Chinese Hamster Ovary (CHO) cells are a cell line derived from the reproductive tissue of the Chinese hamster, Cricetulus griseus. These cells serve as microscopic factories for the production of complex, protein-based drugs known as biologics. The pharmaceutical industry relies on CHO cells to synthesize a vast majority of therapeutic proteins, including treatments for severe and chronic diseases. This cellular system enables the mass production of specialized medicines.
Defining Characteristics of CHO Cells
The widespread use of CHO cells in industrial manufacturing stems from several key traits. CHO cells are an immortalized cell line, meaning they can be grown and propagated indefinitely in a laboratory setting. This allows pharmaceutical companies to maintain a consistent, stable source of the cellular machinery necessary for continuous, large-scale production.
A feature that sets CHO cells apart from simpler hosts like bacteria or yeast is their ability to correctly process complex proteins through post-translational modifications (PTMs). The protein often requires further modification to become fully functional. The most important modification is glycosylation, which involves adding complex sugar molecules, or glycans, to the protein structure.
This human-like glycosylation is accomplished because CHO cells are mammalian cells, and their internal machinery closely mimics the processing pathways found in human cells. Therapeutic proteins produced in bacterial hosts, such as E. coli, often lack these complex sugar structures, which can render the resulting drug ineffective or cause an unwanted immune reaction in patients. By performing these modifications, CHO cells ensure that the resulting drug is stable, has the correct half-life, and functions properly once administered to a patient.
The adaptability of CHO cells to industrial conditions contributes to their status as the industry standard. They can be cultured in suspension, meaning they float freely within a liquid medium rather than needing to anchor to a surface. This suspension culture is essential for scaling up production, allowing billions of cells to be grown in massive bioreactors. CHO cells thrive in chemically defined, serum-free media, eliminating the need for animal-derived components and improving the safety and consistency of the final therapeutic product.
The Workhorse of Biologics Production
CHO cells are the dominant manufacturing system for protein-based medicines in the biopharmaceutical industry. They produce 60 to 70 percent of all recombinant biologics currently on the market. This includes virtually all therapeutic monoclonal antibodies (mAbs), a class of drugs that accounts for approximately 80 percent of U.S.-licensed antibody products.
These monoclonal antibodies are specialized proteins designed to target specific molecules in the body, which has revolutionized the treatment of complex conditions. For example, mAbs are used extensively in oncology to target cancer cells and in the treatment of autoimmune diseases like rheumatoid arthritis and Crohn’s disease by neutralizing specific inflammatory agents. The cells also produce recombinant proteins such as various hormones, enzymes, and blood coagulation factors.
The scale of this production is large, with commercial biomanufacturing processes utilizing large-scale bioreactors that can hold hundreds or even thousands of liters of cell culture. Through optimized processes, CHO cells in fed-batch cultures can achieve high product titers, often yielding between 1 and 10 grams of therapeutic protein per liter of cell culture. This high productivity is what makes the manufacture of these drugs economically feasible for a global patient population.
The long history of successful use has established a regulatory precedent for CHO-derived products. Regulatory bodies, such as the Food and Drug Administration (FDA), have decades of experience assessing the safety and quality of proteins produced in this specific cell line. This established regulatory pathway provides confidence for manufacturers, aiding in the development of new therapeutic agents.
Engineering CHO Cells for Better Results
Researchers are continuously applying advanced molecular biology techniques to improve the performance of CHO cells beyond their natural capabilities. Genetic engineering strategies are employed to enhance the cell line’s productivity and the quality of the therapeutic protein it produces. The goal is to maximize the amount of drug created while ensuring that the final product meets stringent quality standards.
Gene editing tools, such as the CRISPR/Cas9 system, allow scientists to make precise, targeted changes to the CHO cell genome. These modifications can be used to insert multiple copies of the gene coding for the therapeutic protein, thereby increasing the overall protein yield. Other modifications focus on improving cellular resilience, making the cells more tolerant to the physical and chemical stresses inherent in large-scale bioreactor environments.
Furthermore, genetic manipulation is frequently used to fine-tune the post-translational modification process, particularly glycosylation. By engineering the metabolic pathways within the cell, scientists can optimize the profile of the attached sugar molecules to improve the drug’s efficacy, half-life, or binding affinity to its target. These efforts often involve optimizing the cell’s internal machinery to reduce unwanted byproducts and ensure a more homogenous final product.
The industry also uses specialized selection systems to isolate the most productive cell clones. For instance, systems based on dihydrofolate reductase (DHFR) or glutamine synthetase (GS) allow researchers to select for cells that have successfully integrated and amplified the gene of interest. This rigorous selection process ensures that only the highest-performing cells are chosen for the final manufacturing cell line, further enhancing the efficiency of biopharmaceutical production.