Dual selection system for stable therapeutic protein production


Odena Bermudo, Andreu


Therapeutic proteins have attracted great interest in the healthcare sector in recent decades thanks to their great potential to treat multiple diseases effectively and safely. Currently, the pharmaceutical industry devotes many resources to find new strategies to produce these protein products more efficiently and within this sector, cells derived from the Chinese hamster ovary (CHO) play a leading role. Currently, the selection systems used to generate CHO cell lines capable of producing large amounts of therapeutic protein are not very efficient and in many cases require a long development time.
This study is in charge of evaluating the potential of a new dual selection system as an alternative to the selection methods currently used in the pharmaceutical industry for the development of therapeutic protein-producing CHO cell lines. This new dual selection system is based on two genes, the glutamine synthetase (gs) gene and the x gene, both involved in glutamine metabolism in CHO cells. The main idea of ​​this selection system is to use a KO cell line for these two genes (GS / X-KO) in conjunction with two plasmids that code for each of the two genes in addition to the therapeutic protein of interest (GS plasmids -Enbrel and X-Enbrel) in a glutamine-deprived environment, in order to force the GS / X-KO line to integrate and amplify the plasmids thanks to the selection pressure imposed by the environment, giving rise to cell lines capable of producing large amounts of the desired therapeutic protein.
In this study, the proof of concept in charge of validating the great potential presented by this new selection system to generate cell lines with great capacity to produce therapeutic proteins has been carried out and marks a starting point to continue working on the development of this system so that in the future it can be applied to the pharmaceutical industry.



Carnicer Heras, Marc
Ebdrup Pedersen, Lasse


IQS SE - Undergraduate Program in Biotechnology