RICHMOND, Calif., January 6 /PRNewswire-FirstCall/ -- Sangamo BioSciences, Inc. (Nasdaq: SGMO) today reported the publication of an article entitled "Repression of Vascular Endothelial Growth Factor A in Glioblastoma Cells Using Engineered Zinc Finger Transcription Factors " in the scientific journal Cancer Research. The article, authored by Dr. Andrew Snowden and his colleagues, is the most recent of several peer-reviewed publications that highlight the potential therapeutic applications and specificity of Sangamo's proprietary gene regulation technology.
"These publications demonstrate the efficacy, singular specificity, versatility and broad applicability of our ZFP TF gene regulation platform," said Edward Lanphier, Sangamo's president and chief executive officer. "We believe that gene regulation using ZFP TFs is a potentially useful therapeutic approach for a wide range of diseases."
The Cancer Research article describes the use of Sangamo's zinc finger DNA-binding protein transcription factors (ZFP TFs) to repress the expression of the vascular endothelial growth factor A (VEGF A) gene in a highly tumorigenic glioblastoma cell line, U87MG. VEGF-A is a potent stimulator of new blood vessel growth, or angiogenesis, a process of critical importance to the progression of certain tumors. Constitutive high-level expression of VEGF A has been seen in a variety of solid tumors including brain cancers such as glioblastomas. For this reason, inhibition of angiogenesis, and specifically VEGF, has been an attractive therapeutic target for the treatment of cancer. The data described in this publication demonstrate that engineered ZFP TFs can potently inhibit the expression of VEGF A in a therapeutically relevant model system. Specifically, after treatment with a ZFP TF repressor, levels of VEGF-A protein expressed by U87MG cells were reduced to levels comparable to those observed in a non-angiogenic cell line.
A second paper published by Sangamo scientist Dr. Victor Bartsevich and colleagues in October 2003, in the scientific journal Stem Cells and entitled "Engineered Zinc Finger Protein for Controlling Stem Cell Fate" describes the use of ZFP TFs to direct the differentiation of stem cells. Stem cells are cells that can self-renew and differentiate into specialized cell types. This property makes them attractive targets for the development of cell-based transplantation therapies for various diseases. The ability to reliably trigger and direct stem cell differentiation is a critical step in their potential therapeutic use. The data published in this article demonstrate, using mouse stem cells, that ZFP TFs can be used to regulate the expression of a critical effector of differentiation, the mouse Oct-4 gene, and that regulation of the Oct-4 gene either up or down has a corresponding effect on differentiation of the cells.
Finally, in October, 2003, Dr. Siyuan Tan and colleagues published an article entitled "Zinc finger protein targeted gene regulation: Genome wide single gene specificity" in the Proceedings of the National Academy of Sciences , USA. The work describes the use of a ZFP TF designed to repress and functionally knockout expression of the endogenous human CHK2 gene, a key regulator of cell cycle progression, DNA repair and cell death. Data are presented that demonstrate that an engineered ZFP TF can abolish CHK2 function and that this effect occurs with single gene specificity. The data demonstrate Sangamo's ability to engineer ZFP TFs capable of potently regulating a single gene.
The complete reference for the papers described is given below. Please contact Elizabeth Wolffe, Ph.D. at Sangamo BioSciences, Inc. for a reprint of any of these articles.
Snowden, A. W. et al. (2003) Cancer Research 63: 8968-8976. Repression of Vascular Endothelial Growth Factor A in Glioblastoma Cells Using Engineered Zinc Finger Transcription Factors.
Bartsevich, V.V., et al. (2003) Stem Cells 21: 632-637. Engineered Zinc Finger Protein for Controlling Stem Cell Fate. Tan, S., et al. (2003) PNAS USA 100: 11997-12002. Zinc finger protein targeted gene regulation: Genomewide single gene specificity.
Sangamo Biosciences, Inc is focused on the research and development of novel transcription factors for therapeutic gene regulation and repair. The company's most advanced therapeutic development program involves the use of transcription factors for the treatment of peripheral arterial disease. Other therapeutic development programs are focused on ischemic heart disease, cancer, neuropathic pain, and monogenic diseases. Sangamo's core competencies enable the engineering of a class of transcription factors known as zinc finger DNA binding proteins (ZFPs). By engineering ZFPs that recognize a specific DNA sequence Sangamo has created ZFP transcription factors (ZFP TFs) that can control gene expression and consequently, cell function. Sangamo is also developing sequence-specific ZFP nucleases (ZFNs) for therapeutic gene correction as a treatment and possible cure for a variety of monogenic diseases such as severe combined immunodeficiency, sickle cell anemia and chronic granulatomous disease. For more information about Sangamo, visit the company's web site at www.sangamo.com or www.expressinglife.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 research and development of novel ZFP TFs, ZFNs and therapeutic applications of Sangamo's ZFP technology platform. Actual results may differ materially from these forward-looking statements due to a number of factors, including technological challenges, Sangamo's ability to develop commercially viable products and technological developments by our 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 10-Q. Sangamo assumes no obligation to update the forward-looking information contained in this press release.
For Sangamo BioSciences Inc.
Elizabeth Wolffe, Ph.D.
Manager, Corporate Communications
Burns McClellan, Inc.
Tricia Morsch (media)
Michelle Levine (investors)
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