>>RICHMOND, Calif., Jan. 2 /PRNewswire/ -- Sangamo BioSciences, Inc. (Nasdaq: SGMO - news) today announced the publication of results using its engineered zinc finger DNA-binding proteins (ZFPs) to repress expression of a gene required for the development of fat cells (adipogenesis). The paper was published in the January 1, 2002 issue of the journal Genes & Development and is co-authored by scientists from Pfizer Inc (NYSE: PFE - news) and Sangamo.
The data presented in the paper represent a significant advance in the external application and validation of Sangamo's ZFP transcription factor (ZFP-TF) technology, which enables the specific control of genes within an organism. Sangamo ZFP-TFs specifically repressed expression of a gene variant, or isoform, in a mouse cell type that is the precursor to fat cells. Repression of the gene prevented the cells from developing into mature fat cells (adipocytes).
This initial finding led the scientists to further study the role of the gene, known as PPARgamma, in the development of fat cells. In particular, through the use of two ZFP-TFs that bind at slightly different positions on the gene, the scientists for the first time precisely identified the PPARgamma2 isoform as the gene variant critical for fat cell development.
In a commentary published in the same issue of Genes & Development, Mitchell A. Lazar, M.D., Ph.D., Professor of Medicine and Genetics, Chief, Division of Endocrinology, Diabetes and Metabolism and Director, Penn Diabetes Center of the University of Pennsylvania School of Medicine, said, ``... [T]he relative importance of the two PPARgamma isoforms for adipogenesis has remained an open question because PPARgamma1 and PPARgamma2 are expressed at comparable levels in adipocytes. Ren and coworkers have elegantly addressed this question.'' Dr. Delin Ren of Pfizer Global Research and Development is lead author of the paper.
Dr. Lazar also stated in the commentary, ``PPARgamma, a member of the large family of nuclear hormone receptors, has received enormous attention as its role has emerged in the formation of adipose tissue, as well as in the pathogenesis and treatment of diabetes, cardiovascular disease and cancer.'' The data reported in the paper indicate that this application of Sangamo's ZFP technology may improve understanding of these diseases and support the development of potential new treatments.
``The publication of this research is a milestone in demonstrating the enormous potential of gene targeting using ZFP-TFs,'' said Edward Lanphier, Sangamo's chief executive officer and president. ``The data clearly show the precision with which ZFP-TFs can regulate endogenous gene expression, which may lead to the development of novel approaches to the treatment of human disease.''
Zinc finger DNA-binding proteins (ZFPs) are the dominant class of naturally occurring transcription factors in organisms from yeast to humans. Transcription factors, which are found in the nucleus of every cell, bind to DNA to regulate gene expression. The ``designer transcription factors'' made from ZFPs allow precise targeting to a particular gene or genes of interest. Since the over-expression or under-expression of individual genes is the basis for many diseases, the ability to regulate genes with engineered ZFPs has enormous potential therapeutic benefit.<<
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