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Breakthrough Research

Dartmouth/GlycoFi team makes advance in global effort to increase potency of antibodies

Investigators at the Thayer School of Engineering, Dartmouth Medical School, and the biotechnology firm GlycoFi, Inc., recently reported a breakthrough in using yeast to produce antibodies with human sugar structures.

Antibodies are proteins with sugars attached to them, and they are emerging as a major class of drugs in the treatment of cancer. In the global effort to increase the potency of antibodies, the interdisciplinary work by the Dartmouth/GlycoFi team, published in the February issue of Nature Biotechnology, represents a major advance. The work shows that antibodies with increased cancer-killing ability can be produced by controlling the sugar structures that are attached to them.

Tillman Gerngross and Huijuan Li
Tillman Gerngross, professor of engineering and GlycoFi chiefi scientific officer (left) and Huijuan Li, GlycoFi associate director of analytical development and lead author on the study. (photo by Joseph Mehling '69)

"This work demonstrates for the first time that an antibody with human sugar structures can be produced in a non-mammalian host," says Tillman Gerngross, professor of engineering at the Thayer School and GlycoFi's chief scientific officer.

Huijuan Li, associate director of analytical development at GlycoFi and the lead author on the study, adds, "By controlling the sugar structures on antibodies we have shown that the antibodies' ability to kill cancer cells can be significantly improved and that proteins can be optimized by controlling their sugar structures."

While the current report focuses on antibodies, the approach taken by the GlycoFi team can be applied to any therapeutic glycoprotein. Currently glycoproteins comprise about 70 percent of all approved therapeutic proteins and the therapeutic protein market is expected to grow at over 20 percent annually over the next decade, according to the researchers.

"GlycoFi is the world leader in protein glyco-engineering, and this work is an example of the exciting translational research that has been spun out of Dartmouth," says Gerngross.

GlycoFi was founded in 2000 by Gerngross and Charles Hutchison, professor emeritus of engineering and CEO of GlycoFi. The company continues to maintain its Dartmouth ties, and it is engaged in several ongoing collaborations with Dartmouth faculty. Gerngross says that the environment at Dartmouth is exceptional for bioengineers who seek to take basic life science discoveries and translate them into technologies that benefit patients.

"GlycoFi's achievement has broad potential application to the development of new and improved therapeutics," says Joseph Helble, dean of the Thayer School and professor of engineering. "It is a wonderful example of the benefits of taking a fundamental research discovery from the laboratory and applying it to meet a real-world need, a process that works particularly well not just in engineering, but across all of Dartmouth, because of an outward focus and a collaborative interdisciplinary environment."

GlycoFi is a private, venture-backed biotechnology company whose investors include Polaris Venture Partners, SV Life Sciences, Boston Millennia Partners, Fletcher Spaght Ventures, Eli Lilly & Company, and International Biotechnology Trust.  GlycoFi has also received funding from the National Institute of Standards and Technology, under its Advanced Technology Program, and the National Institutes of Health. GlycoFi leverages its pioneering protein optimization technology to develop, produce, and commercialize Next Generation Biotherapeutics(tm), alone and in partnership with other leading biopharmaceutical companies. 

By SUSAN KNAPP

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Last Updated: 12/17/08