Synthetic biology is edging ever closer to curing disease, scientists told the meeting today.
University of California, Berkeley synthetic biologist Jay Keasling said that he and the company he founded, Amyris Biotechnologies of Emeryville, California, have hit a major milestone in the quest to make affordable malaria drugs.
Keasling and his company have been trying to use synthetic biology, a field that seeks to use engineering principles to improve biological systems, to make a cheaper source of the antimalarial drug artemisinin. The drug costs $3 to $20 per dose – too expensive for most of the millions of patients who need it in poor countries – because it comes from a plant, sweet wormwood, and has been difficult to synthesize.
Keasling and his company have been trying to rewire yeast so that they become factories churning out buckets of the precursor chemical to artemisinin – artemisinic acid. Three years ago, they could only make 100 micrograms per liter of the drug precursor in yeast. Now, Keasling says, they can make 25 grams of the drug per liter – a milestone that should bring the cost of synthetic production down enough so that he and his partners can meet the goal they set last year: to begin selling synthetic biology-derived artemesinin by 2012 for $1 per patient. Amyris and the non-profit drug maker The Institute for OneWorld Health, in San Francisco, signed a deal last March with Paris-based pharmaceutical company sanofi-aventis toward that goal.
“We are now in the scale-up stage and within one to two years, we hope this drug will be out on the shelves in places like Africa at much cheaper cost,” said Keasling. Today, Keasling said one of the synthetic biology tricks used to boost the drug yield involved building biological “scaffolds” into yeast to more efficiently guide enzymes through the drug synthesis pathway. This avoids some of the pitfalls – for instance, the buildup of toxic intermediates – that kept early versions of the system from making large amounts of artemisinic acid. Keasling said more details of the synthetic process he and Amyris used to boost the yield of the drug will be published within a week or two.
He also said that sanofi, Amyris and OneWorldHealth may be able to undercut other suppliers of the drug that engage in practices that are fueling the spread of resistance to artemisinin. “There are rogue manufacturers getting suboptimal drugs, or selling it as monotherapy,” Keasling said. “If we produce it cheaply in tanks, we can control who gets it, and that will prevent resistance in the future.”
Keasling’s artemisinin project is widely seen as at test case for whether synthetic biology will fulfill its promise. But other test cases could be on the way, said Christina Smolke of Stanford University in Palo Alto, California.
Smolke and her colleagues published a paper last October showing how they could combine RNA components into systems that sensed and responded to levels of a drug called theophylline. Now, Smolke says, she and her team have engineered mouse immune cells, called T cells, to grow or stop growing in response to theophylline in mice.
Smolke’s team is now working to modify the same system to work in human T cells. That could aid doctors who are trying to treat cancer by injecting patients with supercharged T cells that destroy tumors. Smolke said if these T cells could be modified so that their growth is tightly controlled by a particular drug, they will be more powerful and safer weapons against cancer.