The companies will work together to develop an economically viable biomanufacturing process for a chemical currently manufactured from petrochemical-based raw materials. DuPont CR&D will fund the joint research and development effort. Microbia will also be eligible to receive performance-based payments through the course of the program.

"DuPont is a premier chemical company with a strong track record of technical achievement and a commitment to developing environmentally sustainable processes based on renewable resources," said Richard Bailey, Ph.D., vice president and general manager of Microbia's Precision Engineering business. "Not only does this collaboration provide further validation of our technology, but also it aligns Microbia with a worldwide leader in the increasingly important area of green chemistry."

"Microbia has the capability to accelerate the rate of process development for this important project," said John Pierce, director of DuPont's Biochemical Science & Engineering section of Central Research & Development. "We believe their association analysis technologies will more rapidly identify those genetic elements essential for solving a complex biological challenge and, when combined with DuPont's metabolic engineering capabilities, will accelerate our commercialization timeline."

Microbia's Precision Engineering business applies molecular genetics and proprietary profiling methods to rationally design microbes for the efficient production of commercially valuable compounds in the pharmaceutical and fine chemical industries, as well as the developing industrial biotechnology field. To date, two Microbia-engineered production strains have been introduced into commercial use and a third Microbia-engineered strain is currently undergoing pilot evaluation.

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After passing the viruses three times through increasingly more potent serum, they isolated the survivors and subjected them to another round of PCR that introduced more mutations. After passing this second generation through serum three times, they isolated viruses that could survive AAV antibodies much better than the original strain of AAV. One strain of virus was 96 times more effective than the wild AAV, and two evolved strains survived injection into mice with nearly 1,000 times the level of antibodies required to neutralize the wild virus.

By sequencing the survivor strains, the researchers discovered that the capsid proteins of the survivors differed from those of the original strain by only seven amino acid building blocks, two of which were responsible for most of the altered interaction with antibodies.

"Starting from scratch, just trying to rationally decide which two amino acid changes to make on the virus, there is no way you would have guessed those two," Schaffer said. "Using the same algorithm as nature came up with - evolution - to solve the problem, is the best way to do it."

Since each generation takes about a month, Schaffer predicted that many types of new and improved strains could be created in a few months' time, and certainly in less than a year. He is pursuing experiments now using pooled human blood serum.

"This virus is kind of a gift from nature, a very safe and efficient virus, but nature never evolved it to be a human therapeutic. So, in a sense, we have to re-evolve it for that purpose," he said.

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