Identifying Drugs that Affect Signaling Pathways

A cell-based screening system is designed to identify drugs that affect signaling pathways. Data on the system were presented at the annual meeting of the Society for Biomolecular Screening in The Hague (The Netherlands).

Some diseases are caused by abnormalities in a signaling pathway. Drugs that interrupt or restore these damaged pathways have the potential to cure diseases. The cell-based system, which makes use of engineered zinc finger DNA binding proteins (ZFPs), allows rapid screening of small molecules for their effects on several different signaling pathway targets simultaneously. The system was developed by Sangamo BioSciences, Inc. (Richmond, CA, USA).

In Sangamo's system, the native DNA binding domain of the nuclear receptor has been replaced by an engineered ZFP that redirects the function of the receptor to an unrelated gene whose activity can be easily measured. Several different receptors can be tested within the same cell by fusing them to different ZFPs that redirect them to different endogenous genes. Compounds added to these cells can be evaluated for their ability to either activate or inhibit the function of these receptors.

"The rising cost of drug development means that there is an ever growing need to extract as much information about the relevant properties of candidate pharmaceuticals as early as possible,” said Dr. Casey Case, vice president, research, at Sangamo. "Our system is unique in that it is highly adaptable to any number of different diseases and can be applied to a wide range of signaling pathways.”




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Sangamo BioSciences, Inc