New Mammalian Expression Systems

Abstract

There are an increasing number of recombinant antibodies and proteins in preclinical and clinical development for therapeutic applications. Mammalian expression systems are key to enabling the production of these molecules, and Chinese hamster ovary (CHO) cell platforms continue to be central to delivery of the stable cell lines required for large-scale production. Increasing pressure on timelines and efficiency, further innovation of molecular formats and the shift to new production systems are driving developments of these CHO cell line platforms. The availability of genome and transcriptome data coupled with advancing gene editing tools are increasing the ability to design and engineer CHO cell lines to meet these challenges. This chapter aims to give an overview of the developments in CHO expression systems and some of the associated technologies over the past few years.

Exploring the limits of conventional small-scale CHO fed-batch for accelerated on demand monoclonal antibody production

“…The preferential mammalian system of expression of biopharmaceuticals are the Chinese Hamster Ovary cells (CHO) for their ability to perform post-translational modifications close to human, its efficient protein folding and its delivery of high productivity [3][4][5]. Over the last 2 decades, expression of mAbs in CHO has been greatly improved and volumetric titers of 10 g/L in 14-18 days can now be achieved [6][7][8][9].…”

Hybridoma technology: is it still useful?

“…This restriction can be overcome by mRNA and ribosome display strategies, which are in vitro cell-free methods having a bigger library size and a higher displayed antibody diversity (10 14 variants) ( Hudson and Souriau, 2003 ; Kunamneni et al., 2020 ). It should be also considered that phage display-selected mAbs are generated in E. coli and therefore are not glycosylated; the use of eukaryotic display platforms, like yeast ( Doerner et al., 2014 ) and mammalian expression systems ( Zhu and Hatton, 2017 ), is a possibility to circumvent that. Other antibody phage display methodology disadvantages are the propensity to generate biased repertoires and the loss of information of antibody natural pairing ( Saggy et al., 2012 ) ( Table 1 ).…”

DetectIS: a pipeline to rapidly detect exogenous DNA integration sites using DNA or RNA paired-end sequencing data

“…Recombinant DNA technology can be used to generate transgenic animals, plants and cell lines, widely used for different applications in biology, medicine and biotechnology ( Ghaderi et al , 2012 ; Khan et al , 2016 ). Therapeutic proteins with complex post-translational modifications are normally expressed in mammalian cell lines ( Walsh, 2018 ; Zhu and Hatton, 2018 ). Viral transduction and plasmid transfection are methods largely used to establish recombinant cell lines ( Kim and Eberwine, 2010 ; Lee et al ., 2018 ) and typically result in random integration of the transgene construct into the host genome.…”