Mitochondrial membrane potential-enriched CHO host: a novel and powerful tool for improving biomanufacturing capability
| Autor: | Lina Chakrabarti, Raghothama Chaerkady, Junmin Wang, Shao Huan Samuel Weng, Chunlei Wang, Chen Qian, Lisa Cazares, Sonja Hess, Peter Amaya, Jie Zhu, Diane Hatton |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2022 |
| Předmět: |
Membrane Potential
Mitochondrial enrichment productivity cho Immunology cell line development CHO Cells RM1-950 RC581-607 Mitochondria Cricetulus mitochondrial membrane potential proteomics Metabolic Engineering Report Animals Immunology and Allergy Therapeutics. Pharmacology Immunologic diseases. Allergy cell sorting |
| Zdroj: | mAbs, Vol 14, Iss 1 (2022) mAbs article-version (VoR) Version of Record |
| ISSN: | 1942-0870 1942-0862 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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