When they need a lot of protein from a reliable source, researchers within the University and from outside companies turn to the BRC. We provide the expertise and equipment to help clients develop processes that work at production scale.Along the way, our full-time employees also train undergraduate students in an industry-like setting and help them clarify their professional goals.
Bulking up protein production
Almost every cell in the body contains lipid droplets, the cellular compartments that store fat. For a long time, scientists ignored the tiny particles, thinking they were inert. Now, new research suggests those droplets may play a role in aging and the progression of diseases like obesity, metabolic syndrome, and cancer. Doug Mashek, a nutritional biochemist at the University of Minnesota, studies the breakdown of those lipids and the molecular pathways they trigger, which may slow the aging process and prevent disease.
In fact, Mashek and his collaborators at Mayo found that flies genetically engineered to produce more of an enzyme that breaks down fat live 50 % longer.
Mashek relies on a particular protein that helps regulate lipid storage and metabolism. He needs a lot of it, as Mashek explains, to “help tease apart our mechanism.” The BRC helps make this research possible by producing the protein in bulk, a cost-effective solution that allows research to move forward.
What motivates Mashek, he says, is both “the detective part of figuring out mechanisms and the possibility of improving the overall health of mankind.”
Fermenting anticancer drugs: designed to bind
Daniel Vallera, of the University of Minnesota’s Masonic Cancer Center, is looking for a better way to treat cancer. Chemotherapy, while effective, does not work for everyone and can have devastating side effects. Vallera, a Professor of Therapeutic Radiology and Radiation Oncology, is developing new drugs that can either work in conjunction with chemotherapy or replace it.
Vallera’s anticancer drugs combine two active elements with one to target the cancer cell, and the other to attack it. One drug combines a protein that binds to the cancer cells with diphtheria toxin to kill them. Another drug attacking the most common form of adult leukemia (myelogenous leukemia), uses antibody fragments that connect an immune cell to a cancer cell, and adds a signaling molecule that stimulates the proliferation of immune cells. “It’s better to have a whole army than to have one soldier,” Vallera said.
At the BRC, development of the anticancer drugs starts with bacterial fermentation, where bacteria produce these specialized proteins. The drugs are purified at Molecular and Cellular Therapeutics (MCT), an FDA compliant facility right across the street from the BRC on the St. Paul campus. “We’ve come up with a grassroots program where we begin by inventing a drug approach. We genetically engineer bacteria to produce it, then we quality control it,” Vallera said. “We work with the FDA, get it approved, and have the clinical trial here at the university as well.”
For some, new treatment options could be life-changing. Cynthia Cattell, a physics professor at the University of Minnesota, was diagnosed with B-cell lymphoma. She tried chemotherapy, radiation, bone marrow transplants, and immunotherapy to no avail. After taking a drug the Vallera lab developed, she went into remission for two years. That drug is now in phase II clinical trials.
Scaling up to clinical trials
GeneSegues, a Minnesota company that develops targeted cancer treatments, also relies on the BRC to supply their protein. These protein nanocapsules protect drug molecules from degrading before they get to their target site. RNA interference (RNAi) molecules within the capsules work like dimmer switches for genes important in cancer cells.
The company’s first drug, GS-10, treated head and neck cancer successfully in animal models. Now in the preclinical phase, GeneSegues plans to file an investigational drug application with the FDA. The BRC helped them scale up production of their targeting protein, tenascin, a crucial step on the path toward clinical trials.
As CEO Laura Brod described the problem, “there is a very well known, high unmet need in pharma for targeted delivery that works. We believe that our delivery technology could unlock the promise of billions of dollars of pharmaceutical development.”
Brod has a long-standing connection to the University of Minnesota. She and her eight older siblings have a combined 54 years at the U, and Brod serves on the University of Minnesota’s Board of Regents. She has high hopes for the role of the BRC in the future of biotech in Minnesota. “Having a local resource like the BRC is critical for biotech here in Minnesota. Biotech in Minnesota is on the front end of booming.”
From bench to pilot to production
Farmers in Asia have been raising silkworms for over 6,000 years to produce beautiful fabrics, but a Minnesota startup, Silk Technologies, hopes to use the proteins derived from silkworm cocoons in new medical applications.
Silk Technologies has developed a refining process that dissolves silk protein completely in water. They are developing an eye drop containing the protein as a treatment for dry eye disease. Their silk derived protein works as an anti-inflammatory agent that also helps the cornea retain moisture. They plan to begin a clinical trial in 2019.
It is a big leap for a company to go from bench scale to production scale. The BRC was uniquely positioned to offer knowledge and equipment for the crucial step in between—pilot scale. The BRC also consulted as the company built its facility and helped Silk Technologies scale up the washing, filtering, and purification of their silkworm cocoons. “Where most people fail,” says CEO Brian Lawrence, “is getting your process to a point where it is scalable. I would collaborate with the BRC again in a heartbeat.”