Unlike the less-evolved bacterial cells, algae are particularly good at folding complex proteins. In fact, even mammalian cells can’t fold certain proteins correctly and require post-production processing to refold them into the correct shape. “This really opens the way to a whole new set of therapeutics,” says George Oyler, a biochemist who’s coordinating the algae research efforts at the University of Nebraska-Lincoln.
Earlier work by Mayfield has shown that algae can also produce human monoclonal antibodies, complex proteins that are produced in mammalian cells and are now being used in some of the most expensive (but effective) cancer treatments. “There are upwards of 80 to 100 of those antibodies in various clinical trials or on the market,” says Oyler. “But the cheapest of those antibodies are on the order of $10,000 or more for a course of therapy. This may open up an alternate platform.”
“There are advantages and disadvantages to algae, just like with other systems,” says Michael Betenbaugh, a biochemical engineer at Johns Hopkins University who specializes in cell protein production. “The systems that are out there already do a pretty good job at making a lot of these proteins. So algae has some stiff competition.” Yeast and bacteria, he notes, are pretty inexpensive, and their culture systems are tried and true–at least for the simpler proteins that don’t require complex folding. But he agrees that the cost advantage over mammalian cells is a substantial one.
Betenbaugh also points out that, unlike mammalian cells, algae produce proteins without attaching sugars to them, a process called glycosylation that’s common to mammalian cells and one that’s often required for the human body to fully utilize and process a molecule. For now, however, Mayfield believes he can avoid this issue: The proteins he’s expressing in algae are ones that are effective without glycosylation, and in the future he thinks it should be possible to do further genetic modifications that allow the plant cells to attach human-like sugars, something researchers have already done in yeast.
Mayfield agrees that it’s not worth messing with a good system, especially when drugs such as insulin are already produced at costs competitive to what algae could do. But with the more complex drugs, algae show great potential. “The most important thing about this paper is that it shows we’re ready for prime time,” he says. He hopes to produce, purify, and test the algae-produced proteins in animal models later this year, and already has researchers in developing nations, such as China and India, interested in the technology and eagerly awaiting his results.