Miniature Swine May Be Future Organ Donors

In a major achievement that brings scientists closer to making animal-to-human transplantation a reality, miniature swine engineered to avoid rejection in humans have been successfully cloned by researchers from the University of Missouri (Columbia, USA) and Immerge BioTherapeutics Inc. (Charlestown, MA, USA). The research is reported online by the journal Science at the Science Express website (www.sciencexpress.org). Immerge BioTherapeutics is a joint venture of BioTransplant Inc. and Novartis Pharma AG.

Overcoming the human body's massive immune response after perceiving a foreign organ is the greatest challenge in xenotransplantation. The hyperacute rejection occurs when human antibodies attach to sugar molecules on the surface of the transplanted organ's cells. Once they attach, the antibodies kill the cells. In this new line of miniature swine, however, the gene that produces this sugar molecule, called –1,3-galactosyltransferase (GGTA1), was "knocked out” of their DNA. Without the sugar, the antibodies don't attach and the rejection process cannot begin.

The researchers report that this is the first targeted modification of the pig genome and only the second in any large animal. Also, these swine are the first nuclear transfer-derived miniature swine. The researchers have been developing a line of miniature swine that offers advantages for transplantation. One is the organ size, which is appropriate for human recipients. Another advantage is that cells from this line of pigs, in contrast to other cells, have shown they do not have the capacity to spread porcine endogenous retrovirus to human cells in culture.

"We believe this line of miniature swine offers the greatest potential for clinical use in humans, and we're working closely with the University of Missouri-Columbia and our commercial partner, Infigen Inc., to develop these swine with this goal in mind,” said Robert Hawley, Ph.D., associate director of animal genetic engineering at Immerge BioTherapeutics.




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