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Sangamo's Zinc Finger Nuclease Technology Used to Efficiently Modify Human Stem Cells
Date:9/8/2009

RICHMOND, Calif., Sept. 8 /PRNewswire-FirstCall/ -- Scientists from The Whitehead Institute used zinc finger nucleases (ZFNs) designed by Sangamo BioSciences, Inc., (Nasdaq: SGMO) to efficiently and precisely modify the genomes of human embryonic stem cells (hESCs) and induced pluripotent stem cells (hiPSCs). Human ESCs and iPSCs are useful tools in drug discovery and development. Scientists also hope to use these cells therapeutically in transplantation medicine and other regenerative applications. The research was described in a paper which appears in today's issue of the scientific journal Nature Biotechnology.

"The application of ZFN technology to human stem cells opens a new phase in human genetics," said Rudolf Jaenisch, M.D., a member of the Whitehead Institute and Professor of Biology at Massachusetts Institute of Technology (MIT). "In contrast to mouse stem cells which have been easy to modify, it has been very difficult and time-consuming to modify genes in human ESCs and iPSCs. This has severely limited their usefulness for the study of cell differentiation and as models for human disease. The work that our team published in Nature Biotechnology demonstrates that ZFNs enable new, rapid, efficient and specific methods to work with stem cells giving researchers the tools to gain valuable insights into how embryonic stem cells differentiate into adult cells and enabling the generation of patient-specific models of human disease."

Stem cells differ from other cell types in two fundamental ways. First, they are unspecialized cells capable of renewing themselves through cell division. Second, under certain conditions, they can be induced to become tissue- or organ-specific cells with special functions. Stem cells have the potential to develop into the body's many different cell types and in many tissues they serve a repair function, differentiating and replacing damaged cells. iPSCs are adult cells that have been genetically reprogrammed to an embryonic stem cell-like state. An advantage of iPSCs is that they can be derived from the adult cells of a person and will possess the same genetic background as that individual.

"These data are another powerful demonstration of the specificity and broad applicability of Sangamo's ZFP technology across medically and commercially relevant cell types," stated Philip Gregory, D. Phil., Sangamo's chief scientific officer and vice president of research. "The ability to efficiently modify stem cells enables the generation of valuable new tools for drug screening and the study of human disease as well as therapeutic applications in regenerative medicine."

In the article published today, Dr. Jaenisch and his team demonstrated the broad applicability of gene editing applications enabled by ZFNs in hESCs and hiPSCs. In one example, they generated hESCs that carried a reporter gene. This gave researchers a visual method to clearly identify undifferentiated cells from those that had differentiated to their final cell type. In another example they inserted a new gene into a specific site in the genome of hESCs and demonstrated that ZFNs can be used to generate reporter cells in non-expressed genes in the genomes of hESCs and iPSCs, tools that will be useful in the study of cell fate and differentiation protocols.

("Efficient Targeting of Expressed and Silent Genes in Human ESCs and iPSCs Using Zinc Finger Nucleases" D.Hockemeyer, Soldner, F., Beard, C., Gao, Q., Mitalipova, M., DeKelver, R. C., Katibah, G.E., Amora, R., Boydston, E.A., Zeitler, B., Meng, X., Miller, J.C., Zhang, L., Rebar, E.J., Gregory, P.D, Urnov, F.D., and Jaenisch, R. Nature Biotechnology (2009) Vol 27:September)

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 and ALS. Sangamo also has a Phase 1 clinical trial to evaluate safety and clinical effect of a ZFP Therapeutic approach for the treatment of HIV/AIDS. Other therapeutic development programs are focused on cancer, 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) that can control gene expression and, consequently, cell function. Sangamo also is developing sequence-specific ZFP Nucleases (ZFN) for gene modification. Sangamo has established strategic partnerships with companies in non-therapeutic applications of its technology including Dow AgroSciences, Sigma-Aldrich Corporation and several companies applying its ZFP technology to engineer cell lines for the production of protein pharmaceuticals. For more information about Sangamo, visit the company's web site at www.sangamo.com.

This press release may contain forward-looking statements based on Sangamo's current expectations. These forward-looking statements include, without limitation, references to the application of Sangamo's 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 its partners to develop commercially viable products and technological developments by Sangamo's competitors. See the company's SEC filings, and in particular, the risk factors described in the company's Annual Report on Form 10-K and its most recent quarterly report on Form 10-Q. Sangamo assumes no obligation to update the forward-looking information contained in this press release.


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