CHOgenome.org 2.0: Genome resources and website updates

Kremkow, Benjamin G.; Baik, Jong Youn; MacDonald, Madolyn L.; Lee, Kelvin H.

doi:10.1002/biot.201400646

Cited by 31 publications

(22 citation statements)

References 43 publications

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“…The model accounts for 9 compartments (cytosol, mitochondria, nucleus, endoplasmic reticulum, Golgi complex, lysosome, peroxisome, mitochondrial intermembrane space, and extracellular space) with the subcellular localization of reactions summarized in Figure 2E. The global model and reconstruction are available to browse and download at the BiGG Models Database (King et al, 2015) (http://bigg.ucsd.edu), while the three cell line models and global model are additionally hosted at http://www.CHOgenome.org (Kremkow et al, 2015). …”

Section: Resultsmentioning

confidence: 99%

“…Together, these combined efforts enabled the careful curation of this community resource. The models are available at http://www.CHOgenome.org (Kremkow et al, 2015). Additionally, the global model can be browsed and downloaded at the BiGG Models database (King et al, 2015) (accessible at http://bigg.ucsd.edu), where literature information and experimental evidence is provided for each gene, reaction, and metabolite in the model.…”

Section: Discussionmentioning

confidence: 99%

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A Consensus Genome-scale Reconstruction of Chinese Hamster Ovary Cell Metabolism

et al. 2016

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SUMMARY Chinese hamster ovary (CHO) cells dominate biotherapeutic protein production and are widely used in mammalian cell line engineering research. To elucidate metabolic bottlenecks in protein production and to guide cell engineering and bioprocess optimization, we reconstructed the metabolic pathways in CHO and associated them with >1,700 genes in the Cricetulus griseus genome. The genome-scale metabolic model based on this reconstruction, iCHO1766, and cell line-specific models for CHO-K1, CHO-S, and CHO-DG44 cells, provide the biochemical basis of growth and recombinant protein production. The models accurately predict growth phenotypes and known auxotrophies in CHO cells. With the models, we quantify the protein synthesis capacity of CHO cells and demonstrate that common bioprocess treatments, such as histone deacetylase inhibitors, inefficiently increase product yield. However, our simulations show the metabolic resources in CHO are >3 times more efficiently utilized for growth or recombinant protein synthesis following targeted efforts to engineer the CHO secretory pathway. This model will further accelerate CHO cell engineering and help optimize bioprocesses.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

A Consensus Genome-scale Reconstruction of Chinese Hamster Ovary Cell Metabolism

et al. 2016

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“…[2,3] Various smaller formats, including single chain variable fragments (scFv), antigen binding fragments (Fab), minibodies etc. [4] as well as antibody structures from alternative sources like camelid antibodies or immunoglobulin new antigen receptors [5] were investigated for their potential use as therapeutics.…”

Section: Microheterogeneitymentioning

confidence: 99%

Microheterogeneity of Recombinant Antibodies: Analytics and Functional Impact

Beyer

Schuster

Jungbauer

et al. 2017

Biotechnology Journal

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Antibodies are typical examples of biopharmaceuticals which are composed of numerous, almost infinite numbers of potential molecular entities called variants or isoforms, which constitute the microheterogeneity of these molecules. These variants are generated during biosynthesis by so‐called posttranslational modification, during purification or upon storage. The variants differ in biological properties such as pharmacodynamic properties, for example, Antibody Dependent Cellular Cytotoxicity, complement activation, and pharmacokinetic properties, for example, serum half‐life and safety. Recent progress in analytical technologies such as various modes of liquid chromatography and mass spectrometry has helped to elucidate the structure of a lot of these variants and their biological properties. In this review the most important modifications (glycosylation, terminal modifications, amino acid side chain modifications, glycation, disulfide bond variants and aggregation) are reviewed and an attempt is made to give an overview on the biological properties, for which the reports are often contradictory. Even though there is a deep understanding of cellular and molecular mechanism of antibody modification and their consequences, the clinical proof of the effects observed in vitro and in vivo is still not fully rendered. For some modifications such as core‐fucosylation of the N‐glycan and aggregation the effects are clear and should be monitored, but with others such as C‐terminal lysine clipping the reports are contradictory. As a consequence it seems too early to tell if any modification can be safely ignored.

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“…Chinese hamster ovary (CHO) cells are widely used for the commercial production of therapeutic proteins including antibodies . For high‐level expression of therapeutic proteins in CHO cell cultures, cell proliferation is often controlled by limiting the progression of the cell cycle by genetic manipulation of cell cycle checkpoints , hypothermic or hyperosmolar culture conditions , or chemical agents , because this growth arrest can significantly increase specific productivity ( q p ) .…”

Section: Introductionmentioning

confidence: 99%

Valeric acid induces cell cycle arrest at G1 phase in CHO cell cultures and improves recombinant antibody productivity

Park

Noh

Woo³

et al. 2015

Biotechnology Journal

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To find a more effective chemical reagent for improved monoclonal antibody (mAb) production, eight chemical reagents (curcumin, quercein, DL-sulforaphane, thymidine, valeric acid, phenyl butyrate, valproic acid, and lithium chloride) known to induce cell cycle arrest were examined individually as chemical additives to recombinant CHO (rCHO) cell cultures producing mAb. Among these chemical additives, valeric acid showed the best production performance. Valeric acid decreased specific growth rate (μ), but increased culture longevity and specific mAb productivity (qmAb ) in a dose-dependent manner. The beneficial effect of valeric acid on culture longevity and qmAb outweighed its detrimental effect on μ, resulting in 2.9-fold increase in the maximum mAb concentration when 1.5 mM valeric acid was added to the cultures. Furthermore, valeric acid did not negatively affect the mAb quality attributes with regard to aggregation, charge variation, and galactosylation. Unexpectedly, galactosylation of the mAb increased by the 1.5 mM valeric acid addition. Taken together, the results obtained here demonstrate that valeric acid is an effective chemical reagent to increase mAb production in rCHO cells.

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CHOgenome.org 2.0: Genome resources and website updates

Cited by 31 publications

References 43 publications

A Consensus Genome-scale Reconstruction of Chinese Hamster Ovary Cell Metabolism

A Consensus Genome-scale Reconstruction of Chinese Hamster Ovary Cell Metabolism

Microheterogeneity of Recombinant Antibodies: Analytics and Functional Impact

Valeric acid induces cell cycle arrest at G1 phase in CHO cell cultures and improves recombinant antibody productivity

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