Two Nebraska researchers have launched a startup company aimed at bringing to market an innovative method for delivering therapeutics, gene editing tools, plasmids and more to targeted locations in the human body.
Minovacca, recently incorporated by Janos Zempleni and Jiantao Guo, will commercialize the use of universal milk exosomes - natural nanoparticles contained in milk - to transport cargo to human cells. Drawing on bioorthogonal chemistry techniques, the researchers achieve target-specific delivery by chemically and genetically engineering the exosomes. NUtech Ventures, the university's nonprofit commercialization affiliate, has filed a patent for the technology.
The technology's flexibility means it could be used to treat common and rare diseases alike - a potential boon to rare disease communities, which struggle to secure research funding because of the relatively small patient base.
Because our technology is so versatile, we are not limited to one particular rare disease. We can actually use this same technology to tailor to a large number of rare diseases. Rare disease groups are so thankful that there is maybe a light at the end of the tunnel."
Janos Zempleni, Willa Cather Professor of nutrition and health sciences
The company's launch is the culmination of years of research at the University of Nebraska–Lincoln, first proving the viability and safety of milk exosomes as a transport mechanism, then incorporating the genetic engineering and bioorthogonal chemistry techniques enabling targeted delivery. Zempleni credits funding from the U.S. Department of Agriculture's National Institute of Food and Agriculture (A1511 Nanotechnology for Agricultural and Food Systems program), the National Institutes of Health's Targeted Genome Editor Delivery Challenge and the Syngap Research Fund for propelling the research to this point.
Minovacca is working to license the technology through NUtech Ventures, and Zempleni hired a CEO with expertise in the pharmaceutical industry. Minovacca has acquired office space at Nebraska Innovation Campus and expects to expand its facilities after pinpointing investors.
The company will open the door to job opportunities for Husker students in the pharmaceutical space. Minovacca plans to hire Nebraska students whose work will drive the company toward a major milestone: submitting an Investigational New Drug Application to the U.S. Food and Drug Administration, which is a formal request to administer an investigational drug or bioproduct to humans.
Minovacca's programmable milk exosomes represent a major advance over existing approaches because they enable targeted delivery of therapeutics with an unprecedented level of potency and specificity. Zempleni first demonstrated the safety and scalability of the milk exosomes and developed genetics protocols for making programmable milk exosomes. He then brought Guo, professor of chemistry, on board to devise a strategy for directing the exosomes to particular cellsdepending on the disease at hand.
Their approach is to attach three peptides - short amino acid chains - to the membrane of each exosome. One is a homing peptide, which directs the exosome to bind to a specific site in the body. Another is a "do not eat me" peptide, which sends biochemical signals that allow the exosome to thwart macrophage destruction. The last is a retrofusion peptide, which fortifies the exosome's survivability once it enters the target cells.
Zempleni and Guo developed a novel approach for anchoring the peptides to the exosome membrane. The traditional approach is to use lipid anchors, but these detach when attracted to other lipophilic compounds in the body. To prevent this, the team created docking sites in a membrane protein called CD81, which is firmly anchored to the exosome.
Guo used bioorthogonal chemistry approaches to create stable, covalent links between the docking sites and the peptides. The attachment scheme provides stability and uniformity to the exosome structure, boosting the commercial viability of milk exosome-based therapeutics.
"Ensuring this homogeneous structure will allow the FDA to see that the exosomes can be produced consistently from batch to batch," Guo said.
The strategy overcomes one of the major flaws of current drug delivery approaches. Oftentimes, the therapeutic reaches cells beyond the targeted locations, causing adverse effects. For example, patients receiving chemotherapy often deal with hair loss, gastrointestinal upset and compromised immune function.
"Chemotherapy treatments kill not only cancer cells; they kill any cell that is proliferating fast," Zempleni said. "And that's something that we want to minimize with our technology."
Zempleni said forming Minovacca has been a steep learning curve and an opportunity to expand his thinking beyond day-to-day research. To name the company, he drew on his knowledge of Greek and Roman mythology, which features the Minotaur, a human-bull hybrid. The name aims to reflect the company's use of milk to help humans - but since bulls don't produce milk, Zempleni changed "taur" to "vacca," the Latin word for cow.
No matter which role he is in on a given day - creative, scholar or now entrepreneur - Zempleni's goal is always the same.
"It might sound cheesy, but if I had a choice between making $10 million in the company or saving 10 million lives, I would go for saving the lives," he said. "I'm not into this for the money. It's about helping people."
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