Controlling hamster cells, the workhorse of the biopharmaceutical industry

Hamster Cells are key for the biopharmaceutical industry as they can be grown in a bioreactor to produce biopharmaceutical drugs. Those cells can be genetically modified to enhance their productive characteristics thus potentially lowering the cost of manufacturing advanced drugs.

Chinese hamsters can be credited with saving thousands of lives per year because of the ability of their contribution to producing therapeutic proteins that can be used in the treatment of cancer, anemia, and multiple sclerosis amongst other conditions. Most people will never have heard of Chinese Hamster Ovary (CHO) cells but these are one of the main cell factories used by the biopharmaceutical industry to produce these important protein drugs.

Over the last 40 years, Chinese Hamster Ovary cells have been successfully used to produce some ground-breaking therapies such as anti-blood clotting factors (tissue plasminogen activator or tPA) antibodies for cancer therapy. Research on the field has thrived to obtain fast growing and highly productive cells, but there is still little understanding of the basic mechanisms that make cells be that way, leading to a bottleneck in terms of further improving them.

Therapeutic proteins are very complex molecules that cannot be man-made. That’s why, we use cells to make them for us, using them as factories. Inside the cells, genes contain the information as a sort of coded instructions manual, that guides every single process happening in a cell. This code can be translated into proteins, which are responsible for most of the cellular functions, including energy production, cell division, and cell death.

Therefore, gaining the ability to switch ON and OFF genes in these cells implies being able to control when and how particular processes are happening in it, and would represent a major step forward towards being able to create high-performing cell-factories, ultimately bringing down the therapies’ costs and making them more accessible to patients all around the world.

My research as part of the Mammalian Cell Engineering Group at the National Institute for Cellular Biotechnology (NICB) in Dublin City University aims to develop novel ways to control gene expression in Chinese Hamster Ovary (CHO) cells. One of the major challenges in the field is the lack of molecular tools to effectively manipulate the way genes are expressed. Currently available systems rely on the addition of chemicals such as antibiotics, which are a no-go in large-scale production processes, mainly due to costs, safety and regulatory issues.

My proposed novel approach to tackle this problem involves the use of microRNAs, which are small molecules responsible to regulate gene expression, as triggers to control the expression a particular gene in response to a specific factor that we can control, for instance, the temperature at which cells are grown.

In the last decade, a variety of genetic tools have been developed in the field of synthetic biology and are available. Transferring those to Chinese Hamster Ovary cells, and adapting them to react to internal cellular regulatory signals are the challenges we have ahead of us.

As part of the eCHO Systems Innovative Training Network, a collaborative EU-wide project set up by a wonderful group of CHO researchers from four academic institutions and one industrial partner, and funded by the H2020 Marie Skłodowska-Curie actions from the European Commission, it is very exciting to be adding my two cents towards developing more advanced CHO cell factories.