Danish researchers have created new cell lines that need a less tailored feeding schedule and produce fewer waste products.
The team, from the Technical University of Denmark (DTU), says they’ve designed Chinese Hamster Ovary (CHO) cell lines that produce two essential amino acids and produce no lactate and little ammonia, both key waste metabolites.
“Process optimization right now involves fine-tuning the feeding schedule and composition so the cells remain happy, but if a cell can produce everything on its own, then that’s a leaner process,” explains Hooman Hefzi, PhD, an associate professor in DTU’s Department of Biotechnology and Biomedicine.
According to Hefzi, CHO cells can only produce 7–8 essential amino acids for themselves and require the rest to be provided in the culture media.
To get around this, the team engineered a cell line that also produces threonine and histidine, so they don’t need to be added and controlled as an extra feed during the biopharma production process.
In addition, the team engineered a cell line that doesn’t produce lactate under a wide range of circumstances, including in both producing and nonproducing clones, and which only produces ammonia under certain circumstances.
“As long as the CHO cells are growing, they don’t produce ammonia. They only produce ammonia when they reach a stationary phase (and we think we know why),” he explains.
The team has also tested their lactate strategy in Human Embryonic Kidney (HEK) 293 cells. “We wanted to make sure this wasn’t an idiosyncrasy of CHO,” says Hefzi.
The team now plans to have three Master’s students expand on this work. One student will work on adding the ability to create additional amino acids to the cell line that produces its own amino acids. Another student will also work on testing existing cell lines for antibody production and product quality, while a third student will focus on adding threonine and histidine production to the low-waste-metabolite cell line.
“We’re starting to move our strategies [between cell lines],” says Hefzi. When asked if he was going to do additional testing, add new amino acids, or combine his existing cell lines together, he adds, “We’re going to do all at once, and feel confident we’ll make significant progress in the coming year.”
The team’s lactate work was published in Nature Metabolism.
