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Biologists engineer algae to make complex anti-cancer 'designer' drug
Date:12/10/2012

yfield. "First, we make this as a single protein with the antibody and toxin domains fused together in a single gene, so we only have to purify it one time. And second, because we make this in algae rather than CHO cells, we get an enormous cost advantage on the production of the protein."

The fusion protein the researchers in his laboratory produced from algae is identical to one that is under development by pharmaceutical companies with a proposed cost of more than $100,000. This same protein could be produced in algae for a fraction of that price, they report in their paper. And the UCSD researchersMiller Tran, Christina Van, Dan Barrera and Jack Bui at the UC San Diego Medical Schoolconfirmed that the compound worked like the more expensive treatment: it homed in on cancer cells and inhibited the development of tumors in laboratory mice.

Mayfield said such a fusion protein could not have been produced in a mammalian CHO cell, because the toxin would have killed it. But because the protein was produced in the algae's chloroplaststhe part of algal and plant cells where photosynthesis takes placeit did not kill the algae.

"The protein was sequestered inside the chloroplast," Mayfield said. "And the chloroplast has different proteins from the rest of the cell, and these are not affected by the toxin. If the protein we made were to leak out of the chloroplast, it would have killed the cell. So it's amazing to think that not one molecule leaked out of the chloroplasts. There are literally thousands of copies of that protein inside the chloroplasts and not one of them leaked out."

Mayfield said producing this particular fusion protein was fairly straightforward because it involved fusing two domainsone to recognize and bind to cancer cells and another to kill them. But in the future, he suspects this same method could be used to engineer algae to produce more complex proteins with multiple domains.

"Can we string together four or five domains and p
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Contact: Kim McDonald
kmcdonald@ucsd.edu
858-534-7572
University of California - San Diego
Source:Eurekalert

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