MADISON - Research reported in the November 24 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 of 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 rel
Contact: Jane Homan
University of Wisconsin-Madison