Combining regulated and constitutive protein expression significantly boosts protein expression by increasing productivity without affecting CHO cell growth
In this study, combinations of regulated and constitutive expression systems were used to supertransfect targeted integration (TI) cell lines expressing the same antibody either constitutively or under-regulated expression. Clone screening with a hybrid expression system (inducible + constitutive) allowed identification and selection of higher titer clones under uninduced conditions, without a negative impact on cell growth during clone selection and expansion. Induction of the regulated promoter(s) during the production phase increased the Qp without negatively affecting growth, resulting in approximately twofold higher titers (from 3.5 to 6 –7 g/L). This was also confirmed using a 2-site TI host where the gene of interest was expressed inducibly from Site 1 and constitutively from Site 2. Our findings suggest that such a hybrid expression CLD system can be used to increase production titers, providing a novel approach for expression of therapeutic proteins with high titer market demands.
Source: Biotechnology Progress - Category: Biotechnology Authors: Cynthia Lam,
Joseph Carver,
Domingos Ng,
Dejin Zhan,
Danming Tang,
Thara Kandamkalam,
Brad Snedecor,
Gavin Barnard,
Amy Shen,
Shahram Misaghi Tags: RESEARCH ARTICLE Source Type: research