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Making Pigs More Like People

3 January 2002 (All day)
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Handling rejection. This piglet lacks one copy of a sugar-producing gene that makes humans reject pig organs.

Ever since the cloning of Dolly the sheep, transplant scientists have hoped for a way to create a line of identical animals genetically engineered so their organs could be used in people. Now, researchers report a major advance that brings that goal closer--the creation of four cloned piglets that lack one copy of a gene that causes pig organs to be rejected by the human immune system. The finding is reported in a paper published online today by Science.

Pigs are the most promising species for organ transplants because they are physiologically similar to humans and in plentiful supply. But progress in the field has been slow, in part because transplanted organs will almost certainly be rejected by the human body. Pigs produce a particular sugar on the surface of their endothelial cells that primates' immune systems recognize as foreign. As a result, they attack the pig cells, leading to organ failure. The only complete solution is thought to be a pig lacking the gene for ?-1,3-galactosyltransferase, the enzyme that makes the sugar.

Now, animal scientist Randall Prather and his team at the University of Missouri, Columbia, along with collaborators at Immerge BioTherapeutics Inc. in Charlestown, Massachusetts, have knocked out the galtransferase gene in fetal cells used to make cloned piglets. The researchers fused the modified fetal cells with oocytes from which the chromosomes had been removed. They implanted more than 3000 of the resulting embryos into 28 surrogate mother sows. Seven transgenic piglets were born in September and October, of which four survived. The four, all females, still make the sugar with their good copy of galtransferase; Prather says the next step is to produce double knockout pigs, most likely using conventional breeding methods. Still, "this is something that's been eagerly awaited," says immunologist Jeffrey Platt of the Mayo Clinic in Rochester, Minnesota.

Other companies are hot on the Missouri team's heels. Scotland-based PPL Therapeutics announced on 2 January that five pigs with the knockout allele were born on Christmas Day. The announcement appeared to scoop Prather's paper, which was embargoed until today, but the PPL results have not been published yet. David Ayares of PPL's lab in Blacksburg, Virginia, defends the company's decision to issue a press release, noting that it must by law inform stockholders promptly of information that could affect its stock price. Announcing results by press release is "becoming the norm in the biotech industry," Ayares says. The news sent PPL's stock soaring 46% on the London stock exchange.

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