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Sangamo BioSciences and Sigma-Aldrich Announce Publication of Study Demonstrating Zinc Finger Technology for Rapid Generation of 'Knock-Out' Cell Lines

ZFN Technology has Broad Applications in Research, Drug Development and


ST. LOUIS and RICHMOND, Calif., March 24 /PRNewswire-FirstCall/ -- Sigma-Aldrich Corporation (Nasdaq: SIAL) and Sangamo BioSciences, Inc. (Nasdaq: SGMO) announced today the publication of data demonstrating the use of Sangamo's zinc finger DNA-binding protein nucleases (ZFNs(TM)) in a new approach for rapid generation of "knock-out" cell lines, important tools in research and therapeutic product development.

This work, which was carried out in collaboration with scientists from Pfizer Inc, represents a significant advance in the specificity and efficiency of the generation of cell lines in which an individual gene has been "knocked-out" or deleted. Such cell lines are powerful tools that are widely used in research to identify a gene's function, in drug development to screen potential drug candidates and for production of recombinant proteins. In addition, Sangamo is using this technology to develop ZFP Therapeutics(TM) for the treatment of HIV/AIDS and brain cancer. Sigma-Aldrich is Sangamo's exclusive licensee for this technology in the laboratory research reagent field.

"These data have broad implications for experimental and translational biology, biotechnology and medicine," said Philip Gregory, D.Phil., Sangamo's vice president of research. "The generation of knockouts in basic research and industrial cell line engineering has been severely limited by the absence of efficient methods for the specific, targeted disruption of any gene. Our ZFN technology facilitates this in a rapid, single-step process. Importantly, the process enables the simultaneous disruption of both cellular copies of the gene of interest with an efficiency that obviates the need for selection markers and other complicated strategies to identify knockout cells -- a dramatic improvement over existing methodologies."

The work, co-authored by scientists at Sangamo and Pfizer Inc, was published online on March 21, 2008, in the Early Edition of the Proceedings of the National Academy of Sciences ("Targeted Gene Knockout in Mammalian Cells Using Engineered Zinc Finger Nucleases").

The data demonstrate that ZFN technology can be used to significantly speed up the process of generating cell lines in which a single gene is specifically knocked out. ZFNs were used to place a double strand break in the DNA sequence precisely within the gene to be eliminated. The process then takes advantage of the cell's DNA repair system which repairs the break in the sequence. This natural process often results in a small amount of DNA being deleted at the site of the break and the consequent disruption of the expression of the gene and the protein that it encodes. Sangamo and Pfizer scientists demonstrated that the disruption process occurred with sufficiently high frequency that selection markers were not required to identify multiple independent knockout cell lines with minimal screening effort.

"This publication represents ground-breaking work in the use of ZFNs and highlights an application of this powerful technology that is expected to revolutionize research, drug development, and protein production. Sigma's aim is to make the technology widely available to scientists throughout the world," stated David Smoller, Ph.D., President of Sigma-Aldrich's Research Biotech Unit. "In addition to reagents for knocking out an investigator's 'favorite gene' in a particular cell type, the ZFN platform can be used to generate panels of cell lines for small molecule drug screening in which the 'druggable universe' of gene targets have been individually knocked out. We expect to have ZFN research reagents similar to those used in this publication available to all research scientists in the very near future."

"The applications of this technology are of significant commercial value," said Edward Lanphier, Sangamo's president and CEO. "While the current publication focuses on research and biotechnology applications, we have used these same techniques for knocking out genes in multiple crop plants and to develop ZFP Therapeutics(TM). We are developing potential treatments for HIV/AIDS by knocking-out the CCR5 gene in T-cells and for brain cancer (glioblastoma) by disrupting the glucocorticoid receptor (GR) in engineered killer T-cells. We expect to file Investigative New Drug Applications (INDs) for both of these programs to enter the clinic later this year."

About Sigma-Aldrich

Sigma-Aldrich is a leading Life Science and High Technology company. Our biochemical and organic chemical products and kits are used in scientific and genomic research, biotechnology, pharmaceutical development, the diagnosis of disease and as key components in pharmaceutical and other high technology manufacturing. We have customers in life science companies, university and government institutions, hospitals, and in industry. Over one million scientists and technologists use its products. Sigma-Aldrich operates in 36 countries and has 7,900 employees providing excellent service worldwide. We are committed to Accelerating Customer Success through Leadership in Life Science, High Technology and Service. For more information about Sigma-Aldrich, please visit our award-winning Web site at

About Sangamo

Sangamo BioSciences, Inc. is focused on the research and development of novel DNA-binding proteins for therapeutic gene regulation and modification. The most advanced ZFP Therapeutic(TM) development program is currently in Phase 2 clinical trials for evaluation of safety and clinical effect in patients with diabetic neuropathy. Phase 1 clinical trials are ongoing to evaluate a ZFP Therapeutic for peripheral artery disease. Other therapeutic development programs are focused on stem cell mobilization, ALS, cancer, HIV/AIDS, neuropathic pain, nerve regeneration, Parkinson's disease and monogenic diseases. Sangamo's core competencies enable the engineering of a class of DNA-binding proteins known as zinc finger DNA-binding proteins (ZFPs). By engineering ZFPs that recognize a specific DNA sequence Sangamo has created ZFP transcription factors (ZFP TF(TM)) that can control gene expression and, consequently, cell function. Sangamo is also developing sequence-specific ZFP Nucleases (ZFN(TM)) for gene modification. Sangamo has established strategic partnerships with companies outside of the human therapeutic space including Dow AgroSciences, Sigma-Aldrich Corporation and several companies applying its ZFP Technology to enhance the production of protein pharmaceuticals. For more information about Sangamo, visit the company's web site at

This press release may contain forward-looking statements based on Sigma-Aldrich's and Sangamo's current expectations. These forward-looking statements include, without limitation, references to the research and development of novel ZFNs, and potential therapeutic, medical research and drug development uses of the ZFN technology and the timing of initiation of clinical trials by Sangamo. Actual results may differ materially from these forward-looking statements due to a number of factors, including technological challenges, the ability of Sangamo and Sigma-Aldrich to develop commercially viable products and technological developments by our competitors. See the SEC filings, and in particular, the risk factors described in the Annual Report on Form 10-K and its most recent Quarterly Report on Form 10-Q of each of Sangamo and Sigma-Aldrich. Neither Sigma-Aldrich nor Sangamo assumes any obligation to update the forward-looking information contained in this press release.

SOURCE Sangamo BioSciences, Inc.
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