway, you don't get interference with the microRNA pathway, said Bumcrot. With synthetic siRNAs, we deliver a defined dose and we know how long the effect lasts. If toxicity issues arise, dosing can be stopped at any time. It's much easier to control and, therefore, safer.


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Contact: Elizabeth Thomson
thomson@mit.edu
617-258-5402
Massachusetts Institute of Technology
Source:Eurekalert

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