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Consortium to create comprehensive tools for uncovering the functions of human, mouse genes


Eleven leading biomedical organizations announced today the formation of a unique $18M, three-year public-private consortium to create a comprehensive library of gene inhibitors to be made available to the entire scientific community. Based on the method of RNA interference (RNAi), this library will give scientists worldwide the tools to knock down expression of virtually all human and mouse genes, accelerating the growth of basic knowledge of gene function in normal physiology and disease.

Called The RNAi Consortium (TRC), the collaborative effort is based at the Broad Institute of MIT and Harvard, and includes six MIT- and Harvard-associated research institutions and five international life sciences organizations.

The goal of TRC is to use the recently discovered RNAi mechanism to create widely applicable research reagents composed of short RNA hairpin sequences carried in lentiviral vectors. These can be used in a wide range of cellular and animal studies to discover the key genes underlying normal physiology and diseases – including cancer, diabetes and immunological responses. TRC will not only create and validate these reagents, but will make them available to scientists worldwide through commercial and academic distributors.

TRC is based on a scientific collaboration among principal investigators at six Boston-area research institutions: Nir Hacohen (Massachusetts General Hospital, Harvard Medical School); William Hahn (Dana-Farber Cancer Institute, Harvard Medical School); Eric Lander (Broad Institute); David Root (Broad Institute); David Sabatini (Whitehead Institute for Biomedical Research [WIBR], Massachusetts Institute of Technology; Sheila Stewart (Washington University, formerly at WIBR), and Brent Stockwell (Columbia University, formerly at WIBR).

TRC also involves five member organizations: Pharmaceutical companies Bristol-Myers Squibb, Eli Lilly and Company, and Novartis; research product manufacturer Sigma-Aldrich; and a Taiwan government-sponsored academic consortium, Academia Sinica-National Science Council. Each of the member organizations will contribute $3.6M over three years to support the effort.

"These 11 world-class entities will make common cause in a unique collaborative group to create a public good: a comprehensive set of reagents to be used in thousands of laboratories," said Lander, director of the Broad Institute and one of TRC principal investigators. "In addition, the organizations will each benefit from sharing their expertise to advance the technology and to accelerate its systematic application in basic biomedical research and drug discovery."

The members and principal investigators will work together over the three-year period to share expertise about ways to use RNAi technology to speed biomedical research. The project also will develop efficient protocols for preparing DNA and virus stocks of the RNAi reagents and will create methods for performing high-throughput screening with the entire library.

"We are pleased to be a part of the RNAi Consortium, as it promises to be a highly important resource for the scientific research community," said Elliott Sigal, chief scientific officer and president of the Pharmaceutical Research Institute of Bristol-Myers Squibb. "We believe that the outputs of the consortium will contribute greatly to the understanding of gene function and to the development of new medicines."

"The ability to perform high-throughput screening with validated RNAi reagents will provide the ability to systematically identify the genes underlying disease process and thereby identify previously unknown targets for drug discovery," said Steven Paul, executive vice president of Lilly Research Laboratories, Eli Lilly and Company. "We’re proud to contribute to this important public cause, while being leading users of the technology ourselves."

"In order to advance pharmaceutical science, fundamental tools like RNAi need to be made available and accessible to scientists around the world. We’re delighted to help make that possible," said Mark Fishman, president of Novartis Institutes for BioMedical Research. "The RNAi Consortium is an excellent example of how industry and academia can work together."

"Sigma Aldrich is looking forward to participating in the development of these reagents and the associated methods," said Dave Julien, president of biotechnology at Sigma-Aldrich. "The TRC is consistent with our goal of enabling progress in biomedical research."

Separately, Sigma said that it plans to commercially distribute clones, purified DNA and viral stocks from TRC RNAi libraries, facilitating their use by researchers worldwide. In addition, TRC will make the clones available to other commercial and academic groups.

"We are excited by the enormous prospects of using systematic RNAi screening to help understand cell biology and disease," said Professor Michael Lai, vice president of Academia Sinica. "We are glad that the scientific community of Taiwan can participate in this unique international effort."

RNAi technology

RNAi is expected to revolutionize drug development and discovery by providing critical insights into the mechanism underlying human disease and accelerating development of medical treatments for cancer, metabolic, inflammatory, infectious, neurological and other types of diseases.

RNAi provides a means of dissecting complex biological processes by switching off genes one at a time. This approach could reveal the genes that are key to a variety of diseases, including those genes critical to a cancer cell’s survival, genes that promote resistance to HIV or genes that mediate diabetes.

Over three years, TRC will create the materials needed to conduct RNAi experiments on 15,000 human genes and 15,000 mouse genes. A total of 150,000 custom-designed plasmids that express short, unique pieces of RNA (known as short hairpin RNAs or shRNAs) that target specific genes will enable the systematic investigation of most human and mouse genes. A powerful feature of this library is that it can be efficiently transformed into a viral mode that is easily introduced into many cell lines and primary cells used in biomedical research.

Although researchers worldwide are investigating RNAi as a promising novel approach to gene therapy, TRC’s primary focus is on developing RNAi as a biomedical research tool.

Michelle Nhuch | EurekAlert!
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