RNA interference gives researchers around the globe precise tool to fight disease

February 11, 2003

WORCESTER, Mass.—Harnessing a vital cellular process, researchers at the University of Massachusetts Medical School and the Carnegie Institution of Washington have developed a method by which ribonucleic acid (RNA), the cellular material responsible for the transmission of genetic information, can silence a targeted gene within a living cell. The process, called RNA interference (RNAi), can shut down disease-causing genes—or direct researchers to pathways for effective drug development—and thus opens up an astounding new avenue for understanding gene function. UMMS and Carnegie have recently secured a patent for the application of the process, which is expected to have broad implications for disease treatment and drug development.

Cells with a target gene may be derived from or contained in any living organism: plant, animal, bacterium, virus or fungus. For example, a particular gene in a plant might be silenced to reduce susceptibility to bacteria or fungi. 

Craig C. Mello, PhD, a Howard Hughes Medical Institute Investigator and associate professor of molecular medicine and cell biology at UMMS, and Carnegie’s Andrew Fire, PhD, and their colleagues discovered, to the surprise of the research community, that double-stranded RNA had the unanticipated property of silencing the expression of a gene whose coding sequence of DNA was similar to that of the RNA they tested.  The single-stranded RNA molecule is commonly known for its role in shuttling the genetic code contained in DNA from the cell’s nucleus to its ribosomes where proteins are made, and for making sure that the proteins are correctly constructed to perform their functions in living organisms. In RNAi, the first strand of double-stranded RNA molecule has the ribonucleotide sequence that matches the nucleotide sequence in the targeted gene; the second strand of RNA has a complementary sequence to that in the target gene. When introduced to an organism, the double stranded RNA degrades a specific messenger RNA (mRNA) molecule, which disrupts the message-carrying process and inactivates the gene, essentially halting the progression of an invading viral infection or, for example, tumor growth.

RNAi is now the state-of-the-art method by which scientists can knock down the expression of specific genes in cells, to thus define the biological functions of those genes.

“It has been extremely exciting and rewarding to see RNA interference grow as a research tool and field of study—from a strange phenomenon in a simple microscopic worm into so many exciting new discoveries and whole new research fields,” said Mello.

Fire agreed, adding, “Given the fundamental and broad-based impact of RNAi, I am extremely pleased that we can make this widely available to researchers at universities and other institutions seeking answers to genetic puzzles. I look forward to what I think will be astonishing discoveries that will result from the use of RNAi.”

The patent, “Genetic Inhibition by Double-Stranded RNA,” (US Patent 6,506,559 B1) issued to UMMS and Carnegie, is expected to have far-reaching licensing potential both in the lab and in drug development. Because both institutions were eager to bring RNAi to bear as broadly as possible to hasten genetic research, they developed a licensing policy by which companies can readily obtain, for a basic fee, a wide-ranging and non-exclusive license to use the technology. A significant number of companies have already licensed the invention and additional companies have expressed interest. 

Mello and Fire’s work in RNA and RNA interference was recently hailed as an “electrifying discovery” and the “Breakthrough of the Year” by Science magazine and has had an extraordinary impact on biological science. The two researchers were also recently awarded the prestigious Award in Molecular Biology from the National Academy of Sciences, a private, non-profit, self-perpetuating society of distinguished scholars engaged in scientific and engineering research, dedicated to the furtherance of science and technology and to their use for the general welfare. The NAS, which also advises the federal government on scientific and technical matters, selects just 18 individual researchers to receive awards honoring their outstanding scientific achievements. This year’s awards will be presented April 28 at a ceremony during the NAS 140th annual meeting, in Washington DC. (See for the full article from the December 2002 issue of Science. Additional information about the National Academy of Science is available at .)

Mello, who holds degrees from Brown University (BS in Biochemistry) and Harvard University (PhD in Cellular and Developmental Biology), was a postdoctoral fellow at the Fred Hutchinson Cancer Research Center in Seattle before coming to UMMS in 1990.  In 2000 he was named an Investigator of the Howard Hughes Medical Institute (HHMI), one of the most prestigious and sought-after scientific awards in the world. HHMI is a $13 billion medical research organization that employs more than 350 eminent researchers at 72 medical schools, universities and research institutes worldwide. Mello, whose research into the genetics of the worm C. elegans provides important insights into human development and cancer, is the third HHMI researcher at UMMS, joining Michael R. Green, MD, PhD, the Lambi and Sarah Adams Chair in Genetic Research and professor of molecular medicine, biochemistry & molecular pharmacology and surgery and director of the Program in Gene Function & Expression; and Roger J. Davis, PhD, the H. Arthur Smith Chair in Cancer Research and professor of molecular medicine and biochemistry & molecular pharmacology.

In addition to Mello’s work in establishing RNAi as a field of study, several other scientists at UMMS are also working in RNAi, particularly Phillip D. Zamore, PhD, associate professor of biochemistry & molecular pharmacology, whose research is focused on identifying the biochemical machinery that brings about RNAi. Specifically, his team is using extracts from fly embryos and human cells, purified in the test tube, in hopes of understanding the phenomenon’s components at the molecular level― research that may eventually form the basis for a new class of drugs to treat human disease, including viral infections and some genetic disorders. Mario Stevenson, PhD, the David J. Freelander Professor of AIDS Research and professor of molecular medicine and molecular genetics & microbiology, is examining the use of one form of RNAi, small interfering or siRNA, to block HIV infection, while Tariq M. Rana, PhD, professor of biochemistry & molecular pharmacology, is studying RNAi in mammalian cells.

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 $143 million in research funding annually, 80 percent of which comes from federal funding sources.  Research funding enables UMMS scientists to explore human disease from the molecular level to large-scale clinical trials.  Basic and clinical research leads to new approaches for diagnosis, treatment and prevention of disease. Visit for additional information.

Alison Duffy, Mark L. Shelton, (508) 856-2000

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