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Noscapine’s utility as a cough suppressant was discovered in 1930s, and the drug has been widely used since the 1960s. What's more, preclinical trials suggest noscapine has potential as a cancer drug with less toxicity to healthy cells than currently available chemotherapies.
Initially, the bioengineered yeast created by Smolke’s group was able to generate limited amounts of noscapine in three or four days. After tinkering with the recipe — modifying particular genes as well as the medium in which the yeast proliferates — the team was able to speed things up significantly. The result was an 18,000-fold improvement in noscapine output compared with what could be obtained by just inserting the plant and rat genes into yeast.
For those without a background in genetic engineering, the question might arise: So what does an anticancer, bioengineered, yeast-drug factory look like? It's not as space-age as it might seem.
“When doing the genetic engineering part, it looks like designing the sequences on computers,” Smolke said. “In the lab it looks like test tubes, flasks, agar plates—basically combining solutions of yeast with solutions containing modified DNA. When growing the cells for production it looks more sophisticated than a home brew operation. It's a small fermenter, or a vessel with yeast culture in it.”
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The Stanford team hopes eventually to achieve commercial-scale capacity, which will require another hundredfold improvement in efficiency. While similar laboratory bioreactors have been developed, the Stanford research will ideally contribute to a new and improved kind of “living factory.” Antheia Inc., a biotechnology company based in Menlo Park, California, is working to commercialize noscapine production. Smolke co-founded the company and is Antheia’s chief executive officer.
The study was funded in part by the National Institutes of Health and Novartis Institutes for Biomedical Research.
“We are working on a number of things,” Smolke said. “One, further optimizing and scaling the process so that it can be moved into commercial-scale manufacturing. Two, taking the technology and applying it to different plant-derived medicines. And three, leveraging the cell platforms to make novel medicines.”