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Cooperative Extension Service Communications and Technology Department 3354 1000 E. University Ave. Laramie, WY 82071 (307) 766-6342 • fax (307) 766-3998 • www.uwyo.edu |
For Immediate Release
Story Contact:
Don Jarvis: (307) 766-4282
Contact: Steven L. Miller, Senior Editor
Phone: (307) 766-6342
E-mail: slmiller@uwyo.edu
Archived News Site www.uwyo.edu/agadmin/news/news.htm
Date: June 12, 2006
UW molecular biologist harnesses caterpillars to produce ‘humanized’ proteins
Sometimes, 1+1 CAN equal 3.
Or, at least with Department of Molecular Biology Professor Don Jarvis and his colleagues in the College of Agriculture at the University of Wyoming, things can add up that bend reality: insect + mammalian = mammalian.
The eventual solution to the above equation is caterpillars blended in a vat to produce caterpillar goo for the extraction of a specific, medically beneficial protein.
With a dash of genetic engineering and sprinkling of old-fashioned biology, Jarvis and colleagues have used baculoviruses – viruses that infect insects – and their insect hosts to produce recombinant (genetic material resulting from the splicing of DNA fragments) glycoproteins. Further, they have genetically modified certain protein production pathways in insect cells with mammalian genes.
The result is a protein palatable to humans.
The recombinant baculovirus is used to infect the genetically modified insect cells, causing mass production of a desired protein. “The insect cells become bioreactors,” said Jarvis, who began as an associate professor at UW in 1998 and became a professor in 2000.
Additional genetic modifications of the insect cells or insects that serve as hosts for recombinant baculoviruses are necessary to equip glycoproteins with the correct “humanized” sugars and to eliminate a fly-in-the-ointment, in the form of certain sugars that can bug humans with allergic reactions.
Jarvis noted it is the sugar moieties, or parts, of certain glycoproteins that are largely responsible for human allergenic responses to bee and wasp stings.
There are other reasons why scientists look to the insect world for protein manufacturing. Large amounts can be created by insect cells, and they can be grown economically.
The protein products can be used in real-world applications, such as testing for hypothyroidism in dogs. The use of a recombinant product circumvents potential exposure of companion animals to contaminating prions (an infectious particle of protein) associated with bovine spongiform encephalopathy (BSE) also known as “mad cow disease.”
“The best way to test for hypothyroidism had been to challenge companion animals with thyroid stimulating hormone (TSH) purified from bovine pituitary glands. Due to the potential danger of transmitting BSE to these animals, it would be unethical to inject a dog with TSH isolated from bovine pituitaries,” he said.
A new test could use TSH produced by the insect production system, and a patent application has been filed for this new process.
Jarvis and the University of Wyoming also have patents pending on a protein production system process involving caterpillars. Together with colleagues at Chesapeake PERL, a protein manufacturing company in Maryland, and the University of Notre Dame, Jarvis is developing a process for the production of humanized recombinant glycoproteins in baculovirus-infected caterpillars.
Together, this group received a $2.5 million, three-year National Institute of Standards and Technology's Advanced Technology Program grant to genetically transform caterpillars to produce humanized glycoproteins.
The caterpillars with genetically modified protein glycosylation pathways are called Transpillars ™.
“Chesapeake PERL cultivates a million caterpillars a week,” Jarvis noted. The caterpillars are raised individually in what look like ice cube trays. The Transpillars™ are fed a recombinant baculovirus encoding a glycoprotein of interest, become infected, and begin producing the required glycoprotein product.
The critters are ready for processing at about three to five days after being infected. At this point, they contain large amounts of the recombinant glycoprotein product. But, if infected for too long, the baculovirus turns the caterpillars into useless mush.
“The infected caterpillars are put in a vat and homogenized, and then the protein is purified by conventional biochemical methods,” said Jarvis.
It sounds like a strange source of protein, but one has to distinguish the process from the product, he said. Product quality and cost are the most important issues, and the baculovirus-caterpillar system is much cheaper than most.
“Also, PERL has caterpillars ready to go at the drop of a hat, so if there is a demand for something really fast, it could be produced very quickly in this system,” he noted.
Jarvis says the insect protein production system can be a tool to help fulfill world demand. “We don’t have the manufacturing capacity for everything that needs to be made by the biotechnology industry,” he said. “Demand for recombinant proteins has already exceeded worldwide production capacity, and this problem is going to get much worse as new protein drugs come out of the pipeline.”
On the Web: http://www.uwyo.edu/MolecBio/Jarvis.htm
http://www.erc.umd.edu/TAP/Chesapeake_PERL/home.html
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