Part of the Solution: How Scientists Create the Cell Lines of the Future

At Sartorius in Ulm, Germany, scientists work on improving cell lines. Their ambition: Get the lines to produce the desired biopharmaceutical protein in large quantities, as fast as possible, and with the right quality. Their work lays the foundation for a faster development of new therapies and more affordable medicine. 

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Sartorius’ products and solutions help simplify and speed up all stages of biopharma production - from cell line development to downstream processing. Cell lines are the production system used to produce biopharmaceutical proteins. These, in turn, are the active ingredients of many live-saving therapies today, including those to treat cancer or rheumatic diseases.  And they are hard to come by: The highly complex molecules cannot be synthesized chemically but must be produced by living organisms – for example cells. While these cells express proteins constantly, the challenge is to get them to produce the desired product in large quantities, as fast as possible, and with the right quality.

This is where the Protein Factory team at Sartorius comes in. Christoph Zehe is Research Fellow and has built up the team from scratch:  "We are part of the Corporate Research team and work on optimizing the productivity of the cells  by editing their genome: How can we prevent unnecessary by-products? How can we speed up or enhance protein production in the cell? How can we identify spots in the cell that are particularly well suited for a high and stable protein production?," asks Christoph.

Three Approaches to Optimizing Cell-Based Protein Factories
 

Less Unwanted Proteins: “In a first approach, we try to get rid of all the unwanted proteins, garbage in other words, that the cell produces. Today, several cost-consuming filtration and purification steps are required to remove those impurities as they could negatively impact the quality of the biopharmaceutical or compromise patient safety,” Christoph explains. Reducing the protein manufactured in the cell to only essentials, would not only simplify the purification process and improve product quality, it would also help free up energy resources in the cell, enabling it to produce the protein of interest more efficiently.  
 

We try to get rid of all the unwanted proteins, garbage in other words, that the cell produces.

Christoph Zehe, Research Fellow

Faster Cell Growth: Addressing the challenge of making biomanufacturing more productive, the team aims to create cells with optimized growth characteristics. Explaining the advantages, Christoph says, "if we can get cells to grow faster, this would lead to higher productivity in manufacturing plants as they would be occupied for shorter time periods. And higher productivity in manufacturing plants means more proteins, means more active ingredients, means more medicine for more people in a shorter time and at lower cost."

Targeted Gene Integration: In a third approach the team tries to identify “hot spots” in the genome that work particularly well for high and stable protein production. “In order to get the cell to produce the desired biopharmaceutical protein, we introduce the gene that encodes this desired protein into the genome. This is called transfection," Christoph explains. "Unfortunately, not all parts of a cell’s genome are equally well suited for producing proteins. Once the “hot spots” have been discovered, it will be possible to introduce genes into these sites in a targeted manner by using gene editing tools. The benefits: cell line development will not only become more reliable and less resource intensive, but also much faster, which, in turn, will – again – speed  up the whole biopharma development and production workflow."
 

The benefits: cell line development will not only become more reliable and less resource intensive, but also much faster, which, in turn, will – again – speed  up the whole biopharma development and production workflow.

Christoph Zehe, Research Fellow

From One-Man-Research to Global Collaboration

The Protein Factory team is not only trying to make cells grow faster but has also grown vigorously itself.  "When I started on Protein Factory work at Sartorius in 2018, it was basically just me and my computer," Christoph remembers. Today, eight people are researching the cell lines of the future. Two more are starting soon. Scientists, Associate Scientists, PhD students, master’s students and interns, all with backgrounds in (cell) biology or biosciences. "We brought the team in from the university, so to speak," Christoph recalls.
 

    Check Out Vacancies for Scientists

The team spends most of its time in the lab. "Our team takes care of the cells, looks after them, cultivates them so they can grow under optimal conditions. And then we modify those cells by genome editing and then observe how the cell changes,” is how Christoph describes what happens in the lab. Other team members, like himself, no longer work directly with the cell cultures, but are involved in technology scouting and monitoring: "I look at what technologies and possible research partnerships are out there, evaluate what's interesting for us and whether we can maybe make a project out of it.” 
 

 
   Learn More About The Cell Culture Technology Center in Ulm, Germany

First Achievements, Big Impact

So far, the Protein factory team has achieved two major steps or enablers, as Christoph calls them: "First, we were able to completely decode the genome of the cell line we are working with. We know the complete sequence of letters, exactly where which genes are located and what the sequences are. And secondly,  we have found alternative genome editing tools. 

    Learn More About Corporate Research Acitivities : Interview-Series with Oscar-Werner Reif, Head of Corporate Research and Chief Technology Officer at Sartorius

A big step for Christoph: "I would describe myself as an application-oriented scientist. I don't want to deal with things only on a theoretical level. I'm interested in how I can apply things, and thus add value to humanity somewhere.” At Sartorius, that's exactly what he found. "The exciting thing for me here is, that I really work with state-of-the-art technology on cutting-edge topics, with which we are at the forefront of cell biology development. And what drives me personally: We are working on the basics here to produce good, affordable, and high-quality drugs and this really makes us a small, but relevant part of the solution in the fight against various diseases." 

Watch the video to learn more about Cell Line Development at Sartorius: