January 29, 2006
Glycosylated Antibodies Produced In Yeast

Many proteins in the body need sugars attached to them (the process is called glycosylation) in very specific patterns to make them work optimally. A biotech company and some university researchers have developed a way to make human monoclonal antibodies in yeast which have sugars attached to them.

Researchers at GlycoFi and Dartmouth College have reported the first production of monoclonal antibodies with human sugar structures in yeast. This research, published online January 22 and in the February issue of the journal Nature Biotechnology, demonstrates that antibodies with human sugar structures (glycosylation) can be produced in glyco-engineered yeast cell lines, and that by controlling the sugar structures of antibodies, their therapeutic potency can be significantly improved. Moreover, this same approach offers the potential to improve other glycosylation-dependent drug properties (such as solubility, half-life, or tissue distribution). Given the mature and well-established nature of yeast-based protein production technology, the reported work also promises to improve the production and scale-up economics of antibody manufacturing.


"Mammalian cell cultures currently used for most therapeutic protein production produce a mixture of glycoforms and typically do not allow for the control of glycosylation," said Tillman Gerngross, chief scientific officer of GlycoFi, and professor of Bioengineering at Dartmouth College. "We have spent the last five years engineering yeast cell lines that perform human glycosylation, which now allows us to glycosylate proteins with unprecedented control and uniformity."

Since yeast can grow so fast and is easier to grow than mammalian cells I'd also expect this approach to eventually lower the production cost for antibodies and other protein products.

The ability to glycosylate antibodies is very important because monoclonal antibodies are used against cancer. The glycosylation makes the monoclonal antibodies more effective.

"By controlling the sugar structures on antibodies we have shown that the antibodies ability to kill cancer cells can be significantly improved and that therapeutic proteins can be optimized by controlling their sugar structures," says Dr. Huijuan Li, associate director of Analytical Development at GlycoFi, and the lead author of the study. She noted that while the current report focuses on antibodies, the approach taken by the GlycoFi team can be applied to any therapeutic glycoprotein. Moreover, in addition to cell killing, this approach can be applied to optimize other protein characteristics such as solubility, therapeutic half-life, tissue distribution and interaction with complement proteins. Currently glycoproteins comprise about 70% of all approved therapeutic proteins and the therapeutic protein market is expected to grow at over 20% annually over the next decade.

Just as the yeast were genetically engineered to use human genes to make useful products for the human body the same is going to be done with other organisms and for even grander purposes. What I'd most like to see is extensive genetic engineering of pigs to create pigs that make organs that are transplantable into humans. That's a more distant prospect. But it is an achievable goal.

Share |      Randall Parker, 2006 January 29 10:10 PM  Biotech Immunology

David Tribe said at January 29, 2006 11:09 PM:

This post is a little misleading as yeast already glycosylates its own secreted proteins, but in a different way to humans (mammals). The point must be that the workers have managed to change glycosylation so that it is now like the human pattern. But a great post none-the-less
GMO Pundit

Engineer-Poet said at January 30, 2006 9:07 AM:

I wonder how this might relate to production of flu-virus surface proteins.

Randall Parker said at January 30, 2006 3:48 PM:

David Tribe,

Sorry, I tend to forget that not everyone knows that all eukaryotes glycosylate their proteins. Yes, the improvement here is to glycosylate using human glycosylation patterns specific to antibodies. Of course yeast already do glycosylation, just not the right sorts of glycosylation for human antibodies.

David Tribe said at January 31, 2006 1:18 PM:

Re Pig Engineering: There are research groups and corporations in Australia that have made substantial progress on humanising the glycosylation of pig cell surface proteins. Search "Saint Vincent's Medical Research + other terms", I think , should lead you there.

annmaria rock said at March 27, 2008 7:27 AM:

I wonder if by chance yeast can cause cancer in the body to grow?

annmaria rock

I feel this could be the case have any studies been done as I feel most of our foods have yeast in them

Anupam said at April 18, 2011 9:14 PM:

Could you please tell me what are the monoclonal antibodies or Fc regions produced using yeast cell lines currently in the market.

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