UMMS RESEARCHERS RECEIVE $6 MILLION TRANSFORMATIVE AWARD FROM THE NATIONAL INSTITUTES OF HEALTH TO PURSUE ORAL DELIVERY OF RNAi THERAPEUTICS

Investigators to test efficiency, extent and duration of gene silencing using siRNA in inflammation models involved in type-2 diabetes

September 24, 2009

WORCESTER, Mass. – 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.

The NIH has granted a total of $30 million to 42 Director’s Transformative R01 (t-R01) Awards in fiscal year 2009, the first year of the program’s existence. Named for the standard investigator-initiated research project that the NIH supports, the R01, the T-R01s provide a new opportunity for scientists that is unmatched by any other NIH program. Since no budget cap is imposed and preliminary results are not required, scientists are free to propose new, bold ideas that may require significant resources to pursue. They are also given the flexibility to work in large, complex teams if the complexity of the research problem demands it.

More information on the Transformative R01 Award is at http://nihroadmap.nih.gov/T-R01.

For descriptions of the 2009 recipients’ research plans, see http://nihroadmap.nih.gov/T-R01/Recipients09.asp.

About the University of Massachusetts Medical School
The University of Massachusetts Medical School, one of the fastest growing academic health centers in the country, has built a reputation as a world-class research institution, consistently producing noteworthy advances in clinical and basic research. The Medical School attracts more than $200 million in research funding annually, 80 percent of which comes from federal funding sources. The work of UMMS researcher Craig Mello, PhD, an investigator of the prestigious Howard Hughes Medical Institute (HHMI), and his colleague Andrew Fire, PhD, then of the Carnegie Institution of Washington, toward the discovery of RNA interference was awarded the 2006 Nobel Prize in Medicine and has spawned a new and promising field of research, the global impact of which may prove astounding. UMMS is the academic partner of UMass Memorial Health Care, the largest health care provider in Central Massachusetts. For more information, visit www.umassmed.edu.



About the NIH Common Fund and the Director’s Transformative R01 Program
The NIH Common Fund encourages collaboration and supports a series of exceptionally high impact, trans-NIH programs known collectively as the NIH Roadmap for Medical Research. The NIH Director’s Transformative R01 program is part of the NIH Roadmap. It is funded through the Common Fund and managed by the NIH Office of the Director and the National Institute of General Medical Sciences, respectively. The Roadmap is a series of initiatives designed to pursue major opportunities and gaps in biomedical research that no single NIH institute could tackle alone, but that the agency as a whole can address to make the biggest impact possible on the progress of medical research. Additional information about the NIH Roadmap can be found at www.nihroadmap.nih.gov.

The Office of the Director, the central office at NIH, is responsible for setting policy for NIH, which includes 27 Institutes and Centers. This involves planning, managing, and coordinating the programs and activities of all NIH components. The Office of the Director also includes program offices which are responsible for stimulating specific areas of research throughout NIH. Additional information is available at http://www.nih.gov/icd/od/.

The National Institutes of Health (NIH) — The Nation's Medical Research Agency — includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. It is the primary federal agency for conducting and supporting basic, clinical and translational medical research, and it investigates the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.