This website is no longer being updated. Visit Dartmouth Now for all news published after June 7, 2010.
Dartmouth College Office of Public Affairs Press Release
Dartmouth engineers are one step closer to mass-producing therapeutic proteins desperately needed by today's pharmaceutical industry. Reported in today's early online edition of the Proceedings of the National Academy Of Sciences, the researchers have achieved a major milestone in their efforts to effectively produce human therapeutics using a yeast-based protein expression system.
The research is the result of a collaborative effort between Dartmouth researchers and a bioengineering startup called GlycoFi, Inc. Founded by two Dartmouth engineering professors, GlycoFi is advancing technological solutions for the safe, fast, and cost-effective mass-production of fully-humanized proteins. Protein-based biological drugs must be manufactured by living cells, which are genetically engineered to produce (or express) proteins that mimic the structures synthesized by humans. Current production of these therapeutic proteins is being pushed beyond capacity by exponential growth in the biopharmaceutical industry. GlycoFi's business is to engineer fungal expression systems that produce therapeutic proteins with human-like structures at an industrial scale.
"Production capacity has led to a bottleneck within the biopharmaceutical pipeline," said Charles Hutchinson, co-founder and CEO of GlycoFi, as well as dean emeritus of Dartmouth's Thayer School of Engineering. "The result is that some approved therapeutic protein drugs cannot be produced in adequate amounts, and still others are not making it into commercialization due to the cost and inefficiencies of producing them. It is our hope that this push to producing homogeneous, human-like glycoproteins in yeast will eliminate the production capacity bottleneck, and allow for the production of better and safer drugs."
Fungal-based protein expression systems are safer than conventional mammalian cell culture systems, but have not been effective in replicating complex human glycoprotein structures—until now.
"Demonstrating for the first time the production of 'hybrid' glycosylation structures in yeast brings GlycoFi an important step closer to dramatically improving the capacity and cost of producing therapeutic proteins," said Tillman Gerngross, Dartmouth engineering professor, co-founder and chief scientific officer of GlycoFi, and one of the authors on the paper. "In fact, we have already gone beyond this work and expect to manufacture fully complex human glycoproteins in one of our fungal production systems before the year's end."
Dartmouth/GlycoFi scientists genetically engineered the yeast P. pastoris to perform a series of sequential reactions that mimic the early processing of proteins in humans. After eliminating non-human glycosylation from the yeast, several genes were inserted into the yeast in such a way that the yeast synthesized new human-like glycosylation structures.
"The glycosylation structures we are seeing in our yeast are of a purity and uniformity unprecedented in biopharmaceutical manufacturing," said Stefan Wildt, also a Dartmouth engineering professor, director of strain development at GlycoFi, and another author of the paper. "This will allow GlycoFi to harness the inherent advantages of fungal protein expression systems and thereby address the biopharmaceutical manufacturing industry's capacity issues."
- Catharine Lamm
GlycoFi, Inc. was founded in the spring of 2000 in professor Gerngross's lab at Dartmouth. The company has since transitioned to a new nearby 13,000 sq. ft. laboratory facility. Dartmouth College, located in Hanover, New Hampshire, is a member of the Ivy League and has been in the forefront of American higher education since 1769. Founded in 1867, Dartmouth's Thayer School of Engineering is one of the nation's oldest professional schools of engineering. The School comprises both the Undergraduate Department of Engineering Sciences at Dartmouth and a graduate professional school in engineering. Undergraduate programs emphasize interdisciplinary study in the engineering sciences within the context of a broad-based liberal arts education. At the graduate level, Thayer School offers degrees through the doctorate combining scholarship, research, experimentation, problem-solving, and design.
Dartmouth has television (satellite uplink) and radio (ISDN) studios available for domestic and international live and taped interviews. For more information, call 603-646-3661 or see our Radio, Television capability webpage.