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MU researcher Randy Prather continues to receive wide recognition
for his work in animal genetics. Photo courtesy of the College
of Agriculture, Food and Natural Resources
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Science
for a Better Life
Researchers Present Data on First
Cloned, Double Knock-Out Miniature Swine
At the annual meeting of the International
Embryo Transfer Society (IETS) last weekend in Auckland, New Zealand,
Randall Prather, distinguished professor of reproductive biotechnology
at the University of Missouri-Columbia, announced the successful
cloning of the first miniature swine with both copies of a specific
gene “knocked out” of its DNA. The ultimate goal of
this research, which is being conducted in partnership with Immerge
BioTherapeutics, Inc., is to develop a herd of miniature swine
that can be used as a safe source for human transplantation, a
process known as xenotransplantation.
“The fact that we have been able to
clone this particular strain of miniature swine with both copies
of the gene knocked out is a very exciting step for the field
of xenotransplantation,” said Prather, a researcher in MU’s
College of Agriculture, Food
and Natural Resources. “Organs from regular swine are
too large for human transplant, and this particular strain of
miniature swine has been refined for years solely for its potential
use in humans.”
New options for organ sources are desperately
needed to treat the rapidly increasing number of critically ill
people on the transplant waiting list. Currently, more than 80,000
people in the U.S. are on that list. Researchers have targeted
the pig as the best potential candidate for an alternative organ
source because of the similarity between human and pig organs
and the relative ease of breeding pigs. However, the massive rejection
response mounted by the human immune system has been a major hurdle
in this research.
A key player in this rejection process is
the gene that produces a sugar molecule called a-1,3-galactosyltransferase
or GGTA1. When a foreign organ is introduced, human antibodies
attach to the sugar molecule on the surface of pig cells produced
from the action of the GGTA1 molecule, thus killing the organ.
With both copies of this gene eliminated, the antibodies cannot
attach, halting the early rejection process.
Robert Hawley and scientists at Immerge, in
collaboration with Kenth Gustafsson, first identified the gene
that produces GGTA1 and eliminated, or knocked it out, of the
DNA of the miniature swine. This genetic material was then sent
to Prather’s lab, where Liangxue Lai, a research assistant
professor at MU, and colleagues implanted it into an egg that
had its DNA eliminated. The egg was stimulated to begin dividing
and was later implanted into a sow. Prather and Immerge announced
in January 2002 in the journal Science that they had
successfully cloned the world’s first single knock-out miniature
swine. The genetic material from these swine was then re-engineered
with the aim of knocking out the second copy of this critical
gene. These cells were then subjected to another round of nuclear
transfer cloning, leading to the birth of the double knock-out
piglet on Nov. 18, 2002.
In addition to the modified genetics, the
Immerge miniature swine also have other important advantages as
potential transplantation candidates.
“The strain of swine we are working
with seems to be incapable of transmitting Porcine Endogenous
Retrovirus (PERV) to human cells in culture, as we reported in
March 2002 in the Journal of Virology,” said Julia
Greenstein, Ph.D., CEO and President, of Immerge. Unlike other
viruses, which can be eliminated either through breeding or raising
pigs in a clean lab environment, multiple copies of PERV form
part of the normal genomic DNA of pigs and are therefore passed
from one generation to the next. “Although the risk of any
harm posed by PERV to xenotransplant recipients may be purely
theoretical, use of this line of miniature swine would help minimize
this particular risk of this new technology,” Greenstein
said.
The University of Missouri-Columbia has a
long-standing research collaboration with Immerge and BioTransplant
Incorporated in the field of porcine genetic engineering. This
close collaboration has allowed this important research to progress
at an accelerated pace. The current collaboration is supported
by a National Institutes of Health Small Business Innovative Research
grant.
Immerge BioTherapeutics was formed on Sept.
26, 2000, as a joint venture between Novartis Pharma AG and BioTransplant
Incorporated. The company, which began operations on January 2,
2001, focuses its research efforts toward developing therapeutic
applications for xenotransplantation. The name of the company
derives from its use of immunology to address the challenges of
conducting transplants between species.
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Last Update:
November 19, 2007
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