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Genetically Engineered Pigs May Provide Quantities of Rare Anti-Clot Agent : Medicine: If it proves a match with the substance found in human blood, it could be used to help heart attack, stroke and surgery patients.

April 08, 1992|THOMAS H. MAUGH II | TIMES SCIENCE WRITER

SAN FRANCISCO — Researchers have created a valuable new source of a promising anti-clotting agent called Protein C by genetically engineering pigs to produce the protein in their milk.

Animal studies hint that Protein C has great potential for preventing the formation of clots in heart attack and stroke victims, in patients undergoing hip replacements and other major surgery and in victims of septic shock caused by bacterial infections.

But researchers have been limited in their ability to test Protein C in people because they can isolate only very small quantities from human blood, where it is present in only trace amounts.

It is hoped that the work with pigs will solve that problem by providing a large supply of Protein C, which the researchers believe--based on previous successes in producing other human proteins in animals--will be identical to the protein found naturally in humans.

The protein is far too complex to be produced in bacteria or yeast, which are the mainstays of the genetic engineering industry. But the pigs produce it readily in their milk and at concentrations high enough to permit easy purification, biochemical engineer William Velander of Virginia Polytechnic Institute and State University said here Monday at a meeting of the American Chemical Society.

Velander's work is "extremely significant" because it should make much larger quantities of Protein C available for testing, said molecular biologist William Drohan of the American Red Cross in Rockville, Md.

The results are also important because Protein C is only the fourth therapeutic protein produced in the milk of farm animals, such as goats and sheep, and is the largest and most complex. Other products that have been produced in animals are the clot-busting agent tPA, a drug for the lungs called alpha-one antitrypsin and human hemoglobin. The growing use of this technique of genetic "pharming" has the potential to make genetically engineered proteins available at lower prices.

For example, tPA costs about $2,000 per dose when produced in bacteria. Genzyme Corp. has developed goats that produce it in their milk and the company estimates that its price could be as low as $100 per dose.

The fact that such a complex molecule as human Protein C can be produced in the animals' milk also makes researchers confident that a variety of other desirable pharmaceuticals can be produced in this fashion as well.

Protein C is a recently discovered agent that shuts down the body's blood-clotting process at two key points in the complex cascade of events that are necessary for a clot to form. It is much more specific than synthetic anti-clotting drugs like warfarin and thus less likely to have undesirable side effects.

Velander took the human gene for Protein C and attached it to genetic "switches," isolated from mice, that signal for the protein to be produced only in milk. He then inserted the altered gene into freshly fertilized pig eggs.

Many of the female pigs that received the gene then began producing the protein in their milk when they matured. The gene has been passed on to their offspring, Velander said, but none are yet old enough to begin producing milk themselves.

Velander and his colleagues used conventional techniques to purify the protein and are now studying it to ensure that it is identical to the natural human protein. He has not reported the results of that comparison yet, but said he is confident the protein will be identical.

Velander noted that a small group of pigs could produce many kilograms of Protein C per year. By contrast, Drohan noted that even if the Red Cross isolated the drug from all the blood it processes each year, a tedious and expensive procedure, they would only get about 10 kilograms.

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