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US researchers successfully clone first knockout miniature swine

Study Represents Important Step Towards Animal-to-Human Organ Transplantation

Columbia, MO, January 3, 2002 Researchers from the University of Missouri-Columbia and Immerge BioTherapeutics Inc. (a BioTransplant Incorporated (Nasdaq:BTRN)/Novartis Pharma AG (NYSE:NYS) joint venture company) reported they have successfully cloned the worlds first miniature swine with a specific gene "knocked out" of their DNA. This particular knockout moves scientists closer to making animal-to-human organ transplantation a reality, offering additional hope to the more than 75,000 Americans currently awaiting organs, 16 of whom die each day while waiting. The study is reported online by the journal Science at the Science Express web site (www.sciencexpress.org).

"The greatest challenge in xenotransplantation or the transplanting of a cell, tissue or organ from one species to another is overcoming the bodys massive immune response after it perceives a foreign organ," said Randall Prather, Ph.D., MU Distinguished Professor of Reproductive Biotechnology. This modification eliminates the gene that triggers this response, opening the door for further advances.

The aggressive (hyperacute) rejection response seen in previous research occurs when human antibodies attach to sugar molecules on the surface of the transplanted pig organs cells. Once they attach, the antibodies kill the cells. In this particular line of miniature swine, however, the gene that produces this sugar molecule, called -1,3-galactosyltransferase or GGTA1, has been eliminated. Without the sugar, the antibodies cant attach, and therefore the rejection process cant begin.

Todays report represents the first targeted modification of the pig genome and only the second in any large animal. It also is the first nuclear transfer-derived miniature swine. The choice of pig line is another unique feature of this study and represents advan
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Contact: Susan Hayes
shayes@porternovelli.com
212-601-8000
Porter Novelli
3-Jan-2002


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