Diabetes and Atherosclerosis
Excessive inflammation, normally part of the body's response to injury or infection, is now known to promote such prevalent diseases as rheumatoid arthritis, diabetes and atherosclerosis. In all of these diseases, the associated inflammation is caused in part by the actions of cells of the human immune system called macrophages. These cells normally recognize and defend against foreign invaders such as bacteria. However, in these diseases they inappropriately damage normal body cells and tissues. Some medicines have been developed to block this damage, but they also blocking desirable immune responses to infection and cancer. The challenge for future research is to find ways to selectively inhibit the disease-causing actions of macrophages that damage tissues, but still allow them to kill bacteria and cancer cells.
To meet this challenge, we are trying to turn off or "silence" the macrophage genes required for tissue-damaging inflammation. To accomplish this, we are using a new technology discovered at UMass Medical School, RNA interference or "RNAi." RNAi can be designed to silence specific genes, making it a promising therapy to treat human disease. However, one obstacle blocks our using RNAi technology to make new medicines for human diseases: getting the RNA molecules that trigger RNAi safely and effectively to the specific tissues or cells in the body where they are needed. If we can design methods to over come this obstacle—which we call the "delivery problem"—we believe we will be able to treat many diseases related to inflammation.
We collaborate with Dr. Gary Ostroff's research group to develop new ways to deliver RNA molecules to macrophages in those cells and organs that are damaged in inflammatory diseases. We are now testing a unique "encapsulation technology" as a potential way to get RNA to the right places in the body. Our strategy uses particles derived from ordinary baker's yeast to make a hollow ball with the RNA inside. The yeast shell protects the RNA as it travels through the body and encourages macrophages to "eat" the particles, getting the RNA inside the right cells. The strategy takes advantage of the special ability of macrophages to engulf and absorb small particles, delivering the contents of the particles into the cells. This allows the contents of the particles to have a therapeutic effect. We have shown that this strategy can work in mice to treat inflammation. We are continuing to improve the particles and to test them in mice that mimic the human diseases atherosclerosis and diabetes.
Dr. Michael Czech
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