What Are CHO Cells?
Chinese Hamster Ovary (CHO) cells are a type of cell line derived from the ovary of the Chinese hamster (Cricetulus griseus). Since their development, CHO cells have become one of the most common tools in biotechnology and biomedical research, particularly in producing therapeutic proteins and recombinant biopharmaceuticals. This article explores CHO cells' history, characteristics, applications, and significance in modern science.
Chinese hamsters have been used in research since 1919, initially as substitutes for mice in typing pneumococci and later as vectors in Leishmania research, particularly for the study of kala-azar (visceral leishmaniasis). In 1948, the Chinese hamster was first used for breeding in U.S. research laboratories.
In 1957, Dr. Theodore T. Puck obtained a female Chinese hamster from Dr. George Yerganian's laboratory at the Boston Cancer Research Foundation and derived the original Chinese hamster ovary (CHO) cell line. The rapid growth of CHO cells in suspension culture and their high protein production capabilities made them a preferred cell line in biomanufacturing.
CHO cells gained prominence in the 1980s with the advent of recombinant DNA technology. The first recombinant protein produced from CHO cells, alteplase (Activase), a thrombolytic medication for myocardial infarction, was approved by the U.S. Food and Drug Administration in 1987. Since then, CHO cells have become the most widely used platform for manufacturing recombinant protein therapeutics, with six of the ten best-selling drugs in 2019 being produced using CHO cells.
How it Works
CHO cells, taken from the ovary of a Chinese hamster, are a type of epithelial cell, which means they come from the kind of cells that line the surfaces of organs in the body. This makes them tough and versatile, able to grow in different conditions, which is why they're so useful in making medicines.
These cells are easy to work with in the lab because they can be genetically modified to produce complex proteins, like those needed for drugs. This ability has made CHO cells a go-to choice in the pharmaceutical industry.
Developing a stable CHO cell line to produce antibodies or proteins takes about six months. It starts with creating the gene and inserting it into a vector (like a delivery system). Then, scientists check if the cells are making the protein.
Finally, they select the best-performing cells, make sure they're stable, and store them for future use. The fact that CHO cells are epithelial helps them grow well and produce large amounts of the proteins needed for medicines.
Characteristics of CHO Cells
Several key characteristics make CHO cells particularly useful for scientific and industrial applications:
Adaptability
CHO cells can grow in suspension cultures and adhere to surfaces, making them versatile for different types of bioreactors and culture systems.
Tolerance to genetic manipulation.
Adapts with ease to manufacturing process scales. Human-compatible post-translational modifications.
Genetic Stability
Cell line stability/genetic stability means production process stability.
There are variants of the original CHO cell line, including CHO-K1, CHO-S, CHO-BXD11, CHO-DG44, and CHO-GS.
Each variant behaves differently, meaning that their growth requirements, environmental conditions, and responsiveness are all slightly different.
Because culture conditions are different for each CHO cell line, media choice plays an important role in CHO cell variant performance.
Post-Translational Modifications
CHO cells can perform complex post-translational modifications, such as glycosylation, essential for the activity and stability of many therapeutic proteins.
Small molecules such as lipids, carbohydrates, and polypeptides can be added to the amino acid side chains to make modifications.
The addition alters the phenotypes and biological function of the cells essentially regulating cellular processes and pathways, such as cell cycle, cell metabolism, and autophagy. Common protein PTMs include Methylation, Glycosylation, and Phosphorylation.
High Protein Yield:
CHO cells can produce large quantities of proteins, making them efficient for industrial-scale manufacturing.
Their ability to produce large quantities of protein is determined by production media and feed media conditions.
Applications of CHO Cells
CHO cells are utilized in a wide range of applications within biotechnology and medicine including:
Recombinant Protein Production
CHO cells are the workhorse for producing recombinant proteins, including monoclonal antibodies, hormones, and enzymes. These proteins are used in treatments for cancer, autoimmune diseases, and other medical conditions.
Vaccine Production
CHO cells are employed in developing and producing vaccines, including those for infectious diseases such as influenza and COVID-19.
Gene Expression Studies
Scientists use CHO cells to study gene expression, protein function, and cellular processes, aiding in the understanding of various biological mechanisms.
Drug Screening and Development
CHO cells serve as a platform for screening potential drug candidates, evaluating their effects on cellular functions, and optimizing drug formulations.
Biosafety Testing
CHO cells are used in biosafety and toxicity testing for pharmaceuticals and chemicals, ensuring the safety and efficacy of new products.
Advantages
Scalability
CHO cells can be cultured at large scales, making them suitable for industrial biomanufacturing.
Flexibility
Their ability to grow in various conditions and perform human-like post-translational modifications makes them highly adaptable.
Regulatory Approval
The established history of regulatory approval for CHO-derived products simplifies the approval process for new therapeutics.
Challenges
Cost
The cultivation and maintenance of CHO cells can be expensive, requiring specialized media and growth conditions.
Complexity
Genetic manipulation of CHO cells can be complex and time-consuming, necessitating advanced techniques and expertise. CHO cell lines (mammalian cell lines) are easily contaminated and must be handled using proper aseptic methods and techniques.
Optimization
Producing high yields of functional proteins often requires extensive optimization of culture conditions and genetic constructs.
The Future of CHO Cells
Advancements in biotechnology continue to enhance the utility of CHO cells. Innovations such as CRISPR-Cas9 gene editing, synthetic biology, and improved bioreactor technologies are poised further to increase the efficiency and capability of CHO cells.
Researchers are also exploring ways to reduce production costs and improve the scalability of CHO-based manufacturing processes.
CHO cells have become a staple in the world of biotechnology, driving significant advancements in the production of therapeutic proteins, vaccines, and other biopharmaceuticals. As technology continues to evolve, CHO cells will likely contribute to the development of new and improved therapies for a wide range of diseases.