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

CAMBRIDGE, MA -- Researchers from MIT, Alnylam Pharmaceuticals and other institutions have demonstrated the safety of a promising type of genetic therapy that could lead to treatments for a wide range of diseases such as cancer.

The work, which will be published in the Sept. 27 issue of Nature, describes a new approach to conducting the therapy. A paper in Nature last year reported that another commonly used approach caused fatalities in mice.

The research focuses on RNA interference, or RNAi, a key part of the body's genetic machinery. RNAi works by using short strands of RNA to block the expression of specific genes.

RNAi has huge potential as a therapeutic agent, said Daniel Anderson, a research associate at MIT's Center for Cancer Research and one of the authors of the new paper.

However, a paper published in Nature last year by a different team showed that large doses of one type of RNA used for RNAi, short hairpin RNA, disrupted another key RNA pathway, the microRNA pathway, and caused the mice in the study to die. That result worried some RNAi researchers, said Anderson.

That first paper demonstrated that short hairpin RNA could lead to mouse fatality, he said. Researchers were concerned that a second type of RNA, small interfering RNA (siRNA), would induce the same toxicity.

In the current study, the researchers demonstrated that siRNA did not have the same toxic effects as large doses of shRNA because it does not interfere with the microRNA pathway. Further, they achieved 80 percent silencing of target genes in mice and hamster liver cells.

Using chemically synthesized siRNA, you can deliver sufficient siRNA to achieve therapeutically valuable gene silencing, without interfering with the cell's endogenous microRNA, said David Bumcrot, a director of research at Alnylam (an MIT startup) and one of the authors of the paper.

The research team used a new RNA delivery system developed
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Contact: Elizabeth Thomson
thomson@mit.edu
617-258-5402
Massachusetts Institute of Technology
Source:Eurekalert

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