Dartmouth Engineer - The Magazine of Thayer School of EngineeringDartmouth Engineer - The Magazine of Thayer School of Engineering

Innovations: GlycoFi Bought by Merck

PARTNERS: Profs Tillman Gerngross, left, and Charles Hutchinson used yeast to raise a thriving company. Photograph by Joseph Mehling ’69.
PARTNERS: Profs Tillman Gerngross, left, and Charles Hutchinson used yeast to raise a thriving company. Photograph by Joseph Mehling ’69.

When professors Tillman Gerngross and Charles Hutchinson co-founded GlycoFi Inc. in 2000 they knew they were onto something with huge potential. Six years later they found out what their proprietary technology for turning yeast cells into therapeutic protein factories was worth: $400 million.

That’s the price drug manufacturer Merck paid to acquire GlycoFi in June. Citing statistics from the National Venture Capital Association, The Boston Globe reported that “the deal was the third-highest price paid for a private biotechnology firm, and the largest on record to be done in cash.”

The size of the deal reflects the importance of GlycoFi’s scientific breakthroughs. In the September 8, 2006 issue of the journal Science, researchers from GlycoFi, Thayer School, and Dartmouth Medical School announced that they had achieved the complete humanization of the glycosylation pathway in the yeast Pichia pastoris.

“We’ve successfully completed one of the most complex cellular engineering endeavors undertaken to date,” said Gerngross, chief scientific officer of GlycoFi, which is based in Lebanon, N.H.

“Humanizing glycosylation in yeast was a tour de force of genetic engineering, requiring the knockout of four yeast genes and the introduction of over 14 heterologous genes,” said Stephen Hamilton, the lead author of the Science paper and a senior scientist at GlycoFi.

More than half of all drugs currently in development worldwide depend on the genetic engineering of living cells to produce specific recombinant proteins. Most of these proteins require the attachment of sugar structures, a process known as glycosylation, to attain full biological function. Conventionally, these proteins are produced in mammalian cells. But mammalian cells are prone to contamination by pathogens and are expensive to culture, and glycosylation of mammalian cells is hard to control.

GlycoFi engineered strains of yeast to perform controlled, reliable, specific glycosylation, producing proteins with improved therapeutic capabilities. The technology optimizes drug performance while improving manufacturing efficiency.

Glycoengineering Pichia pastoris to produce functional erythropoietin, a protein widely used in treating anemia, was the latest demonstration of GlycoFi’s protein engineering prowess. Earlier this year GlycoFi and Dartmouth researchers published a paper in Nature Biotechnology detailing the role of glycosylation structures on antibodies.

“By engineering yeast to perform the final and most complex step of human glycosylation, we will be able to conduct far more extensive structure-function investigations on a much wider range of therapeutic protein targets,” said Gerngross.

No wonder Merck bought the company. “Our acquisition of GlycoFi’s scientific expertise, patent estate, and robust technology platform is a significant step toward enabling Merck to discover, optimize, and develop novel biologic drugs to serve the needs of patients worldwide,” said Peter S. Kim, president of Merck Research Laboratories.

For Gerngross, who will continue to guide Glycofi’s scientific work, and Hutchinson, who relinquished his CEO duties, the sale to Merck represents the best of both worlds: a profitable end and a promising beginning.

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Categories: The Great Hall, Innovations

Tags: engineering in medicine, entrepreneurship, faculty, innovation

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