Technology evaluation: SAGE, Genzyme molecular oncology.
Genzyme Molecular Oncology (GMO) is using its SAGE (Serial Analysis of Gene Expression) combinatorial chemistry technology to screen compound libraries. SAGE is a high-throughput, high-efficiency method to simultaneously detect and measure the expression levels of genes expressed in a cell at a given time, including rare genes. SAGE can be used in a wide variety of applications to identify disease-related genes, to analyze the effect of drugs on tissues and to provide insights into disease pathways. It works by isolating short fragments of genetic information from the expressed genes that are present in the cell being studied. These short sequences, called SAGE tags, are linked together for efficient sequencing. The sequence data are then analyzed to identify each gene expressed in the cell and the levels at which each gene is expressed. This information forms a library that can be used to analyze the differences in gene expression between cells [293437]. By December 1999, GMO had identified a set of 40 genes from 3.5 million transcripts that were expressed at elevated levels in all cancer tissue but not seen in normal tissue. The company hope these may provide diagnostic markers or therapeutic targets. The studies also provided data furthering the understanding of the way cells use their genome [349968]. GMO has signed a collaborative agreement with the National Cancer Institute (NCI) to search for new drug candidates in the field of cancer chemotherapy. The collaboration combines GMO's SAGE technology with the NCI's extensive array of 60 cell-based cancer screens. Under the agreement, the NCI will evaluate Genzyme's library consisting of one million compounds against selected cancer screens to identify compounds with anticancer properties [255082]. Xenometrix granted a license agreement for gene expression profiling to GMO in February 1999, giving company access to claims covered in issued US and European patents. The license is non-exclusive and covers the collection of gene expression profiles utilizing all methods including high-density microarrays [315329]. Ontogeny (now Curis Inc) and GMO have entered into a collaboration to study genes for the potential discovery of therapeutic products. GMO will use its SAGE technology to produce libraries of RNA supplied by Ontogeny. The libraries will be put through Ontogeny's screening program [279417]. Under an agreement made in August 1998, Bayer will use SAGE technology to identify genes and thus potential therapeutics [317452]. GMO and Hexagen signed an agreement in March 1998 on the use of SAGE technology in Hexagen's disease gene discovery programs. The first phase of the collaboration will focus on the use of SAGE in studies within Hexagen's type II diabetes gene discovery program. Hexagen has designed these studies to discover susceptibility genes for diabetes and to provide gene expression information for genes associated with type II diabetes [280012]. GMO signed a five-year agreement with Johns Hopkins University School of Medicine (JHU) in July 1997 for research leading to the identification of cancer-related genes. Under the terms of the agreement, JHU researchers will use the SAGE technology to identify and analyze gene expression in cancer. The power of SAGE in finding rare genes was confirmed in a study of gastrointestinal cancer by JHU researchers published in the May 27, 1997 issue of Science. The study showed that of almost 50,000 genes expressed in normal gastrointestinal cells and gastrointestinal tumor cells, 86% of the genes were present at five or fewer copies per cell. Only 51% of those low-abundancy genes were recorded in the GenBank database of known genes in the human genome [257128].
Bartlett
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University of Glasgow Department of Surgery, Level 2, Queen Elizabeth Building, Glasgow Royal Infirmary, Glasgow, G31 2ER, UK. gqva20@udcf.gla.ac.uk
D001709:Biotechnology; D019295:Computational Biology; D020224:Expressed Sequence Tags; D020869:Gene Expression Profiling / Q000379:methods*; D006801:Humans; D009369:Neoplasms / Q000235:genetics*; D016133:Polymerase Chain Reaction