Masayoshi Onitsuka

Highlights • A method to detect intracellular non-native antibody aggregates was established • The formation, dynamics, and degradation of intracellular aggregates was visualized • Correlation between intra- and extracellular aggregates suggests direct secretion • This work represents progress toward high-quality production of therapeutic antibodies by aggregate minimization Summary Recombinant immunoglobulin G (IgG) aggregates are formed during their production.

Several engineering strategies have been employed to improve the production of therapeutic recombinant proteins in Chinese hamster ovary (CHO) cell lines. We have focused on unfolded protein response-based engineering and reported that ATF4 overexpression increases protein production. In this study, transcriptome analysis of ATF4-overexpressed CHO cells was performed using high-coverage expression profiling, to search for another key factor contributing to recombinant protein production.