دورية أكاديمية
Mitochondrial membrane potential-enriched CHO host: a novel and powerful tool for improving biomanufacturing capability.
| العنوان: | Mitochondrial membrane potential-enriched CHO host: a novel and powerful tool for improving biomanufacturing capability. |
|---|---|
| المؤلفون: | Chakrabarti L; Cell Culture & Fermentation Sciences, BioPharmaceuticals Development, R&D, AstraZeneca, Gaithersburg, MD, USA., Chaerkady R; Dynamic Omics, Discovery Sciences, R&D, AstraZeneca, Gaithersburg, MD, USA., Wang J; Dynamic Omics, Discovery Sciences, R&D, AstraZeneca, Gaithersburg, MD, USA., Weng SHS; Dynamic Omics, Discovery Sciences, R&D, AstraZeneca, Gaithersburg, MD, USA., Wang C; Analytical Sciences, BioPharmaceuticals Development, R&D, AstraZeneca, Gaithersburg, MD, USA., Qian C; Analytical Sciences, BioPharmaceuticals Development, R&D, AstraZeneca, Gaithersburg, MD, USA., Cazares L; Dynamic Omics, Discovery Sciences, R&D, AstraZeneca, Gaithersburg, MD, USA., Hess S; Dynamic Omics, Discovery Sciences, R&D, AstraZeneca, Gaithersburg, MD, USA., Amaya P; Cell Culture & Fermentation Sciences, BioPharmaceuticals Development, R&D, AstraZeneca, Gaithersburg, MD, USA., Zhu J; Cell Culture & Fermentation Sciences, BioPharmaceuticals Development, R&D, AstraZeneca, Gaithersburg, MD, USA., Hatton D; Cell Culture & Fermentation Sciences, BioPharmaceuticals Development, R&D, AstraZeneca, Cambridge, UK. |
| المصدر: | MAbs [MAbs] 2022 Jan-Dec; Vol. 14 (1), pp. 2020081. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't; Video-Audio Media |
| اللغة: | English |
| بيانات الدورية: | Publisher: Taylor & Francis Country of Publication: United States NLM ID: 101479829 Publication Model: Print Cited Medium: Internet ISSN: 1942-0870 (Electronic) Linking ISSN: 19420862 NLM ISO Abbreviation: MAbs Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 2015- : Philadelphia, PA : Taylor & Francis Original Publication: Austin, TX : Landes Bioscience |
| مواضيع طبية MeSH: | Metabolic Engineering*, Membrane Potential, Mitochondrial/*genetics , Mitochondria/*genetics , Mitochondria/*metabolism, Animals ; CHO Cells ; Cricetulus |
| مستخلص: | With the aim of increasing protein productivity of Chinese hamster ovary (CHO) cells, we sought to generate new CHO hosts with favorable biomanufacturing phenotypes and improved functionality. Here, we present an innovative approach of enriching the CHO host cells with a high mitochondrial membrane potential (MMP). Stable transfectant pools and clonal cell lines expressing difficult-to-express bispecific molecules generated from the MMP-enriched host outperformed the parental host by displaying (1) improved fed-batch productivity; (2) enhanced long-term cell viability of pools; (3) more favorable lactate metabolism; and (4) improved cell cloning efficiency during monoclonal cell line generation. Proteomic analysis together with Western blot validation were used to investigate the underlying mechanisms by which high MMP influenced production performance. The MMP-enriched host exhibited multifaceted protection against mitochondrial dysfunction and endoplasmic reticulum stress. Our findings indicate that the MMP-enriched host achieved an overall "fitter" phenotype that contributes to the significant improvement in biomanufacturing capability. |
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| فهرسة مساهمة: | Keywords: CHO; cell line development; cell sorting; enrichment; mitochondrial membrane potential; productivity; proteomics |
| تواريخ الأحداث: | Date Created: 20220115 Date Completed: 20220329 Latest Revision: 20220329 |
| رمز التحديث: | 20240628 |
| مُعرف محوري في PubMed: | PMC8765075 |
| DOI: | 10.1080/19420862.2021.2020081 |
| PMID: | 35030984 |
| قاعدة البيانات: | MEDLINE |
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