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ALNYLAM RELEASES DATA ON GENE SILENCING FOR ACUTE LUNG INJURY

November 7, 2006

Alnylam Pharmaceuticals has announced the publication of preclinical data demonstrating that an RNAi therapeutic can silence angiopoietin 2 (Ang2), a key mediator in acute lung injury. In a paper published in Nature Medicine, scientists from Yale University and Alnylam demonstrated inhibition of acute lung injury and cell death in animals with administration of small interfering RNAs (siRNAs), the molecules that mediate RNAi, targeting Ang2. These in vivo data showed silencing of Ang2 in the lung, and contribute to existing data demonstrating the potential for developing RNAi therapeutics that target diseases associated with the lung, such as respiratory syncytial virus infection, influenza and asthma.

RNAi is a naturally occurring mechanism within cells for selectively silencing and regulating specific genes. RNAi is induced by small, double-stranded RNA molecules. One method to activate RNAi is with chemically synthesized small interfering RNAs, or siRNAs, which are double-stranded RNAs that are targeted to a specific disease-associated gene. The siRNA molecules are used by the natural RNAi machinery in cells to cause highly targeted gene silencing.

The study demonstrated that acute lung injury caused by cell death, high and potentially toxic concentrations of oxygen (hyperoxia), and the resulting excess fluid in the lungs (pulmonary edema), may be controlled by the Ang2 protein. Data showed that local intranasal administration in mice of an siRNA targeting Ang2 resulted in specific inhibition of messenger RNA by more than 60 percent. A proportionate drop in Ang2 protein levels was also observed. In addition, acute lung injury was reduced to near noninjury levels as measured by statistically significant reductions in lung inflammation and cell death. Messenger RNA levels of other genes were not affected by administration of the siRNA, including VEGF, Bcl-2 and ß-actin.