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MGH, Alnylam, MIT Researchers Report on siRNA Inhibition of Inflammation

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Massachusetts General Hospital last week published data showing that siRNAs could be used to block inflammation in mice by silencing CCR2 in monocytes.

Investigators from Alnylam Pharmaceuticals and the Massachusetts Institute of Technology contributed to the report, which appeared in Nature Biotechnology.

“Inflammatory monocytes, but not the non-inflammatory subset, depend on the chemokine receptor CCR2 for localization to injured tissue,” the researchers wrote.

Using an optimized lipid nanoparticle, siRNAs against CCR2 were delivered systemically into the mice. The compound showed rapid blood clearance, and accumulated in spleen and bone marrow while localizing to monocytes.

As a result, the monocytes did not accumulate in sites of inflammation, according to the paper.

“Specifically, the treatment attenuates their number in atherosclerotic plaques, reduces infarct size after coronary artery occlusion, prolongs normoglycemia in diabetic mice after pancreatic islet transplantation, and results in reduced tumor volumes and lower numbers of tumor-associated macrophages,” the authors wrote.

"Anti-inflammatory drugs currently on the market hit every inflammatory cell in the body, which can produce unwanted side effects,” Matthias Nahrendorf, member of MGH's Center for Systems Biology and the paper's senior author, said in a statement. “This new siRNA treatment doesn't affect inflammatory cells that don't rely on the CCR2 receptor. That makes a big difference.”

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