RNA interference (RNAi) represents a revolutionary approach to basic biological research as well as drug development and discovery. The ability to genetically manipulate mammalian cells with RNAi may lead to critical insights into the mechanisms underlying human disease and accelerate the development of treatments for cancer, AIDS, and a host of other disorders.
A public-private consortium based at the Broad Institute is developing RNAi technologies that will enable the scientific community to probe the functions of human and mouse genes. The goal of the RNAi Consortium (abbreviated TRC) is to create widely applicable research reagents consisting of specific RNAi inhibitors targeting human and mouse genes. The reagents are composed of short hairpin sequences carried in lentiviral vectors. They can be used in a wide range of cellular and animal studies to discover the key genes underlying normal physiology and disease.
The first phase of TRC's efforts is now complete. The researchers involved in the three-year, $18 million initiative successfully built a library of 160,000 custom-designed RNAi constructs targeting 15,000 human genes and 15,000 mouse genes. They also developed methods to apply this library effectively for loss-of-function genetic screens. This fundamental resource is available to scientists worldwide through Sigma-Aldrich and GE Healthcare Dharmacon.
The project's second phase, a four-year collaboration launched in 2007 and known as TRC2, will further enhance this RNAi resource. A key goal is to provide at least two RNAi reagents for each human and mouse gene that achieve a high knockdown efficiency. Work toward this goal will include functional validation as well as efforts to improve library design. The consortium also hopes to enable widespread applications of RNAi by further developing and improving RNAi screening strategies.
In addition to the Broad Institute, TRC2 partners include Harvard Medical School (HMS), the Massachusetts Institute of Technology (MIT), Dana-Farber Cancer Institute (DFCI), Massachusetts General Hospital (MGH), the Whitehead Institute for Biomedical Research (WIBR), Bristol-Myers Squibb, Johnson & Johnson, the Ontario Institute of Cancer Research, Sigma-Aldrich, and research institute Academia Sinica in Taiwan.
The principal investigators of TRC2 are Dr. Nir Hacohen (Broad Institute associate member; MGH, HMS), Dr. William Hahn (Broad Institute associate member; DFCI, HMS), Dr. Eric Lander (Broad Institute), Dr. David Root (TRC Project Leader, Broad Institute), and Dr. David Sabatini (Broad Institute associate member; WIBR, MIT).
TRC phase 1 participants also included principal investigators Dr. Sheila Stewart (Washington University, formerly at WIBR), and Dr. Brent Stockwell (Columbia University, formerly at WIBR). Past sponsors include Novartis and Eli Lilly.
The TRC shRNA library is distributed as bacterial glycerol stocks, plasmid DNA or lentiviral particles by Sigma-Aldrich and as bacterial glycerol stocks by GE Healthcare Dharmacon. The Broad Genetic Perturbation Platform does not directly distribute the TRC library.