Method for increasing the cell-specific productivity of production cell lines through targeted irradiation with blue light
Abstract
The targeted use of blue light can significantly increase the productivity of protein-producing production cells without the need for genetic modifications or the use of certain chemicals.
Advantages
- Significant increase in productivity
- Broad applicability for different cell lines
- Non-invasive method
- Simple technical implementation using commercially available LEDs and inexpensive microcontrollers
- No genetic modifications of the cell lines necessary
- No cell culture additives necessary
- Productivity of existing cell culture systems with ATF perfusion module can be easily increased without retrofitting
Fields of application
- Increasing the productivity of existing cell culture systems to increase the product yield with simple means
- Production of proteins in cell culture that previously could not be produced at all or only with great effort
Background
Biopharmaceutical drugs are playing an increasingly important role in diagnostics and therapy. In contrast to the chemical synthesis of active substances and drugs, biopharmaceuticals are produced biotechnologically with the help of cells kept in bioreactors. In particular, so-called therapeutic monoclonal antibodies can be produced in this way, enabling new approaches and targeted treatment options for a variety of diseases (especially cancer). However, the production of these diverse active substances using cell culture systems is complex and requires specific know-how as well as special technologies and equipment.
Problem
Various methods are used in the field of cell culture technology to increase production rates and yields. Common methods include the use of chemicals (such as sodium butyrate), the use of certain genetic elements or the adjustment of physical cultivation conditions (such as temperature, pH value, osmolarity). However, such approaches quickly reach the technical limits of bioreactors, are invasive or impair the processing of the product from the culture supernatant. There is therefore a need for new methods to increase the productivity of production cells in the manufacture of biopharmaceuticals, especially those that are non-invasive, do not require the addition of substances to the cell culture and do not require genetic modification of the cells.
Solution
To overcome the challenges described above, an innovative method was developed at the University of Stuttgart to significantly increase the protein production of eukaryotic cell cultures. The scientists exploited a surprising and unexpected effect of blue light on cells during the production phase. Surprisingly, it was found that blue light under certain intensities and wavelengths has no harmful or killing effect on the cells, but - on the contrary - enables a considerable increase in productivity. It is also surprising that no special optogenetic elements or cell culture additives are required for light sensitivity. This facilitates the application of the method to new proteins and existing cell culture systems as well as the subsequent purification of the protein product. In laboratory tests with CHO cells, a significant increase in productivity of 50-70% was achieved by using the new method. The new method can be used for common production cell lines such as CHO as well as HEK, COS or HeLa cells.
Figure 1: Implementation of LED lighting on a commercially available reactor on a 3 L laboratory scale with ATF perfusion module. (Figure 1: R. Takors, Institute of Bioprocess Engineering, University of Stuttgart)
Publications and links
In Vorbereitung