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Cloned Pigs Modified for Use in Human Transplants
Bijal P. Trivedi
National Geographic Today
January 3, 2002
Two competing teams have cloned pigs that have been genetically modified
to produce organs more suitable for transplantation into
humans.
Pig organs are well suited for transplantation; they are
approximately the same size as human organs and have similar plumbing,
which makes reconnecting blood vessels much easier. Also, the size of
pig litters tends to be large and pigs reproduce quickly, raising the
prospect of a large supply of "spare" organs.
A problem with using pig organs, however, is that they are coated with
sugar molecules that trigger acute rejection in people. Human antibodies attach
themselves to these sugar molecules and quickly destroy the newly transplanted
pig organ.
To circumvent the rejection, scientists are working to produce pigs that
lack the sugar-producing gene.
In a significant step toward that goal, a team of scientists led by
Randall Prather of the University of Missouri in Columbia created four cloned
piglets in which one copy of the sugar-producing gene was "knocked out" (an
organism receives two copies of a gene, one from the mother and one from the
father). The piglets were born in September and October. A description of the
work was published online by the journal Science.
Earlier this week, PPL Therapeutics PLC of Scotland, the company that
helped clone Dolly the sheep, announced the birth of five cloned piglets that
also lack a copy of the sugar-producing gene. The piglets were born December 25
and were named Noel, Angel, Star, Joy, and Mary.
By selectively breeding the experimental pigs, both teams of scientists
hope to produce pigs lacking both copies of the gene. It's expected that the
organs of these modified pigs could be transplanted into people without the
problem of tissue rejection.
The new results are a significant advance over many other attempts at
genetic modification in animals because in both of the studies, the scientists
were able to modify-in this case, "knock out"-a gene at a specific location.
Although genes from other organisms have been inserted into the genomes of
sheep, cattle, and pigs, scientists have had little control over where on a
chromosome the new gene is incorporated.
"This is the first time a specific genetic modification has been made in
the pig," said Prather.
Prather's team at the University of Missouri and his colleagues at
Immerge BioTherapeutics Inc. in Charlestown, Massachusetts, genetically altered
fetal pig cells, which were used to create embryo clones. Of 3,000 genetically
modified pig embryos that were implanted into 28 surrogate sows, only seven
piglets were born, three of which died later.
The cloning of Dolly almost five years ago raised expectations of
creating identical, genetically modified organs for transplantation into
humans. The cloning of genetically modified piglets brings scientists closer to
their goal of "xenotransplantation"-the transfer of cells and organs from one
species into another.
A concern that has dampened the prospects of xenotransplantation is the
possibility of spreading viruses from one species to another. Porcine
endogenous retrovirus (PERV), for example, is part of a pig's natural genetic
makeup and does not cause any disease in the animal. There is no guarantee,
however, that PERV would be harmless in humans.
To minimize the risk of spreading PERV, Prather's team used a line of
pig-miniature swine-that was developed specifically for the purpose of
transplantation. A major advantage of these pigs is that they are unable to
spread PERV.
Prather's team expects to produce a miniature swine that lacks both
copies of the sugar-producing gene within the next 18 months.
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