- The Washington Times - Friday, January 4, 2002

In what researchers say is a major step toward an unlimited supply of human transplant organs, scientists have cloned piglets lacking one of the two genes that prompt the human immune system to reject swine tissue.
Researchers said the achievement, announced by two competing labs, advances the day when herds of special swine could be used to grow lifesaving replacement organs for humans with ailing hearts, kidneys, livers and lungs.
"For the field of xenotransplantation [transferring an organ from one species to another], it is a very important advance," Dr. Jeffrey L. Platt, head of transplantation biology at the Mayo Clinic in Rochester, Minn., said on Wednesday. "It is not the final hurdle, but it is very important."
Both teams of researchers reported that they had removed one copy of a pair of genes that puts on the surface of pig cells a sugar called alpha-1-galactose, or alpha-gal, that is attacked powerfully by the human immune system.
For this reason, pig organs transplanted into humans would be killed within hours, researchers say.
One copy of the alpha-gal gene, called GGTA1, was removed from the cloned pigs, but the researchers said it would take more work to create true "knockout" pigs animals with both copies of GGTA1 removed.
A team led by researchers at the University of Missouri, Columbia, and at Immerge BioTherapeutics Inc. of Charlestown, Mass., reported they cloned four piglets lacking a GGTA1 copy. Their study appeared yesterday in Science Express, the online version of the journal Science.
A team at PPL Therapeutics Inc. of Blacksburg, Va., announced Wednesday they had cloned five piglets with just one GGTA1 copy.
The cloned piglets from both teams are all female.
Dr. Randall S. Prather, leader of the Missouri team, said the next step will be to use ordinary breeding techniques to produce pigs that lack both the GGTA1 genes.
"Once you have the one gene out, you can use conventional breeding to make more 'knockout' animals," said Dr. Prather, lead author of the Science study. "Hopefully we will get males in the next generation."
Dr. Prather said the miniature swine used in the study are a scientifically developed strain that has been highly interbred for decades. This means the brothers and sisters can be reliably mated to produce offspring with special genetic characteristics.
David L. Ayares, vice president of research for PPL Therapeutics, said his team already has mother pigs pregnant with males that carry a single copy of the GGTA1 gene. He said these animals will be born later this year and then mated with the females that were born on Christmas Day.
If both parents lack one copy of the GGTA1 gene, there is a one-in-four chance that one of their offspring will have no copies of the gene, Mr. Ayares said.
PPL is a subsidiary of PPL Therapeutics in Scotland that in 1997 helped clone Dolly, the sheep that was the first mammal to be cloned from adult cells.
Julia L. Greenstein, lead researcher at Immerge BioTherapeutics, said the technique gave one chance in 5 million of knocking out one of the gene copies when there were two, but the odds are even longer trying to remove the remaining copy.
"It was one in 5 million when we had two targets," she said. "Now we've got to be twice as good to get the other one."
Miss Greenstein and Mr. Ayares said that in addition to following a breeding program, their respective teams are working to develop cloning cells with both of the GGTA1 genes knocked out.

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