Washington — Scientists have for the first time created genetically altered pigs that lack a gene involved in the body's rejection of transplanted organs, a key advance toward the goal of developing high-tech hogs bearing organs for transplantation into humans.
The work represents the first time that scientists have successfully substituted one entire gene for another in pigs in this case, replacing a gene that typically initiates organ rejection with a defective version of the same gene.
The disabled gene is just one of several that scientists believe they will have to alter, or "knock out," in pigs if the animals are ever to help meet the growing demand for transplantable organs. Even if scientists overcome the many technical challenges posed by cross-species transplantation also known as xenotransplantation many safety and ethics concerns remain unsettled.
But advocates for the fledgling field said they were heartened by the latest feat, which bolsters the feasibility of farm animals serving as organ "donors."
"This was a very important experiment to do. It's very important work," said Fritz Bach, a researcher at Harvard Medical School and a pioneer in the field.
The number of patients needing organ transplants has skyrocketed in recent years, while the number of organs donated for such purposes has grown only slightly. The great disparity between supply and demand, even as medical advances have improved the long-term prospects of transplant recipients, has led doctors and researchers to look beyond the pool of potential human donors to neighboring branches of the mammalian family tree.
Pigs have garnered the most attention as potential sources of organs because they are biologically similar to humans but not so similar as monkeys or apes. Those primates pose problems because they are reservoirs of human diseases.
In the new work, scientists at the University of Missouri-Columbia and Immerge BioTherapeutics Inc. of Charlestown, Mass., used cloning technology and a sophisticated gene-swapping technique to grow pigs carrying a dysfunctional version of a gene called GGTA1. The gene helps pigs make an enzyme that attaches sugar molecules to cells in their bodies.
That sugar construct identifies the cells as "pig cells." When pig cells are transplanted into primates, the primate immune system recognizes them as foreign and violently rejects them.
There is still work to be done before GGTA1 is completely eliminated. Two copies of that gene reside in virtually every cell in a pig's body one from each parent. The latest work knocked out only one copy from each cell, so the cells can still make the enzyme that fosters rejection.
The team hopes to have "double knock-out" pigs in which both GGTA1 genes are replaced born within the next year or so.
A second group of scientists reported Wednesday that they, too, had made pigs lacking one copy of the GGTA1 gene. That work, at PPL Therapeutics in Blacksburg, Va., produced five piglets on Christmas Day.
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