Mitochondrial membrane potential-enriched CHO host: a novel and powerful tool for improving biomanufacturing capability.
MAbs
; 14(1): 2020081, 2022.
Article
de En
| MEDLINE
| ID: mdl-35030984
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.
Mots clés
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Potentiel de membrane mitochondriale
/
Génie métabolique
/
Mitochondries
Limites:
Animals
Langue:
En
Journal:
MAbs
Sujet du journal:
ALERGIA E IMUNOLOGIA
Année:
2022
Type de document:
Article
Pays d'affiliation:
États-Unis d'Amérique
Pays de publication:
États-Unis d'Amérique