Producing the World's Most Difficult Proteins
From off-the-shelf proteins to custom protein products, Bio-Techne’s protein leadership team provides high-grade project-specific solutions.
Anthony Person is a protein expert who has walked both the worlds of academia and the biopharmaceutical industry. Person earned his PhD from the University of Arizona, where he discovered the role of the TGF beta superfamily and WNT glycoproteins in the morphogenesis of mitral and tricuspid valves in chicken and mouse models. He continued his research as a postdoctoral researcher at the University of Minnesota, where he discovered how mutations in WNT proteins cause outflow track effects in the heart. He then transitioned to a position in the protein bioassay unit at R&D Systems, a Bio-Techne brand, for two years before taking a job at Cellscript, a Madison Wisconsin company, where he focused on developing mRNA-based cellular transformation technologies. In 2013, Person returned to the Bio-Techne bioassay unit. Committing himself to the production of proteins, Person became the associate director of molecular and cell culture at Bio-Techne, and in 2018, he became the senior director of protein development. Person’s protein development group specializes in making the world’s most difficult proteins for research and therapeutics.
What we love about protein production at Bio-Techne is that we enable all types of science: academic, biotech, clinical research organization (CRO), and pharma. This last year has been exciting for us because we really worked hard making coronavirus proteins that enable antibody therapies; they also make great tools for vaccine development and even diagnostic development. In particular, we made a lot of spike proteins. That was an exciting bit of science for us to execute. We have more than 140 different SARS proteins on the market now, all of which were released last year. So, it has been a fun time to be a protein scientist because we are enabling therapies that are positively impacting patients.
We have more than 5,000 different off-the-shelf research grade proteins and good manufacturing (GMP) proteins for clinical applications. We also have robust custom services where we take custom projects from a variety of pharmaceutical companies, biotech, and academia. We can make some of the most challenging proteins on earth, and that's what we pride ourselves in: making proteins that others have failed to make.
We brought our first recombinant protein, interleukin 2, to market in 1988. The director of our molecular biology department has been making proteins for 33 years. We have some of the best protein biochemists on earth in our protein purification department; they have seen it all and have good strategies for overcoming challenges. We also work with state-of-the-art infrastructure for doing side by side clone screening that allows us to pick clones and plasmids for transient production that give us high levels of expression and secretion of our proteins. So, it comes down to our experience. We have been making proteins longer than most other companies, and that rich history allows us to succeed where others have failed.
What is the process for making custom protein?
Generally, a customer will post an inquiry through our custom services portal on our website. Then our customer service representatives initiate a conversation to understand the customer's needs. From there, the project moves to our technical team, where we put together a statement of work with gated timelines. From there, we test if we can express the gene of interest in our various host systems, and send the customer a sample of the protein at a small scale to test in their applications. If the customer approves, then we scale-up and provide mass quantities of the protein for their work. When we launch custom projects, we work with confidential information. We do not share this with anyone besides the customer; we take that very seriously.
The first step is to optimize production at small scale for high yields. We optimize our expression levels and the amount of protein secreted from our cells in a mammalian system. Or if the protein is in E.Coli, we optimize expression in our refolding process at small scale. It all depends on the needs of the customer. We have capacity to scale production of mammalian and E. coli-derived products well into the gram levels if needed for the customers downstream applications.
The same experts that make our off-the-shelf products are involved in custom workflows. That is the beauty of it; we get on the computer or the phone and interact directly with our custom clients and our technical leaders. Our customers get the best interaction on these custom jobs. We handle it all internally, bringing our molecular people, purification people, cell culture people, and whoever we need to into the meetings to make sure all relevant information is conveyed.
Can you talk about Bio-Techne’s GMP services?
Our customers use our GMP proteins as ancillary materials for clinical applications, and they deserve a consistent supply of high quality proteins with minimal lot-to-lot variability. We provide complete documentation of how our GMP proteins are produced and how they perform in quality control testing. Whenever possible, our GMP proteins are produced under strict animal-free conditions including all materials, equipment, dedicated laboratories, and documentation. Of course, our Quality Team ensures compliance with all relevant guidelines from governing authorities.
There are real time pressures for getting new products out. For example, we just got the new Delta variant of the SARS-CoV-2 spike protein up on our website. We have to move as fast as we possibly can to make those products available because pharmaceutical companies and biotech researchers need these proteins now. We had to compress our time to market. To do so, we have been using our transient platform where we make the plasmid, transfect it into HEK 293 cells, make the protein as quickly as we can, purify it and get it on our website in the shortest time frame possible.
Protein stability and formulation are important. Quite a few of our competitors will get proteins to the market fast, but if we look at them from an analytical perspective, they are not very stable proteins. They are formulated in buffers that are not amenable to long term stability, freeze thaw stability, or four-degree stability. That is something that a lot of people do not put a lot of thought into. Formulation and stability testing are critical for high quality products. We pride ourselves on having world class bioassay capabilities to make sure our proteins are the same lot-to-lot. They are stable over time; they will not fall out of solution if researchers freeze and thaw them or store them at four degrees Celsius for extended periods.
We always have to be on the cutting edge of innovation. We bring in state of the art development equipment that allows us to make plasmids faster, and we use cell culture devices that allow us to do side by side reactions in a controlled automated fashion. We automate purification to make the best proteins and use structural biology to make designer cytokines. Some areas we plan to focus on include structural biology to design new cytokines, automation to remove human error from production, and scaling.
What are the advantages of protein production with Bio-Techne?
We make the highest quality proteins in the business. We go out of our way to show lot-to-lot consistency. We offer robust stability testing. We have a large analytical core that consistently looks at our proteins to make sure that they are correct and that there aren't any contaminants. We are a premium vendor of proteins. If you want the best proteins in the world, come to us.
Ancillary Materials that Streamline Translation to Clinical Manufacturing Mini Poster
