Transcriptomic variation between different Chinese hamster ovary cell lines

Blas, Marjanca; Francky, Andrej; Jamnikar, Uros; Gaser, Dominik; Baebler, Špela; Blejec, Andrej; Gruden, Kristina

doi:10.1007/s10529-015-1850-0

Cited by 5 publications

(4 citation statements)

References 16 publications

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“…A recent paper presented images of single karyotypes derived from metaphase spreads prepared with cells of five CHO host cell lines (two K1-derived, two DUXB11-and one DG44-derived cell population) [17]. The authors found these cell lines showing a large diversity of genotypes (pseudo-diploid, pseudo triploid, mixed pseudo diploid and triploid) with highly variable chromosomal structures.…”

Section: Chromosomal and Genomic Heterogeneity Of Cho Cells Other Cementioning

confidence: 99%

Cloning of CHO Cells, Productivity and Genetic Stability—A Discussion

Wurm

Wurm²

2017

Processes

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While many perceive mammalian cell culture-based manufacturing for biopharmaceuticals an established technology, numerous open questions remain to be solved. Genetic diversity and mutation rates in CHO cells have been underestimated since progeny of a clonal CHO cell become genetically diverse with each cell division. This is an important issue since products are made in bioreactors containing up to 10 14 cells that have divided for weeks. Regulatory interest in "Proof of Clonality" is a misguided and misunderstood concern in this context. We revisit decades of research on scope and rate of genetic changes in CHO cells and suggest approaches to minimize trends for genomic instability when establishing reliable manufacturing processes. A concept is proposed for transfection-derived cell populations containing relatively stable (The term "stable" will always be used in a context of relative stability-considering time frames of weeks to months at best.) "CHO master sequence" genomes (containing the desired DNAs of interest). Stable cell populations are to be selected for and maintained for the various phases of manufacturing under specific culture conditions reducing trends for the selection of diverse subpopulations. Such conditions are based on insights gained from population genetics, evolutionary landscape fitness principles, and a 40-year old model for evolution of error prone replicating systems-the Quasi-Species concept.

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Section: Chromosomal and Genomic Heterogeneity Of Cho Cells Other Cementioning

confidence: 99%

Cloning of CHO Cells, Productivity and Genetic Stability—A Discussion

Wurm

Wurm²

2017

Processes

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“…Transcriptomics involves the analysis of gene expression levels under different conditions in an effort to reveal cellular mechanisms, response to environmental changes, treatments, and mechanisms of action. Applications in CHO bioprocessing include identification of cellular pathways and responses to varying conditions in order to optimize productivity and therapeutic product quality …”

Section: Transcriptomicsmentioning

confidence: 99%

“…Using Roche 454 sequencing technology and the Newbler Assembler, Becker et al assembled 1.84 million reads of several CHO cell lines and reconstructed metabolic pathways of the central carbohydrate metabolism and biosynthesis routes of sugars used for protein N‐glycosylation, enabling targeted pathway engineering for improved bioprocess characteristics . While Blas et al identified cell line specific markers by microarrays with the aim to use the markers in cell line development, Vishwanathan et al used RNA‐Seq data from 6 CHO cell lines and constructed microarrays to identify major functional pathways. The information gathered around variability with regard to growth, metabolism, and product consistency could be used for cell line engineering .…”

Section: Transcriptomicsmentioning

confidence: 99%

“…Applications in CHO bioprocessing include identification of cellular pathways and responses to varying conditions in order to optimize productivity and therapeutic product quality. [48,49] Quantitative reverse transcription polymerase chain reaction (qRT-PCR) is widely used to measure gene expression for smallscale studies involving a subset of genes or to confirm targets from high-throughput experiments and is limited by requiring mRNA sequence information to design probes. [50] Techniques for gathering high-throughput transcriptomic data include microarrays and RNA-Seq.…”

Section: Transcriptomicsmentioning

confidence: 99%

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CHO‐Omics Review: The Impact of Current and Emerging Technologies on Chinese Hamster Ovary Based Bioproduction

Stolfa

Smonskey

Boniface

et al. 2017

Biotechnology Journal

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CHO cells are the most prevalent platform for modern bio-therapeutic production. Currently, there are several CHO cell lines used in bioproduction with distinct characteristics and unique genotypes and phenotypes. These differences limit advances in productivity and quality that can be achieved by the most common approaches to bioprocess optimization and cell line engineering. Incorporating omics-based approaches into current bioproduction processes will complement traditional methodologies to maximize gains from CHO engineering and bioprocess improvements. In order to highlight the utility of omics technologies in CHO bioproduction, the authors discuss current applications as well as limitations of genomics, transcriptomics, proteomics, metabolomics, lipidomics, fluxomics, glycomics, and multi-omics approaches and the potential they hold for the future of bioproduction. Multiple omics approaches are currently being used to improve CHO bioprocesses; however, the application of these technologies is still limited. As more CHO-omic datasets become available and integrated into systems models, the authors expect significant gains in product yield and quality. While individual omics technologies provide incremental improvements in bioproduction, the authors will likely see the most significant gains by applying multi-omics and systems biology approaches to individual CHO cell lines.

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