April 28, 2010
Contact: Public Affairs and Publications


Research by UMMS RNA leaders provides powerful gene-silencing technique

WORCESTER, Mass.—The University of Massachusetts Medical School (UMMS) has been granted United States Patent 7,691,995, entitled, “In Vivo Production of Small Interfering RNAs That Mediate Gene Silencing.” The patent, issued on April 6, 2010, is based on research performed at UMMS by co-inventors Phillip D. Zamore, PhD, Howard Hughes Medical Institute Investigator and the Gretchen Stone Cook Chair of Biomedical Sciences; Craig C. Mello, PhD, Howard Hughes Medical Institute Investigator, the Blais University Chair in Molecular Medicine and 2006 Nobel Laureate; Juanita McLachlan and Gyorgy Hutvagner, members of the Zamore laboratory; and Alla Grishok from the Mello laboratory.

The patent claims cover a powerful technique drawing on a fundamental mechanism in basic biology: using naturally occurring, endogenous microRNA (miRNA) precursors as templates for designing siRNAs to selectively modulate expression of a target gene. This method has found broad application as a tool for gene discovery and analysis in basic research and drug discovery, where such constructs are often called shRNAs or miRNA-based shRNAs.

MicroRNAs occur naturally in cells, whereas engineered siRNAs are designed and introduced into the cell via an external method. In the technology covered by this patent, modifications are made to engineer an siRNA molecule for a specific target gene. Because these engineered siRNAs are based on naturally-occurring miRNA sequences, they can be processed via the cell’s normal gene-silencing machinery, thereby imitating gene regulation at an endogenous level. The patent also covers the inclusion of selected regulatory sequences in the engineered siRNA that allows for controlled expression of the siRNA at specific times or locations in the cell, providing the ability to study the effects of gene silencing in a temporal fashion in vivo.

“We are excited that the U.S. Patent and Trademark Office has recognized our pioneering invention for expressing siRNAs in vivo. MicroRNA-based shRNAs have become a key tool to repress gene expression in cultured cells and whole animals, from flies to mammals, enabling whole genome screens even in living mice,” said Dr. Zamore.

“We are very pleased that the Patent Office has recognized the novel and valuable research conducted by UMass Medical School researchers into the rapidly evolving field of RNA interference,” said James P. McNamara, PhD, executive director of the Office of Technology Management at UMMS. “We believe that the claims covered by this allowed patent application have the potential to play an important role in the tremendous promise of RNA interference in the therapeutic space and in furthering our knowledge of the underlying biological processes in cellular function and gene expression.”

“This is a powerful approach for gene silencing. It allows one to design reagents and therapeutics that take advantage of the natural structural features and cellular mechanisms that drive small RNA processing and function in all our cells,” said Dr. Mello.

“This invention has the potential to greatly enhance the safety and effectiveness of RNA-based therapies, by working with natural mechanisms within a patient’s cells,” said Terence R. Flotte, MD, dean of the School of Medicine. “The partnership that allowed for this discovery is emblematic of the collaborative atmosphere at UMMS.”

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 $240 million in research funding annually, 80 percent of which comes from federal funding sources. The mission of the Medical School is to advance the health and well-being of the people of the commonwealth and the world through pioneering education, research, public service and health care delivery with its clinical partner, UMass Memorial Health Care. For more information, visit