Assessment of the influence of chromatin elements on stability of recombinant protein production in amplified CHO cells
Zeynep Betts, PhD
Manchester University, UK
Date &Time: August 8th, 2012 – 14.30
Place: FENS 2008
Key Words: Gene expression, recombinant proteins, CHO, mammalian system
Therapeutic proteins require proper folding and post-translational modifications (PTMs) to be effective and biologically active. Chinese hamster ovary (CHO) cells are the most frequently used host for commercial production of therapeutic proteins and DHFR-mediated gene amplification is extensively applied to generate cell lines with increased protein production. However, decreased protein productivity is observed unpredictably during the time required for scale-up with consequences for yield, time, finance and regulatory approval. Ubiquitous Chromatin Opening Elements (UCOEs) are DNA elements naturally found upstream of specific housekeeping genes, which are proposed to maintain open chromatin structure, supporting stable and high-level transgene expression by prevention of transgene silencing. In this study we have examined the interaction between UCOE and DHFR-linked amplification in relation to cell expression stability.