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Duplication of a chromosome 2 segment in production CHO cell lines correlates with age-related growth improvement
Wei Wei1, Laura Zielewicz1, Lin Zhang1,2
1Cell Line Development, Biotherapeutics Pharmaceutical Sciences, Pfizer Inc, Andover, Massachusetts, USA.
Biotechnology Journal
|February 25, 2024
Summary
Recombinant Chinese Hamster Ovary (CHO) cell lines can unexpectedly improve growth with age. This study identifies a specific 50.2 Mbp duplication on chromosome 2 (Chr2) as the cause of this age-correlated growth change in CHO cell lines.
Area of Science:
- Biotechnology
- Genomics
- Cell Biology
Background:
- Recombinant Chinese Hamster Ovary (CHO) cell line stability is critical for biomanufacturing.
- Age-correlated phenotypic changes, like accelerated growth, are observed in CHO cell lines but poorly understood.
- Investigating the molecular basis of these changes is essential for optimizing cell line development.
Purpose of the Study:
- To elucidate the molecular mechanisms behind age-correlated cell growth improvement in recombinant CHO cell lines.
- To identify genetic alterations associated with enhanced growth in aged CHO cell cultures.
- To understand the role of genomic changes in CHO cell line stability during biomanufacturing.
Main Methods:
- Whole-genome resequencing of multiple CHO cell lines expressing monoclonal antibodies (mAbs).
- Comparative analysis of cell lines exhibiting age-correlated growth changes versus those without.
- Transcriptome profiling to identify differentially expressed genes between high-growth and low-growth cell lines.
Main Results:
- A specific 50.2 Mbp segment duplication on chromosome 2 (Chr2) was identified in CHO clones with age-correlated growth improvement.
- This Chr2 duplication was independent of the type of monoclonal antibody expressed.
- >95% of overexpressed genes in high-growth cell lines were located within the duplicated Chr2 segment.
Conclusions:
- Large genomic duplication on Chr2 is associated with age-correlated growth changes in recombinant CHO cell lines.
- This finding represents the first report linking Chr2 duplication to enhanced growth in aged CHO cells.
- Further research will focus on the causal relationship between Chr2 genes and growth changes, aiming to improve cell line screening and engineering for stability.
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