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Iowa State plant scientists tweak their biopharmaceutical corn research project

June 26, 2006

AMES, Iowa — A biopharmaceutical corn created at Iowa State University is getting a makeover. Researchers are developing the corn into a variety that keeps the therapeutic protein, but eliminates the pollen. And they're using traditional breeding to do it.

ISU researchers have had promising results using the biopharmaceutical corn to treat bacterial diarrhea in pigs.

Now they are shifting their focus. They are developing a male sterile corn that carries the transgene. Because male sterile corn plants do not produce pollen, the new biopharmaceutical variety could be grown in corn-producing states without risk of pollinating traditional corn varieties.

"Pollen movement is the issue," said Kendall Lamkey, interim chair of agronomy and Pioneer Distinguished Chair in Maize Breeding. "And that's the most controllable part of the corn production system."

Lamkey, who also directs the Raymond F. Baker Center for Plant Breeding, leads the breeding portion of the research. Kan Wang, the principal researcher, who successfully transformed the corn, is professor of agronomy and director of the Center for Plant Transformation. Both centers are part of Iowa State's Plant Sciences Institute, which initiated the research. The ongoing project is supported by the institute and the College of Agriculture.

Lamkey and Wang say it will take about five growing seasons to make all the breeding crosses needed. The first season took place last winter in the Plant Sciences Institute's Roy J. Carver Co-Laboratory biosafe greenhouse. The biopharmaceutical corn was crossed with the non-transgenic, male-fertile corn line to produce a transgenic F1 hybrid.

Seeds from that cross are being used this summer in a field trial on remote land owned by Iowa State.

The breeding process in the field trial will not shed transgenic pollen. The transgenic crop will be detasseled. It will be surrounded by rows of non-transgenic corn, which will pollinate the detasseled transgenic plants.

Iowa State received permit approval from the U.S. Department of Agriculture's Animal and Plant Health Inspection Service (APHIS) and from the state for the research.

The research plot is located on less than one-half acre of university land in Marshall county. It is about a half mile away from and was planted 28 days later than the nearest commercial corn. A fence will keep out wildlife. The research exceeds APHIS requirements for field trials of regulated plants.

The seed harvested in the fall will be used in the winter again in the high containment greenhouse. Another field trial is expected to take place next summer.

The 2006 field trial is the latest in a series of transgenic corn experiments led by Iowa State researchers. All have received federal and state approval. The trials have taken place three times in Iowa and once in Colorado.

The research is part of Iowa State's work to evaluate the safe use of plants for the production of proteins for pharmaceuticals and industrial products.

Wang engineered the corn to produce LT-B, a protein subunit produced by some strains of E. coli. Research has shown the ability of the protein to stimulate protective immune antibodies. Other Iowa State scientists have been evaluating grain from previous years' studies to understand how the corn-based pharmaceutical can help protect livestock from bacterial infections.

The system being developed in corn will work with other proteins. Corn is the preferred plant for producing proteins for non-food products.

"It's so easy to manipulate from a breeding perspective, and the pollen can be controlled," Lamkey said. "You can't control the pollen easily in self-pollinating crops like soybeans."

"And from a molecular biology and biochemistry point of view, we know so much about corn," Wang said. "Corn seed is such a good reservoir for foreign protein. And the grain, from a pharmacological standpoint, is the grain best tolerated by humans and animals both. Almost nobody is allergic to corn protein."

Lamkey said Iowa State is uniquely qualified to pursue this research because of access to germplasm and "not many places have the genetic transformation capabilities that Iowa State has."

Lamkey and Wang are considering breeding the transgene into a higher yielding, better seed producing, transformable corn inbred line.

"The line that has been used for this corn is really hard to work with in terms of pollination and seed production. It was bred for the purpose of transformation not the field," Lamkey said.

"The best part of this project is that finally conventional breeders like me are now working with molecular biologists like Dr. Wang," Lamkey said. "We're trying to get something that's mutually beneficial. This hasn't happened enough in the public sector."

Iowa State University