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UMMS Researchers Receive $6 Million Transformative Award from the National Institutes of Health to Pursue Oral Delivery of RNAi Therapeutics
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UMMS Researchers Receive $6 Million Transformative Award from the National Institutes of Health to Pursue Oral Delivery of RNAi Therapeutics

UMMS Researchers Receive $6 Million Transformative Award from the National Institutes of Health to Pursue Oral Delivery of RNAi Therapeutics
News

UMMS Researchers Receive $6 Million Transformative Award from the National Institutes of Health to Pursue Oral Delivery of RNAi Therapeutics

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As part of an effort to support investigators exploring bold ideas that have the potential to catapult fields forward and speed the translation of research into improved health, the National Institutes of Health has awarded researchers at the University of Massachusetts Medical School (UMMS) a 5-year, $6 million Director’s Transformative R01 (t-R01) Award to continue pursuit of a novel approach to the delivery of small pieces of genetic material in order to silence genes using “RNA interference. Investigators at UMMS will attempt to quantify and control the delivery, distribution and efficacy of short pieces of RNA to suppress the genes in immune cells responsible for insulin resistance and inflammation associated with type 2 diabetes.

“RNAi-based therapies have the potential to transform the practice of medicine for numerous major human diseases such as diabetes, rheumatoid arthritis and atherosclerosis,” said Michael P. Czech, PhD, principle investigator of the study, who is chair and professor of molecular medicine and biochemistry & molecular pharmacology at UMMS. “This grant will allow us to potentially answer major questions about the delivery of short strands of double stranded RNA to specific target tissue that could have far-ranging implications for potential future therapies.”

The discovery in 1998 that short strands of RNA can silence the action of a given gene changed the scientific world’s understanding of how genes are regulated. Highly specific and highly potent, “RNA interference” or “RNAi” has become both a crucial laboratory technique and widely studied for potential therapeutic applications; the explanation of the mechanism of RNAi was recognized with the 2006 Nobel Prize in Medicine, awarded to UMMS Professor Craig C. Mello, PhD, and collaborator Andrew Z. Fire, PhD, of Stanford University. Since the discovery, laboratories around the world have focused on the potential of RNAi to silence genes with high specificity, low toxicity and minimal immune system response.

But how to deliver tiny strands of genetic material into cells in a living organism has been a formidable obstacle. In previous studies, Czech and his collaborator Gary R. Ostroff, PhD, and their colleagues at UMMS have successfully engineered small encapsulating particles containing short pieces of RNA, which dramatically silenced genes in mice following oral administration in small doses. Research supported by the Transformative Award will target delivery of small RNA particles to a type of white blood cell called a macrophage. These cells engulf and digest cellular debris and respond to invading organisms by stimulating the immune response. Because macrophages control the inflammatory response in diseases such as diabetes and atherosclerosis (a precursor to heart disease), they represent an attractive target for drug delivery. An initial proof-of-effectiveness study will focus on controlling macrophage inflammation in models of type-2 diabetes.
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