Enhancement of antibody production in CHO cells via Pabpc1: insights from a comparative transcriptomics study

Abstract The Chinese hamster ovary (CHO) cell line is a predominant host for the production of biopharmaceuticals due to its high capacity for recombinant protein production. However, limitations in protein secretion remain a challenge. In this study, we combined transcriptomic sequencing and fed-batch screening to identify the cytoplasmic poly(A)-binding protein gene, Pabpc1, as a positive regulator of recombinant protein expression. Stable overexpression of Pabpc1 in CHO cells producing monoclonal, bispecific, and trispecific antibodies enhanced protein titers by 30–50% without affecting cell growth, indicating its broad applicability. Co-immunoprecipitation assays revealed an interaction between PABPC1 and eIF4E in CHO cells, suggesting a potential mechanism for the improved productivity. Moreover, at the clonal level, Pabpc1 mRNA expression correlated positively with recombinant protein productivity. To our knowledge, this is the first study to demonstrate that Pabpc1 overexpression significantly enhances recombinant protein production in CHO cells across diverse antibody formats. Our findings highlight Pabpc1 as a promising target for engineering high-expression CHO cell lines and optimizing biopharmaceutical manufacturing processes. Key points • Pabpc1 is identified as a key productivity gene via comparative transcriptomics. • Pabpc1 overexpression boosts antibody yields by 30–50% in CHO cells. • This productivity enhancement is broadly effective across monoclonal and multispecific antibodies.