THE HAGUE, The Netherlands, Sept. 25 /PRNewswire-FirstCall/ -- Sangamo BioSciences, Inc. (Nasdaq: SGMO - News) announced today that Dr. Michael Holmes, Team Leader, Small Molecule Screening, will present data on a novel cell-based screening system to identify drugs that affect signaling pathways. This system, based on the use of engineered zinc finger DNA binding proteins (ZFPs), enables rapid screening of small molecules for their effects on several different signaling pathway targets simultaneously, providing a robust screening platform that yields high information content. The data are being presented at the 8th Annual Meeting of the Society for Biomolecular Screening.
Signaling pathways are the complex networks of biochemical interactions that cells use in order to react to changing conditions in their environment. Some diseases are caused by abnormalities in a signaling pathway. One form of breast cancer, for example, is caused by an increased sensitivity to the hormone estrogen. In this case, estrogen provides a signal that stimulates the cells to grow in an uncontrolled fashion. Drugs that interrupt or restore these damaged pathways have the potential to cure diseases. The pharmaceutical industry makes a significant investment every year in screening programs aimed at identifying molecules that can be used to modify a cell's signaling pathways.
"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, Sangamo's vice president of research. "We have constructed cell lines that allow us to 'multiplex,' i.e. to screen multiple signaling pathways in the same cell at the same time. This allows conservation of precious compound resources while measuring the efficacy of the compounds against several targets simultaneously." Dr. Holmes will be specifically discussing the use of the platform to screen small molecule drugs against nuclear hormone receptors, including estrogen receptor, a target involved in several disease areas including cancer and osteoporosis. "The system is unique," said Dr. Holmes, "in that it is highly adaptable to any number of different diseases and can be applied to a wide range of signaling pathways."
In the cell-based screening system developed by scientists at Sangamo, the native DNA binding domain of the nuclear receptor has been replaced by an engineered ZFP that redirects the function of the receptor to an unrelated gene whose activity can be easily measured.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.
Nuclear receptors are proteins that serve as on-off switches for the expression of certain cellular genes. These switches control reproductive development as well as the development and differentiation of skin, bone and parts of the brain, and are important therapeutic targets for the pharmaceutical industry for a variety of conditions including cancer and diabetes. Nuclear receptors contain a DNA binding domain that allows them to recognize DNA sequences of specific genes and a "ligand" binding domain that controls whether the protein is active or not. When the receptor binds its ligand it becomes active and regulates a specific set of genes. The pharmaceutical industry is actively screening for small molecule compounds that interact with nuclear receptors... |
