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Announces First-Ever 'Functional Map' Linking Genes to Biological Activity in a Vertebrate
Accomplishment Is Result of Largest Vertebrate Genetic Screening Project Ever Conducted
SOUTH SAN FRANCISCO, Calif. and COLOGNE, Germany, Jun 6, 2001 /PRNewswire via COMTEX/ -- For the first time ever, scientists have functionally identified the majority of essential genes involved in the structure and function of the heart, bone, cartilage, blood vessels and nervous system of a vertebrate -- a discovery that could one day lead to new drugs based on an understanding of those genes.
Exelixis, Inc. (Nasdaq: EXEL chart, msgs) made the announcement after the completion of the largest vertebrate genetic screening project ever conducted. Called the Tuebingen 2000 Screen, the project was conducted by Exelixis' recently acquired subsidiary, Artemis Pharmaceuticals GmbH in collaboration with the Max-Planck-Institute of Developmental Biology. While scientists have recently identified the sequence of virtually all of the genes in humans, they have yet to fully understand which genes are linked to the formation of various organ systems as well as the molecular mechanisms underlying disease processes.
"Genomic sequencing and other classical genomics technologies have identified genes and proteins, and have established some aspects of their function. The Tuebingen large scale systematic and comprehensive genetic screens link genes, for the first time, to an actual biological function like organ formation, or patho-physiological process such as cardiac arrhythmias," said George A. Scangos, Ph.D., president and chief executive officer of Exelixis. "The next step for Exelixis and Artemis is to see which of these genes are most likely to respond to new drugs to treat diseases related to the heart, bone, blood vessels, immune and nervous systems."
The Tuebingen 2000 Screen
The Tuebingen 2000 Screen is the largest vertebrate genetic screening project ever conducted. More than 10 million zebrafish were examined for mutations affecting several organs and systems. The size of the screen makes it likely that every essential gene in the genome was analyzed several times. More than 6,500 fish were identified with alterations in the heart, blood, blood vessels, bone, cartilage, nervous system and immune system. As a result, for the first time in a vertebrate, it is possible to systematically analyze every gene for its impact on organ structure and function as well as important disease processes.
Zebrafish were selected for their ease of manipulation, short life cycle and high degree of genetic conservation with humans. The availability of the completed human genome coupled with the ongoing sequencing of several other organisms facilitates the ready translation of genetic information from zebrafish to man. Zebrafish are also uniquely suited for experimental study as they produce large broods of transparent embryos that develop outside the parent, and advance from fertilized egg to fully formed fish in a few days. These characteristics enable researchers to observe developmental processes as they occur, offering critical advantages when studying the development of organ systems such as bone and the cardiovascular system.
The completion of the Tuebingen 2000 screen also draws into focus a number of additional important public investments that will further enhance the value of the zebrafish as a model genetic system. For example, the Sanger Center (UK) recently began an effort to sequence the zebrafish genome and is already putting this information into the public databases. That effort, combined with the ongoing investment by the National Institutes of Health and other European funding agencies is resulting in a unique alignment of genomic, genetic and biological tools.
Peter J.W. Stadler, Ph.D., managing director of Artemis stated, "We anticipate that this study will generate a better understanding of the relationships between genes, organ formation and disease processes which has been difficult to accomplish on a global or comprehensive basis using alternative approaches. This is a landmark achievement for the pharmaceutical industry that allows us to establish the linkage between gene and biological function." Dr. Stadler added, "In addition to the current laboratory methods available to study zebrafish, Exelixis recently licensed a very interesting 'morpholino antisense' technology that allows us to identify the function of a specific gene in less than three days as opposed to the six to nine months that it would take in a mouse."
Because information from DNA sequences alone does not establish the link of a gene to a biological function, Artemis focused the Tuebingen 2000 Screen project on a genetics approach that helps to establish the function of genes critical to a number of human diseases. This "Function First" approach uncovers the biological function of relevant genes even before the sequence is identified. As a result, these functionally validated genes will be used as screening targets for identifying small molecule therapeutics. In addition, the protein products of the genes may be used directly as new therapeutic proteins or as targets for therapeutic antibodies.
Nobel Laureate Professor Christiane Nuesslein-Volhard, a co-founder of Artemis and director of the Max-Planck-Institute for Developmental Biology, initiated the international program in April 2000. The Tuebingen 2000 Screen brought scientists from five world-renowned academic institutions together with scientists at Artemis. In Germany, the institutions included the Max-Planck-Institute for Developmental Biology, Tuebingen; the Max-Planck-Institute for Immune Biology, Freiburg; and the University of Heidelberg. Also participating in the project were the Howard Hughes Medical Institute at the Children's Hospital in Boston, Mass., in the United States and University College in London, United Kingdom.
About Exelixis
Exelixis, Inc. is a leading genomics-based drug discovery company focused on product development through its expertise in comparative genomics and model system genetics. These technologies provide a rapid, efficient and cost effective way to move from DNA sequence data to knowledge about the function of genes and the proteins they encode. Located in Cologne, Germany, Artemis Pharmaceuticals GmbH is focused on the use of vertebrate model genetic systems such as mice and zebrafish as tools for drug discovery. Exelixis acquired Artemis in April 2001, in order to expand its access to vertebrate model system technologies. The company's technology is broadly applicable to all life sciences industries including pharmaceutical, diagnostic, agricultural biotechnology and animal health. Exelixis has partnerships with Aventis, Bayer, Bristol-Myers Squibb, Pharmacia, Protein Design Labs and Dow AgroSciences and is building its internal development program in the area of oncology. For more information, please visit the company's web site at www.exelixis.com.
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