PRESS RELEASE: Sangamo BioSciences and Sigma-Aldrich Announce Nature Biotechnology Study

Sangamo BioSciences and Sigma-Aldrich Announce Nature Biotechnology Study Demonstrating Zinc Finger Technology for Modification of Human Stem Cells

Application of ZFN Technology in Stem Cells has Potential to Yield High Value Research Reagents and Therapeutic Products

ST. LOUIS and RICHMOND, Calif., Oct. 29 -- Sigma-Aldrich Corporation and Sangamo BioSciences, Inc. announced today the publication of data demonstrating the use of Sangamo's ZFP Nucleases (ZFNs) for "gene-editing" in human stem cells. This work represents a significant advance in the ability to specifically and efficiently modify the human genome in stem cells potentially enabling the efficient generation of stem cell lines for use as models of human disease for medical research and for drug testing. In addition to its use in the generation of valuable research reagents, the technology has potential in the therapeutic application of stem cells.

The work, which was carried out in the laboratory of Luigi Naldini, M.D., Ph.D. at the San Raffaele Telethon Institute for Gene Therapy, Milan, Italy, in collaboration with Sangamo scientists, was published in Nature Biotechnology as an advance online publication (http://www.nature.com/ nbt/journal/vaop/ncurrent/abs/nbt1353.html [1]).

"This is a significant advance for both research and the potential therapeutic use of stem cells," stated Dr. Naldini, a senior author of the study. "Stem cells are the body's natural resource for regeneration and repair and the ability to efficiently add a therapeutic gene into the genome of a cell at a predetermined location or to correct a mutated gene in a patient's stem cells may enable us to provide a long term solution for many genetic diseases. The powerful combination of our highly efficient delivery platform and Sangamo's ZFN technology made possible unprecedented gene modification efficiency in these therapeutically important cells".

The data published in the Nature Biotechnology paper demonstrate that ZFN-mediated gene modification can be used to correct both mutations in the IL-2R gamma gene, the defective gene in X-linked severe combined immunodeficiency (X-linked SCID), and to add a therapeutic gene to a pre-determined 'safe-harbor' site in the genome of both human hematopoietic stem cells and human embryonic stem (ES) cells. This putative 'safe-harbor site' was selected by the investigators for its capacity to allow efficient expression of the therapeutic gene and to tolerate an insertion event without adverse effects.

"These data open new avenues for experimental biology, biotechnology and medicine," said Philip Gregory, D.Phil., Sangamo's vice president of research. "This year's Nobel Prize for Medicine recognized the importance of gene targeting, or the site specific manipulation of the mouse genome, which has revolutionized biology and enabled the generation of mouse cell-lines and transgenic mouse models of human disease. However, until now and the development of our ZFN technology, genomes of other species such as humans and plants could not be efficiently modified in a site specific manner. Our ZFN technology enables the specific and targeted modification of any genome of potentially any species and may enable the development not only of potential therapeutics but also human cell lines and transgenic animals bedsides the mouse that may be valuable models of human disease for medical research and drug development."

"This publication represents ground-breaking research in the use of ZFNs and stem cells. Sigma's aim is to enable this kind of cutting-edge science by making innovative technologies available to scientists throughout the world," stated David Smoller, Ph.D., President of Sigma-Aldrich's Research Biotech Unit. "This work demonstrates the specificity and efficiency with which Sangamo's ZFN technology platform can be used to correct and add DNA sequences into the genomes of living cells and is further proof of its power and broad applicability. The ZFN technology has potential applications in the rapid generation of both modified stem cells and somatic cell lines that can be used at multiple stages of disease research and drug development. We expect to have ZFN research reagents similar those used in this publication available to all research scientists in the very near future."

About ZFPs

ZFPs are the dominant class of naturally occurring proteins known as transcription factors and are found in the nucleus of every cell. They bind to DNA to regulate gene expression. Though there are many kinds of transcription factors, only ZFPs are amenable to engineering and precise targeting to a particular gene or genes of interest. By engineering ZFPs that can recognize a specific DNA sequence, Sangamo scientists have created ZFP nucleases or ZFNs(TM) that facilitate efficient and highly specific gene modification and ZFP transcription factors or ZFP TFs(TM) that specifically control gene expression and consequently, cell function. Scientists at Sigma-Aldrich and Sangamo will use ZFNs like precision "surgical instruments" to modify genes in cells and to develop and market ZFP products for broad use in numerous laboratory research reagent applications. Among the anticipated applications are cell lines with enhanced protein production performance, panels of knock-out cell lines for drug discovery, as well as novel stem cell and transgenic animal models.

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 7,800 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 http://www.sigma-aldrich.com [2]

About Sangamo BioSciences, Inc.

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 cancer and 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 http://www.sangamo.com [3].

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. 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 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.