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The big challenge was to equip a bacteria cell with a complex biological pathway that it doesn’t naturally carry. Many people thought it impossible. The big challenge was to equip a bacteria cell with a complex biological pathway that it doesn’t naturally carry. Many people thought it impossible.
Jesse Winter
Jesse Winter

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Glycobia employs what it calls "BUG," bottom-up glycoengineering. Glycobia employs what it calls "BUG," bottom-up glycoengineering.
Jesse Winter
Jesse Winter

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DeLisa’s lab demonstrated a method for engineering human glycosylation reactions in bacteria. DeLisa’s lab demonstrated a method for engineering human glycosylation reactions in bacteria.
Jesse Winter
Jesse Winter

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Glycoproteins are used as medical treatments for heart attacks, asthma, arthritis, and many types of cancers including leukemia.  Glycoproteins are used as medical treatments for heart attacks, asthma, arthritis, and many types of cancers including leukemia.
Jesse Winter
Jesse Winter

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DeLisa filed a patent to protect his novel glycoengineering technology, which Glycobia exclusively licensed. DeLisa filed a patent to protect his novel glycoengineering technology, which Glycobia exclusively licensed.
Jesse Winter
Jesse Winter

Glycoengineering Designer Therapeutics

by Alexandra Chang

It began with a rough sketch on the back of an envelope in 2008. Matthew P. DeLisa, Chemical and Biomolecular Engineering, sat down with then graduate student Adam Fisher. The two jotted down a possible biological pathway for bacteria to make a specific sugar structure (a glycan) and to then transfer and attach the glycan to a protein target in order to make a glycoprotein.

“From that blueprint we could go into the lab and test our ideas,” says DeLisa. The company Glycobia Inc. was born.

Engineering the Technology

The pathway the researchers had drawn onto the envelope is known as "glycosylation." It’s a mechanism important to the function of both healthy and diseased cells. Glycoproteins are also used as medical treatments for heart attacks, asthma, arthritis, and many types of cancers including leukemia. Though most living organisms, including humans, perform glycosylation naturally, most bacteria do not.

At first, although Glycobia existed in name, DeLisa and Fisher, both cofounders of the company, had only their sketch as a proof-of-concept.

“That was the big challenge. Could we equip a bacterial cell with a complex biological pathway that it doesn’t naturally carry?” DeLisa says. “A lot of people thought it impossible. That served as good motivation for us.”

Through basic lab work, DeLisa’s group was able to eventually demonstrate a method for engineering human glycosylation reactions in bacteria. The results were published in Nature Chemical Biology in March 2012. It signified the lab’s major contribution to the field and what DeLisa considers Glycobia’s birth as a startup company.

The results featured in the Nature Chemical Biology article formed the basis of a patent that DeLisa filed to protect his novel “glycoengineering” technology, which Glycobia then exclusively licensed. “It was the perfect storm,” says DeLisa. “With the demonstration of humanized glycosylation in bacteria and the rights to a Cornell technology, Glycobia was in an enviable position, and has since leveraged that position to develop new inventions and new intellectual property.” It didn’t hurt that an MIT Institute Professor and entrepreneur extraordinaire, Dr. Robert Langer, also saw the tremendous promise and agreed to join the board of directors of Glycobia.

Glycobia employs what it calls "BUG," bottom-up glycoengineering, technology to design bacteria that produce novel and enhanced therapeutics to address unmet medical needs. One advantage of using bacterial cells as the chassis for carrying out protein glycosylation is that they have no competing glycosylation reactions; in other words, bacteria are a blank canvas. Current methods of making glycoprotein drugs rely on mammalian cell cultures, such as Chinese hamster ovary (CHO) cells. These cells already have natural glycosylation pathways, which are required to keep the cells alive and thus limit the opportunities for making designer glycans for human needs.

“Because E. coli [Escherichia coli] cells don’t perform any glycosylation reactions naturally, we aren’t restricted to what those systems make,” says DeLisa. “We can get very creative because E. coli glycans are engineered from the bottom up, the cells are indifferent to the reactions we introduce, and there is no interference from endogenous glycosylation reactions. Better yet, we can go back to the envelope and sketch entirely new pathways for making different glycan structures and the proteins to which they are attached, resulting in novel compositions that no other cell-based system can make.”

Glycobia Inc. on the Move

Today, Glycobia is in the process of developing partnerships with large pharmaceutical and biotech companies that are interested in leveraging its technology to improve the quality and performance of drugs.

It’s a major step for a company that sprouts from DeLisa’s graduate school daydreams. At that time, there wasn’t a clear path or understanding of glycosylation mechanisms, says DeLisa. Today’s research environment is dramatically different. Glycosylation is much better understood, and scientific funding agencies are increasingly focusing resources on the study of glycans. For example, the National Institutes of Health (NIH) in 2014 launched the Glycoscience Common Fund to funnel more research dollars toward developing methods and technologies for synthesizing, tracking, and manipulating biomedically relevant glycans and their functions—a fund exactly in DeLisa’s and Glycobia’s wheelhouse.

“It’s very fortunate for the lab and Glycobia,” says DeLisa. “We started down this path more than five years ago at a time when glycoscience was well under the radar. In the last couple of years as we’ve ramped up and become very good at what we’re doing, funding for glycoscience has also started to ramp up.”

Glycobia is already funded heavily by federal grants, with the bulk of that funding—more than $7 million—from the NIH, including a recently funded Phase II Small Business Innovation Research (SBIR) grant to develop glycosylated peptide therapeutics using their proprietary BUG technology platform.

DeLisa says that he founded Glycobia in order to see his scientific discoveries translated to products and to have an impact beyond the walls of the university. “For me, ultimately it was about the opportunity to take those motivational slides that I always put in the beginning of my academic talks, describing what our science could be used for in the future, and to make those slides a reality,” he says.

Launching a company provided access to channels that academia couldn’t offer, DeLisa adds. With Glycobia, the researchers are able to tap into small business funding and, potentially in the future, to take the technology into clinical or preclinical trials for drug development.

Building a Company at Cornell

DeLisa also noted, “To be honest, part of it was dumb curiosity. I heard about starting a company and I wondered what it’s all about.”

As it turns out, founding and building a company is a lot of work. But doing it on Cornell’s campus was a major help to Glycobia. Cornell provides useful resources such as incubator space and services such as DNA sequencing and proteomic analysis, plus mentoring and advice. Though it’s not located in a biotechnology hub like the Bay Area or Cambridge, DeLisa explains that maintaining a close relationship between his lab and the company was an important consideration.

In the process of launching Glycobia, DeLisa says that he often sought advice from other Cornell researchers who have experience starting companies. He hopes that the network of people who have founded startups at Cornell will continue to grow and that the lessons learned by these individuals will be disseminated to further fuel entrepreneurship on campus.

Already, DeLisa sees signs of startup growth at Cornell. “There are more faculty coming to me and asking ‘how did you do that’ than ever before,” he says. “This is just one positive sign that things are changing locally.”

As for Glycobia’s future, DeLisa is open-minded. He’s hopeful that partnerships could lead to an acquisition down the road, but he isn’t shutting the door on the possibility of Glycobia making its own glycoprotein drugs. DeLisa says, “We don’t want to leave anything out of the equation or off the envelope at this point.”