Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Novel technique uses RNA interference to block inflammation

11.10.2011
Interfering with cell recruitment reduces damaging inflammation in animals models of several disorders

Massachusetts General Hospital (MGH) researchers – along with collaborators from Massachusetts Institute of Technology (MIT) and Alnylam Pharmaceuticals – have found a way to block, in an animal model, the damaging inflammation that contributes to many disease conditions.

In their report receiving early online publication in Nature Biotechnology, the investigators describe using 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," says Matthias Nahrendorf, MD, PhD, of the MGH Center for Systems Biology, the paper'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."

Cells damaged by injury or disease release a cocktail of chemicals called cytokines that attract immune cells to the site of the damage. 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 associated messenger RNA molecules and preventing their translation. Because the technique requires extreme precision in developing the right siRNA molecule and delivering it to the correct cellular location, the MGH team collaborated with Alnylam scientists who are experts in RNA-interference-based therapeutics and with MIT investigators Robert Langer, ScD, and Daniel Anderson, PhD, who have developed a nanoparticle-based system for delivering molecules to specific cellular compartments.

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 showed 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 showed 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.

"These inflammatory monocytes are involved in almost every major disease," Nahrendorf explains. "Anti-inflammatory drugs currently on the market hit every inflammatory cell in the body, which can produce unwanted side effects. This new siRNA treatment doesn't affect inflammatory cells that don't rely on the CCCR2 receptor. That makes a big difference." Nahrendorf is an assistant professor of Radiology at Harvard Medical School.

Florian Leuschner and Partha Dutta of the MGH Center for Systems Biology are co-lead authors of the paper. Additional co-authors are Rostic Gorbatov, Jessica Donahoe, Gabriel Courties, Brett Marinelli, Yoshiko Iwamoto, Virna Cortez-Retamozo, Andita Newton, Mikael Pittet, Filip Swirski and Ralph Weissleder, MGH Center for Systems Biology; Tatiana Novobrantseva, Stuart Milstein, Hila Epstein-Barash, William Cantley, Jamie Wong, and Victor Koteliansky, Alnylam Pharmaceuticals; Kang Mi Lee, James Kim and James Markmann, MGH Department of Surgery; Peter Panizzi, Auburn University; Won Woo Lee, Seoul National University; Kevin Love, Massachusetts Institute of Technology; and Peter Libby, Brigham and Women's Hospital. The study was supported by grants from the National Institute of Health and other funders.

Celebrating the 200th anniversary of its founding in 1811, Massachusetts General Hospital (www.massgeneral.org) is the original and largest teaching hospital of Harvard Medical School. MGH conducts the largest hospital-based research program in the United States, with an annual research budget of nearly $700 million and major research centers in AIDS, cardiovascular research, cancer, computational and integrative biology, cutaneous biology, human genetics, medical imaging, neurodegenerative disorders, regenerative medicine, reproductive biology, systems biology, transplantation biology and photomedicine.

Sue McGreevey | EurekAlert!
Further information:
http://www.massgeneral.org

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: A Chip with Blood Vessels

Biochips have been developed at TU Wien (Vienna), on which tissue can be produced and examined. This allows supplying the tissue with different substances in a very controlled way.

Cultivating human cells in the Petri dish is not a big challenge today. Producing artificial tissue, however, permeated by fine blood vessels, is a much more...

Im Focus: A Leap Into Quantum Technology

Faster and secure data communication: This is the goal of a new joint project involving physicists from the University of Würzburg. The German Federal Ministry of Education and Research funds the project with 14.8 million euro.

In our digital world data security and secure communication are becoming more and more important. Quantum communication is a promising approach to achieve...

Im Focus: Research icebreaker Polarstern begins the Antarctic season

What does it look like below the ice shelf of the calved massive iceberg A68?

On Saturday, 10 November 2018, the research icebreaker Polarstern will leave its homeport of Bremerhaven, bound for Cape Town, South Africa.

Im Focus: Penn engineers develop ultrathin, ultralight 'nanocardboard'

When choosing materials to make something, trade-offs need to be made between a host of properties, such as thickness, stiffness and weight. Depending on the application in question, finding just the right balance is the difference between success and failure

Now, a team of Penn Engineers has demonstrated a new material they call "nanocardboard," an ultrathin equivalent of corrugated paper cardboard. A square...

Im Focus: Coping with errors in the quantum age

Physicists at ETH Zurich demonstrate how errors that occur during the manipulation of quantum system can be monitored and corrected on the fly

The field of quantum computation has seen tremendous progress in recent years. Bit by bit, quantum devices start to challenge conventional computers, at least...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

“3rd Conference on Laser Polishing – LaP 2018” Attracts International Experts and Users

09.11.2018 | Event News

On the brain’s ability to find the right direction

06.11.2018 | Event News

European Space Talks: Weltraumschrott – eine Gefahr für die Gesellschaft?

23.10.2018 | Event News

 
Latest News

Epoxy compound gets a graphene bump

14.11.2018 | Materials Sciences

Microgel powder fights infection and helps wounds heal

14.11.2018 | Health and Medicine

How algae and carbon fibers could sustainably reduce the athmospheric carbon dioxide concentration

14.11.2018 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>