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

More articles from Life Sciences:

nachricht Cancer diagnosis: no more needles?
25.05.2018 | Christian-Albrechts-Universität zu Kiel

nachricht Less is more? Gene switch for healthy aging found
25.05.2018 | Leibniz-Institut für Alternsforschung - Fritz-Lipmann-Institut e.V. (FLI)

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Powerful IT security for the car of the future – research alliance develops new approaches

The more electronics steer, accelerate and brake cars, the more important it is to protect them against cyber-attacks. That is why 15 partners from industry and academia will work together over the next three years on new approaches to IT security in self-driving cars. The joint project goes by the name Security For Connected, Autonomous Cars (SecForCARs) and has funding of €7.2 million from the German Federal Ministry of Education and Research. Infineon is leading the project.

Vehicles already offer diverse communication interfaces and more and more automated functions, such as distance and lane-keeping assist systems. At the same...

Im Focus: Molecular switch will facilitate the development of pioneering electro-optical devices

A research team led by physicists at the Technical University of Munich (TUM) has developed molecular nanoswitches that can be toggled between two structurally different states using an applied voltage. They can serve as the basis for a pioneering class of devices that could replace silicon-based components with organic molecules.

The development of new electronic technologies drives the incessant reduction of functional component sizes. In the context of an international collaborative...

Im Focus: LZH showcases laser material processing of tomorrow at the LASYS 2018

At the LASYS 2018, from June 5th to 7th, the Laser Zentrum Hannover e.V. (LZH) will be showcasing processes for the laser material processing of tomorrow in hall 4 at stand 4E75. With blown bomb shells the LZH will present first results of a research project on civil security.

At this year's LASYS, the LZH will exhibit light-based processes such as cutting, welding, ablation and structuring as well as additive manufacturing for...

Im Focus: Self-illuminating pixels for a new display generation

There are videos on the internet that can make one marvel at technology. For example, a smartphone is casually bent around the arm or a thin-film display is rolled in all directions and with almost every diameter. From the user's point of view, this looks fantastic. From a professional point of view, however, the question arises: Is that already possible?

At Display Week 2018, scientists from the Fraunhofer Institute for Applied Polymer Research IAP will be demonstrating today’s technological possibilities and...

Im Focus: Explanation for puzzling quantum oscillations has been found

So-called quantum many-body scars allow quantum systems to stay out of equilibrium much longer, explaining experiment | Study published in Nature Physics

Recently, researchers from Harvard and MIT succeeded in trapping a record 53 atoms and individually controlling their quantum state, realizing what is called a...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

In focus: Climate adapted plants

25.05.2018 | Event News

Save the date: Forum European Neuroscience – 07-11 July 2018 in Berlin, Germany

02.05.2018 | Event News

Invitation to the upcoming "Current Topics in Bioinformatics: Big Data in Genomics and Medicine"

13.04.2018 | Event News

 
Latest News

In focus: Climate adapted plants

25.05.2018 | Event News

Flow probes from the 3D printer

25.05.2018 | Machine Engineering

Less is more? Gene switch for healthy aging found

25.05.2018 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>