Next-Generation Sequencing: a powerful multi-purpose tool in cell line development for biologics production

Abstract

Within the biopharmaceutical industry, the cell line development (CLD) process generates recombinant mammalian cell lines for the expression of therapeutic proteins. Analytical methods for the extensive characterisation of the protein product are well established; however, over recent years, next-generation sequencing (NGS) technologies have rapidly become an integral part of the CLD workflow. NGS can be used for different applications to characterise the genome, epigenome and transcriptome of cell lines. The resulting extensive datasets, especially when integrated with systems biology models, can give comprehensive insights that can be applied to optimize cell lines, media, and fermentation processes. NGS also provides comprehensive methods to monitor genetic variability during CLD. High coverage NGS experiments can indeed be used to ensure the integrity of plasmids, identify integration sites, and verify monoclonality of the cell lines. This review summarises the role of NGS in advancing biopharmaceutical production to ensure safety and efficacy of therapeutic proteins.