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Novel technique uses RNA interference to block harmful inflammations

October 10, 2011 - London

Scientists have found a way to block the damaging inflammation that contributes to many disease conditions in an animal model.

Massachusetts General Hospital (MGH) researchers - along with collaborators from Massachusetts Institute of Technology (MIT) and Alnylam Pharmaceuticals - were behind the findings.

The investigators described how they used small interfering RNA technology to silence the biochemical signals that attract a particular group of inflammatory cells to areas of tissue damage.

"The white blood cells known as monocytes play a critical role in the early stages of the immune response," said Matthias Nahrendorf, MD, PhD, of the MGH Centre for Systems Biology, the study's senior author.

"We now know there are two subsets of monocytes - an inflammatory subset that defends against pathogens and a reparative subset that supports healing. But if the inflammatory response is excessive, it can block the healing process and exacerbate conditions such heart disease and cancer," he stated.

Inflammatory monocytes are guided to sites of tissue injury by a receptor Protein called CCR2, and the MGH-led team devised a strategy targeting that molecule to block the inflammatory process but not the action of the reparative monocytes.

Small interfering RNA (siRNA) technology prevents production of specific Proteins by binding to messenger RNA molecules and preventing their translation.

To make sure that their siRNA preparation targeted the right monocytes, the investigators first confirmed that its use reduced levels of CCR2 in monocytes and increased levels of the fragments produced when siRNA binds to its target.

They then found that monocytes from mice treated with the siRNA preparation were unable to migrate towards CCR2's usual molecular target.

Experiments in animal models of several important diseases also found that the siRNA preparation reduced the amount of cardiac muscle damaged by a Heart attack, reduced the size and the number of inflammatory cells in atherosclerotic plaques and in lymphomas, and improved the survival of transplanted pancreatic islets.

The study was published online in Nature Biotechnology.


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