Innovations

UCSD Photo: Nathan Schoepp

UCSD Photo: Nathan Schoepp

UCSD Developing Anti-Cancer Drugs from Algae

December 10, 2012, by Kim McDonald
AlgaeIndustryMagazine.com

Biologists at UC San Diego have succeeded in genetically engineering algae to produce a complex and expensive human therapeutic drug used to treat cancer.

Their achievement, detailed in a paper in this week’s early online issue of The Proceedings of the National Academy of Sciences, opens the door for making these and other “designer” proteins in larger quantities and much more cheaply than can now be made from mammalian cells.

“Because we can make the exact same drug in algae, we have the opportunity to drive down the price dramatically,” said Stephen Mayfield, a professor of biology at UC San Diego and director of the San Diego Center for Algae Biotechnology or SD-CAB, a consortium of research institutions that is also working to develop new biofuels from algae.

Their method could even be used to make novel complex designer drugs that can’t be produced in any other systems – drugs that could be used to treat cancer or other human diseases in new ways.

“You can’t make these drugs in bacteria, because bacteria are incapable of folding these proteins into these complex, three-dimensional shapes,” said Mayfield. “And you can’t make these proteins in mammalian cells because the toxin would kill them.”

Chlamydomonas reinhardtii, a green alga used widely in biology laboratories, can produce many kinds of “designer proteins.” Courtesy: Laurence A. Moran

Chlamydomonas reinhardtii, a green alga used widely in biology laboratories, can produce many kinds of “designer proteins.” Courtesy: Laurence A. Moran

The advance is the culmination of seven years of work in Mayfield’s laboratory to demonstrate that Chlamydomonas reinhardtii, a green alga used widely in biology laboratories as a genetic model organism can produce a wide range of human therapeutic proteins in greater quantity and more cheaply than bacteria or mammalian cells.

Mayfield and his colleagues achieved their first breakthrough five years ago when they demonstrated they could produce a mammalian serum amyloid protein in algae. The following year, they succeeded in getting algae to produce a human antibody protein. In 2010, they demonstrated that more complex proteins—human therapeutic drugs, such as human vascular endothelial growth factor, or VEGF, used to treat patients suffering from pulmonary emphysema—could be produced in algae.

Then in May of this year, Mayfield’s group working with another team headed by Joseph Vinetz from UC San Diego’s School of Medicine, engineered algae to produce an even more complex protein—a new kind of vaccine that, preliminary experiments suggest, could protect billions of people from malaria, one of the world’s most prevalent and debilitating diseases.

 

“What the development of the malarial vaccine showed us was that algae could produce proteins that were really complex structures, containing lots of disulfide bonds that would still fold into the correct three-dimensional structures,” said Mayfield. “Antibodies were the first sophisticated proteins we made. But the malarial vaccine is complex, with disulfide bonds that are pretty unusual. So once we made that, we were convinced we could make just about anything in algae.”

In their latest development, the scientists genetically engineered algae to produce a complex, three-dimensional protein with two “domains” – one of which contains an antibody, which can home in on and attach to a cancer cell and another domain that contains a toxin that kills the bound cancer cells. Such “fusion proteins” are presently created by pharmaceutical companies in a complex, two-step process by first developing the antibody domain in a Chinese hamster, or CHO, cell. The antibody is purified, then chemically attached to a toxin outside of the cell. Then the final protein is re-purified.

“We have a two-fold advantage over that process,” said Mayfield. “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 researchers – Miller Tran, Christina Van, Dan Barrera and Jack Bui, at the UC San Diego Medical School – confirmed 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 chloroplasts – the part of algal and plant cells where photosynthesis takes place – it 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 domains – one 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 produce a designer protein in algae with multiple functions that doesn’t exist in nature? I think we can,” he added. “Suppose I want to couple a receptor protein with a series of activator proteins so that I could stimulate bone production or the production of neurons. At some point you can start thinking about medicine the same way we think about assembling a computer, combining different modules with specific purposes. We can produce a protein that has one domain that targets the kind of cell you want to impact, and another domain that specifies what you want the cell to do.”

The research project was supported by grants from the National Science Foundation and The Skaggs Family Foundation.

More Like This…

HOME Algae Industry Jobs

Copyright ©2010-2012 AlgaeIndustryMagazine.com. All rights reserved. Permission granted to reprint this article in its entirety. Must include copyright statement and live hyperlinks. Contact editorial@algaeindustrymagazine.com. A.I.M. accepts unsolicited manuscripts for consideration, and takes no responsibility for the validity of claims made in submitted editorial.

From The A.I.M. Archives

— Refresh Page for More Choices
In a global scenario where increasing attention is being directed towards issues of sustainability and limited food supplies, algal sources offer immense scope for the ra...
Technical standards define critical terms and metrics to add wisdom for the algae industry. Agreement among science and business leaders represents possibly the most diff...
“Proterro has reached its Q1 sugar-production pilot milestones,” CEO Kef Kasdin reported at the recent Advanced Biofuels Leadership Conference, in Washington, D.C. “In fo...
Yereth Rosen reports in the Anchorage Daily News that scientists at North Carolina State University’s Plants for Human Health Institute have found extremely high levels o...
A series of articles by Stephen Mayfield and the UCSD Laboratory deserve recognition for their articles on algae-based medicines for malaria and cancer. Mayfield and his ...
Santa Fe Community College has been awarded a $50,000, SEED Infrastructure Grant from the Experimental Program to Stimulate Competitive Research (EPSCoR), for commercial ...
Although the use of whole microalgae in animal diets has long been studied, the 
de-fatted biomass of microalgal species, derived from biofuel production research, has on...
A new, outdoor system at the University of Dayton Research Institute has been producing a high volume of algae since its installation in the summer of 2013, even through ...
Kazuaki Nagata reports from Japan that while the Fukushima nuclear disaster has prompted vigorous discussion about alternative energy in Japan, there is a lack of a paral...
Algae Industry Magazine is pleased to announce a new Algae 101 series by our popular blogger, Mark Edwards, Professor, Arizona State University. The Algae Solutions to Na...
Steven Mufson reports for the Washington Post that Algenol Biofuels estimates hackers have attempted to break into its computers 39 million times in four months this year...
Channelnewsasia.com reports on three young Spaniards who harvest seaweed, a culinary delicacy, as a way for them to stay out of Spain’s troubled financial waters. 35-year...
The EPA has released the Annual Use of Pesticides in the U.S. Report. We now know that American farmers apply roughly a billion pounds of toxic chemicals intentionally in...
Oregon State University researchers are combining diatoms, a type of single-celled photosynthetic algae, with nanoparticles to create a sensor capable of detecting minisc...
Researchers at the Paul Scherer Institute (PSI) in Wädenswil, Switzerland, have succeeded in producing energy-rich gas from microalgae, and in doing so have demonstrated ...
SCHOTT AG, of Mitterteich, Germany, and Algatechnologies Ltd. (Algatech), based at Israel’s Kibbutz Ketura, have signed an R&D agreement to strengthen their partnersh...
Analia Murias 
reports for fis.com that Chilean exports of products made from macroalgae generated a total of $195 million US in the first seven months of 2014, according...
U.S. farmers and biofuels makers are watching for the Environmental Protection Agency’s (EPA’s) final decision on the 2014 Renewable Fuel Standard rules, which will set t...