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BREAKTHROUGH IN TRANSGENIC ANIMAL TECHNOLOGY



Agricultural and Consumer Press Service College of Agricultural and Life
Sciences
University of Wisconsin-Madison
440 Henry Mall Research Division, Madison  WI  53706   608-262-1461
For More Information:  Jane Homan  608-643-0152;  Jane_Homan@gala.com

BREAKTHROUGH IN TRANSGENIC ANIMAL TECHNOLOGY

Research reported in the 24 November 1998 edition of the Proceedings of the
National Academy of Sciences may herald a new era in biopharmaceutical
production. Work performed in the laboratory of former University of
Wisconsin-Madison dairy science professor Robert Bremel, and by Gala Design
LLC, a Sauk City, Wis. company, has resulted in breakthrough increases in
the efficiency in the production of transgenic livestock.

Dairy livestock are seen as key players in the production of genetically
engineered protein drugs, such as monoclonal antibodies, hormones, vaccine
proteins and enzymes.  Introducing new genes into the animals allows them
to produce specific pharmaceutical proteins in their milk, from where it
can be extracted as a drug component.  Costs of producing proteins by this
route are far lower than more traditional pharmaceutical production
methods, using large culture vessels or bioreactors.

The PNAS article describes a new method of gene introduction that greatly
increases the efficiency of production of transgenic cattle.  The
transgametic method inserts a gene into the unfertilized oocyte or egg,
which stably incorporates the gene into the maternal germline.  Once the
egg is fertilized, all cells of the resulting embryo carry the new gene,
and the calf is born with the capability to secrete a new protein in milk.
Subsequent generations, offspring of each founder animal, will also carry
the desired gene.

Older, less efficient production methods made transgenic livestock very
costly.  Cloning and pronuclear microinjection typically lead to only 1
percent of animals born carrying the new gene.  The new technology also
sidesteps problems of gene stability and mosaicism seen with
microinjection.  When DNA is microinjected into a fertilized embryo, the
DNA is often not taken up until cell division has occurred.  As a result,
only some cell lineages carry the new gene.  If the germ or sex cells don't
carry the new gene, then the gene isn't reliably transferred to offspring.

The efficiency of the new technology could make cloning and pronuclear
microinjection economically obsolete for many biopharmaceutical purposes.
It also paves the way to applications of biotechnology in agricultural
livestock, similar to those that have changed crop agriculture in recent
years. The technology may also have applications in other mammals.

The scientists believe the technology described also points to a key
process in evolution.  Transposable elements, or transposons, are known to
jump to new locations in the genome (the cell's hereditary material) and
bring about changes in the genome that confer selective advantage.  The
experimental introduction of genes by a vector  - which is structurally
very similar to a transposable element - into the exposed genome of the
oocyte results in uptake of a new, fully heritable, genetic characteristic.

The vectors used build on the work of the late Howard Temin, a UW-Madison
researcher who won a Nobel Prize for his work in describing reverse
transcription, in which RNA is used as a template for copying and inserting
a DNA gene into a cell.

Early steps in the research were performed by Anthony Chan, then a graduate
student in Bremel's lab at the UW-Madison's College of Agricultural and
Life Sciences, and the work was completed by Bremel and colleagues at Gala
Design.  The technology is licensed through the Wisconsin Alumni Research
Foundation, which returns royalty income from university inventions to the
University of Wisconsin.

For more information see www.gala.com or email galainfo@gala.com The
College of Agricultural and Life Sciences at UW-Madison is at
www.cals.wisc.edu/