RedHerring.com ~ The Business of Technology

In a triumph of genetic engineering that could lead to more effective drugs, scientists at GlycoFi have developed yeast cells capable of an entire group of chemical reactions found in human cells.

The research published in Friday’s issue of the journal Science is the “crown jewel” of six years of research, according to the Lebanon, New Hampshire-based subsidiary of pharmaceutical giant Merck.

Science

GlycoFi specializes in adding and removing specific carbohydrate attachments to protein molecules. These sugar structures fine-tune the action of over 70 percent of approved therapeutic proteins, often influencing where exactly they go in the body and for how long they hang around.

The new paper describes how GlycoFi scientists knocked out four genes from the yeast genome and added in 14 new ones, of which the majority were entirely synthetic.

The result was yeast cells that can carry out the full repertoire of reactions that add on or remove sugar structures from proteins in humans.

Better Drugs

“Switching to this technology will also provide improvements in product uniformity and overall production economics,” said Tillman Gerngross, chief scientific officer of GlycoFi and professor of Bioengineering at DartmouthCollege.

Since the beginning of the decade, many companies have been trying to find cheaper ways of producing drugs such as therapeutic antibodies, he explained.

These are most commonly made in large vats of mammalian cells, such as Chinese hamster ovary cells.

But the process is expensive so resources have been poured into alternative methods using genetically engineered goats and chickens (see Q&A: GTC’s Geoffrey Cox and Drugs from Chimeric Chickens).

Q&A: GTC’s Geoffrey Cox

Both have successfully produced human antibodies, but, just like the Chinese hamster ovary method, the antibody molecules produced have a mixture of different sugars attached to them.

Potential Potency

In other words, molecules of the same drug can have a very potent action in the body; meanwhile, others are less effective.

Picking and choosing the sugars on the proteins as they are produced in yeast cells allows GlycoFi to iron out these differences.

“The purity of the material generated is unseen using other production methods,” said Mr. Gerngross.

Earlier this year, Red Herring named GlycoFi as one of its top 100 private companies in North America (see Red Herring 100) after it demonstrated it could reconstruct Genentech’s antibody drug, Rituxan, which treats rheumatoid arthritis and a cancer called non-Hodgkin’s lymphoma.

GlycoFi’s version of the drug, which had select sugars attached one by one, proved 100 times more efficacious at killing cancer cells (see Yeast Helps Drugs Work Better).

Merck acquired GlycoFi in May 2006 for approximately $400 million.

Contact the writer:Editorial@RedHerring.com

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GlycoFi Gets Its Crown Jewel