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Scientists from Sapphire Energy, UCSD, Scripps, and Protelica Show Genetically Modified Algae Can Make Important Drugs

Xconomy San Diego — 

Scientists in San Diego and Hayward, CA, have demonstrated the feasibility of using algae to produce commercial levels of human therapeutic proteins that are currently being used to treat emphysema and other diseases, or are in clinical trials for use to boost the immune system.

“The bottom line from the study is that the algae expression platform is ready for prime time,” UC San Diego biologist Stephen Mayfield writes in an e-mail to me over the weekend. “We can express a very high percentage of recombinant genes (at least as good as the best system out there) and they are soluble and bioactive.”

Mayfield says the findings substantiate something he told Denise in December—that algae could dramatically cut the costs of making complex proteins, including interferons, antibodies, and growth factors that already are being used to treat cancer and other diseases. Such complex drugs are currently produced from mammalian or bacterial cells. Algae, though, is much less expensive to work with, and algae cells grow much more quickly—doubling in number ever 12 hours.

“Obviously the scalability and cost of algae make the system attractive, but if you can’t make a high percentage of proteins then costs don’t really matter that much,” says Mayfield, who led the study. The research, published online this week in Plant Biotechnology Journal, included scientists from The Scripps Research Institute (TSRI), San Diego algae biofuels company Sapphire Energy, and Protelica, (previously known as ProtElix) a Hayward, CA-based startup that specializes in protein engineering. Mayfield joined UCSD in November from TSRI, where he had worked since 1987.

Mayfield said a few months ago that a factory that uses algae to produce biotechnology drugs would be significantly cheaper to build than a traditional facility, and drug production costs would be about 75 percent lower. He contends that pharmaceutical companies could use such savings to dramatically cut the costs of some drugs that now cost consumers tens of thousands of dollars a year.

The process the scientists used to genetically modify a garden-variety green algae known as Chlamydomonas reinhardtii, was not universally successful. Of seven proteins that the group selected, Mayfield says the algae expressed four at levels sufficient for commercial production. “No one is really sure why some protein express and other don’t, that’s just the way it goes in all expression systems, ours included,” Mayfield says.

Mayfield, an expert in the genetics of algae, is a co-founder of the San Diego Center for Algae Biotechnology and a scientific co-founder of Sapphire, which is developing algae-based biofuels with funding from Bill Gates’ Cascade Investments, Arch Venture Partners, and others. He tells me that the researchers filed patents on the technology and Sapphire holds the license.

Two years ago, Sapphire acquired Rincon Pharmaceuticals, a biotech that Mayfield co-founded to commercialize his research—which included recombinant DNA techniques for inserting human genes into algae, prompting the cells to make human proteins. Mayfield tells me he hopes to launch an algae protein expression company this year to commercialize the system, “and will be out pitching this to venture groups in the next few months.”

Bruce V. Bigelow is the editor of Xconomy San Diego. You can e-mail him at bbigelow@xconomy.com or call (619) 669-8788 Follow @bvbigelow

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  • Jerry Jeff

    I guess I can understand the advantage over mammalian cells (faster doubling time and maybe cheaper cultivation), but what’s the advantage of algal protein expression over bacterial or yeast systems? It can’t be doubling time, so is it cost of cultivation? Photons are cheaper than sugar, but photobioreactors aren’t cheap. I know this isn’t a technical space, but any clarification would be welcome as to why this is noteworthy.

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  • Steve Mayfield

    Response to Jerry Jeff: The big advantage of algae over bacteria or yeast is the ability of algae (they are eukaryotic) to make complex mammalian proteins. Bacteria and yeast are good at producing small simple proteins, not so good at multi-domain proteins. Algae can handle making these complex proteins, and in fact we produced a fully assembled human monoclonal antibody in algae (Tran et al. 2009 Synthesis and assembly of a full length human monoclonal antibody in algal chloroplast. Biotechnology and Bioengineering 104:663-73) just last year. The second advantage is scaling costs, photobioreactors cost something, but compared to stainless steal fermentors they are a fraction of the cost for large scale (100s of Kg) production, and when you want to go 1000s of Kg, fermentation simply becomes too expensive.
    So will algae replace CHO, bacteria or yeast for production of all therapeutic proteins? No, probably not, but it adds a nice new technology to the arsenal, and one that may get the price of protein therapeutics down from what is presently a rather expensive proposition.

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