CHO Cell Line

Chinese hamster ovary (CHO) cells are frequently used to produce protein-based medications for the treatment of cancer, autoimmune disorders, and other conditions. A multinational team of researchers, led by the University of California San Diego, has devised a novel method to improve pharmaceutical production in CHO cells. Researchers have removed a major obstacle to creating cells that can produce more of medications like Herceptin and Rituximab without sacrificing their ability to grow or produce energy by knocking out the gene circuit that produces lactic acid, a metabolite that makes the environment around the cells toxic. Their findings were published in the journal Nature Metabolism. As the "living factories" that generate over half of the most popular protein-based medications on the market today, including treatments for autoimmune disorders, cancer, and other conditions, CHO cells have emerged as crucial instruments in contemporary medicine. However, their low protein output is their biggest fault, even with their success. These medications are more expensive because CHO cells don't always generate enough of the targeted medications to satisfy demand. Researchers have now created a method that should increase the yields of CHO cells used in drug manufacturing. The strategy focuses on lactic acid secretion, a crucial physiological function. Lactic acid is a byproduct of the metabolism of CHO cells during protein synthesis. They generate more lactic acid the more active they are. As we grow cells to produce more drugs, lactic acid builds up and kills the cells, thus reducing the yields of life-saving drugs while driving up manufacturing costs. Nathan Lewis Up until now, attempts to prevent the creation of lactic acid have primarily involved blocking lactate dehydrogenase, the enzyme that is in charge of this process. However, as lactate dehydrogenase is necessary for cell survival, these attempts have failed. If you try to remove it or block it, the cells die, This has been demonstrated in multiple studies. Nathan Lewis Lewis and associates adopted a different strategy in the latest work, which was co-led by Hooman Hefzi, a Ph.D. graduate of UC San Diego's bioengineering program who is currently a professor at the Technical University of Denmark. They identified a network of genes that cooperate to regulate the generation of lactic acid, five of which are found in CHO cells and six in human cells, rather than concentrating on lactate dehydrogenase alone. The overproduction of lactate by the cells was thought to be caused by this gene circuit. The CHO cells ceased to produce lactic acid when the researchers disrupted this gene circuit. Additionally, the cells grew better and produced noticeably more protein-based medications, including Rituximab and Herceptin, which are used to treat lymphoma and breast cancer, respectively, than similarly treated controls. Other therapeutic proteins, such as erythropoietin, which promotes the synthesis of red blood cells, and Enbrel, a medication used to treat psoriasis and rheumatoid arthritis, were also successfully produced by the modified CHO cells. The Warburg effect is being challenged. This study also clarifies the Warburg effect, a crucial biological mechanism. The Warburg effect, a metabolic change that leads cells to overproduce lactic acid, was first noticed in cancer cells by German scientist Otto Warburg a century ago. It has long been believed that this activity is essential for the creation of energy and cell division. However, the recent study casts doubt on that idea. Researchers discovered that when the Warburg effect was removed from CHO cells, the cells' growth rates and energy output remained normal. According to this, the Warburg effect might not be as important as originally thought. The newly modified "Warburg-null" CHO cells, according to the researchers, are also compatible with industrial cell line production procedures. This could revolutionize biomanufacturing since these cells could be readily incorporated into actual medication manufacture. Also Read: Newly Developed Tool for Synthetic Biology Which Supports DNA Nanorobots That Can Alter Artificial Cells The team is still investigating the effects of these modifications on the entire drug manufacturing process, and they have found other adjustments that increase the productivity of the CHO cells. Our work has the potential to make drug production far more efficient, which could significantly lower manufacturing costs, By improving the productivity of these cells, we’re taking an important step toward making life-saving therapies, like cancer treatments and gene therapies, more affordable and accessible to patients worldwide. Nathan Lewis Source: UC San Diego Today Journal Reference: Hefzi, Hooman, et al. "Multiplex Genome Editing Eliminates Lactate Production Without Impacting Growth Rate in Mammalian Cells." Nature Metabolism, 2025, pp. 1-16, DOI: https://doi.org/10.1038/s42255-024-01193-7.

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A long-standing challenge with CHO cell line is solved by a new understanding of lactic acid metabolism in cells

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