Algae Collaboration Developing Therapeutic Proteins

Excerpted from Bruce V. Bigalow’s recent article in Xconomy.
AlgaeIndustryMagazine.com

Scientists from Sapphire Energy, UCSD, Scripps, and Protelica, 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,” according to UC San Diego biologist Stephen Mayfield. “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.”

Chlamydomonas reinhardtii is used widely as a genetic model organism. The scientists in these studies said that the percentage of human proteins produced in their algal cultures that were properly folded in three dimensions was comparable to the fraction produced by mammalian cell cultures and much better than that produced by bacterial systems. And because algae generate their energy from sunlight and have relatively simple nutrient needs, they said the costs for using them at large scale to commercially produce human proteins should be much lower than for mammalian cell culture, which require expensive fermentation facilities.

With expected improvements in the ability to express proteins in algae, and the continued reduction in algal biomass cost associated with the large scale efforts to use algae for biofuel production, the scientists anticipate at least a ten-fold reduction in the costs over the next few years, which should make algal protein production the least expensive platform available. This reduced cost of goods, coupled with an ability to rapidly scale production in inexpensive bioreactors, suggests that algae may become an economically superior platform for therapeutic protein production in the future.

Mayfield says the findings substantiate 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 every 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 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.

UC San Diego researchers found this alga, seen from the neck of this flask, can also produce human therapeutic proteins.

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.

Flasks of Chlamydomonas reinhardtii are shaken in the UCSD laboratory to enhance growth

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. According to Mayfield 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 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.” —A.I.M.

Bruce V. Bigelow is the editor of Xconomy San Diego. You can e-mail him at bbigelow@xconomy.com or call 858-202-0492.

Photos: Beth Rasala, UCSD