Sigma-Aldrich Validates shRNA Libraries - Drug Discovery and Development

Sigma-Aldrich and the second phase of The RNAi Consortium (TRC2) have commenced functional validation of the Consortium’s collection of approximately 160,000 previously-cloned lentiviral-based shRNA vector constructs. Currently, more than 5,000 clones have been tested in the functional validation process. Validated clones covering more than 700 genes are available in Sigma-Aldrich’s MISSION shRNA collection, a number expected to grow by 75,000 clones per year through 2011. TRC2 will also generate and validate 150,000 additional clones and utilize its collection of validated shRNA libraries to develop new and improved RNAi screening strategies.

Design and development of TRC libraries is led by the Broad Institute of MIT and Harvard. A key goal of the Consortium is to provide at least two clones with a knockdown level of 70% or greater for every human and mouse gene over the next four years. Research will also center on alternative vector development and improved design, with the possible creation of sub-libraries. Functional validation of these knockdown clones will provide significant time and cost savings to researchers by reducing the number of wells to screen, facilitating improved throughput. The total TRC shRNA collection will eventually comprise 300,000 pre-cloned lentiviral-based shRNA vector constructs targeting the human and mouse genomes.

Sigma-Aldrich’s MISSION shRNA portfolio is the exclusive source for researchers to access TRC and TRC2 shRNA libraries in the plasmid DNA and lentiviral formats. All of the shRNA reagents will be fully functionally validated during phase 2 of The RNAi Consortium. Sigma-Aldrich will also expand its program to promote and educate the research community about the multiple applications of RNAi technology by providing educational tools and forums.

“Sigma-Aldrich is committed to the development of RNAi technology. Through our collaboration with TRC2, we’re producing the most highly validated shRNA libraries available to the research community,” said Dave Smoller, President of Sigma-Aldrich’s Research Biotech Business Unit. “By making these tools available to researchers worldwide, Sigma-Aldrich is facilitating advanced disease and drug discovery research.”

Lentiviral-based shRNA libraries enable researchers to study gene function and disease, both in standard cell lines and recognized difficult cell types such as primary, non-dividing, growth-arrested or terminally differentiated cells. Such cell lines are typically not amenable to standard transfection or genomic integration by other viral delivery systems, but they may be transduced efficiently with lentiviral particles.

“Over the coming years, The RNAi Consortium intends to build upon its successes with shRNA to facilitate loss-of-function genetic screens in mammalian cells,” said David Root, Director of the RNAi Platform ““The existing TRC library has already proven highly effective for systematic viral-delivery RNAi screening. TRC2 will generate significant further improvements to the library and its applications.”

Release Date: May 7, 2008
Source: Sigma-Aldrich