ArticleBiotechnology and bioengineering2019
Recurring genomic structural variation leads to clonal instability and loss of productivity.
Article in Biotechnology and bioengineering, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed.
- Establishment and longitudinal characterisation of a feeder-free embryonic stem-like cell line (ATES1) derived from blastomeres of the climbing perch, Anabas testudineus.Fish physiology and biochemistry · 2026Article
- Delineating the Transcriptional and Phenotypic Impact from Biotherapeutic Glycoengineering.bioRxiv : the preprint server for biology · 2026Article
- Transgene Mapping in Animals: What to Choose?International journal of molecular sciences · 2025Review
- From Cell Clones to Recombinant Protein Product Heterogeneity in Chinese Hamster Ovary Cell Systems.International journal of molecular sciences · 2025Review
- Next-generation sequencing: A powerful multi-purpose tool in cell line development for biologics production.Computational and structural biotechnology journal · 2025Review
- Microevolutionary dynamics of eccDNA in Chinese hamster ovary cells grown in fed-batch cultures under control and lactate-stressed conditions.Scientific reports · 2023Article
- Restoration of DNA repair mitigates genome instability and increases productivity of Chinese hamster ovary cells.Biotechnology and bioengineering · 2022Article
- Structural analysis of random transgene integration in CHO manufacturing cell lines by targeted sequencing.Biotechnology and bioengineering · 2022Article
- Rational design and construction of multi-copy biomanufacturing islands in mammalian cells.Nucleic acids research · 2022Article
- Enhancing stability of recombinant CHO cells by CRISPR/Cas9-mediated site-specific integration into regions with distinct histone modifications.Frontiers in bioengineering and biotechnology · 2022Article
- Genetic rearrangement during site specific integration event facilitates cell line development of a bispecific molecule.Biotechnology progress · 2021Article
- Violacein improves recombinant IgG production by controlling the cell cycle of Chinese hamster ovary cells.Cytotechnology · 2021Article
- DNA Double-Strand Breaks Affect Chromosomal Rearrangements during Methotrexate-Mediated Gene Amplification in Chinese Hamster Ovary Cells.Pharmaceutics · 2021Article
- Chinese hamster ovary cell line DXB-11: chromosomal instability and karyotype heterogeneity.Molecular cytogenetics · 2021Article
- PTSelect™: A post-transcriptional technology that enables rapid establishment of stable CHO cell lines and surveillance of clonal variation.Journal of biotechnology · 2021Article
- Characterization of metabolic responses, genetic variations, and microsatellite instability in ammonia-stressed CHO cells grown in fed-batch cultures.BMC biotechnology · 2021Article
- Cell culture bioprocessing - the road taken and the path forward.Current opinion in chemical engineering · 2020Article
- Multiplexed clonality verification of cell lines for protein biologic production.Biotechnology progress · 2020Article
- Predicting favorable landing pads for targeted integrations in Chinese hamster ovary cell lines by learning stability characteristics from random transgene integrations.Computational and structural biotechnology journal · 2020Article
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6 authors.
Funding
Abstract
Chinese hamster ovary cells, commonly used in the production of therapeutic proteins, are aneuploid. Their chromosomes bear structural abnormality and undergo changes in structure and number during cell proliferation. Some production cell lines are unstable and lose their productivity over time in the manufacturing process and during the product's life cycle. To better understand the link between genomic structural changes and productivity stability, an immunoglobulin G producing cell line was successively single-cell cloned to obtain subclones that retained or lost productivity, and their genomic features were compared. Although each subclone started with a single karyotype, the progeny quickly diversified to a population with a distribution of chromosome numbers that is not distinctive from the parent and among subclones. The comparative genomic hybridization (CGH) analysis showed that the extent of copy variation of gene coding regions among different subclones stayed at levels of a few percent. Genome regions that were prone to loss of copies, including one with a product transgene integration site, were identified in CGH. The loss of the transgene copy was accompanied by loss of transgene transcript level. Sequence analysis of the host cell and parental producing cell showed prominent structural variations within the regions prone to loss of copies. Taken together, we demonstrated the transient nature of clonal homogeneity in cell line development and the retention of a population distribution of chromosome numbers; we further demonstrated that structural variation in the transgene integration region caused cell line instability. Future cell line development may target the transgene into structurally stable regions.
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