UMMS RESEARCHERS MAKE BREAKTHROUGH IN DELIVERY OF RNA INTERFERENCE 
Investigators design new nanomaterials for the safe, efficient delivery of RNAi 

April 13, 2007 

WORCESTER, Mass.-With the recent awarding of the 2006 Nobel Prize in Physiology or Medicine to its co-discoverers, RNA interference (RNAi) has been further validated as an exceptionally promising tool in the effort to better human health. An evolutionarily conserved phenomenon, RNAi has been proven as a fast and efficient method to silence individual gene expression. Now widely used in labs across the world to assess gene function, RNAi is also being examined as a potential therapy for a range of genetic disorders and diseases. 

However, the development of RNAi therapeutics has been faced with a number of challenges, including the identification of chemically stable and effective silencing sequences and the creation of a mechanism by which RNAi could safely be delivered to humans. Now, researchers from the University of Massachusetts Medical School (UMMS) report on a breakthrough-the development of new systemic agents that are able to silence disease-related genes in clinically acceptable and therapeutically affordable doses that require a small amount of RNA drugs without causing undesirable toxic and immunogenic effects. 

In "Design and Creation of New Nanomaterials for Therapeutic RNAi," published today in an advanced online issue  of ACS Chemical Biology, UMMS Professor of Biochemistry and Molecular Pharmacology Tariq M. Rana, PhD, and colleagues report on the design and creation of interfering nanoparticles, or iNOPs. Comprised of two subunits - a nanoparticle-based delivery agent and a chemically modified short interfering RNA (siRNA), which can program RNAi in cells - the iNOPs were able to silence an endogenous gene found in the liver, resulting in the lowering of the total plasma cholesterol in the tested animal models. Further, iNOP treatment was non-toxic and did not induce an immune response.  

The investigators caution that additional studies are needed to fully determine the safety of the nanoparticles. "One concern about applying nanotechnology in biology and medicine is its safety. Nanomaterials used to deliver a drug could cause undesired effects by inhibiting the drug's biodegradation and clearance, thus prolonging its half-life in vivo. Further investigations in this area are essential as we move forward," Dr. Rana explained. 

"Still, our exciting results demonstrate that these newly designed nanoparticles can be used to deliver siRNA to silence disease-related endogenous genes," Rana said. "The low dose of siRNA required in our studies to achieve therapeutic effects provides great hope for developing RNAi-based therapies in the near future to cure diseases caused by proteins that cannot be targeted by conventional drugs." 

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 $176 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 Physiology or Medicine, hailed as the "Breakthrough of the Year" in 2002 by Science magazine 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 . 

Contact: Kelly Bishop, 508-856-2000