期刊
BIOTECHNOLOGY LETTERS
卷 43, 期 8, 页码 1551-1563出版社
SPRINGER
DOI: 10.1007/s10529-021-03153-7
关键词
Chinese hamster ovary (CHO) cells; MiRNA; Label free quantitative proteomics; Cell specific productivity (Qp); Biopharmaceuticals
资金
- Irish Research Council Enterprise Partnership Scheme [EPSPG/2016/10]
- Science Foundation Ireland (SFI) Infrastructure Award [16/RI/3701]
- IReL Consortium
- Irish Research Council (IRC) [EPSPG/2016/10] Funding Source: Irish Research Council (IRC)
- Science Foundation Ireland (SFI) [16/RI/3701] Funding Source: Science Foundation Ireland (SFI)
The study identified miR-200a as a potential regulator of the unfolded protein response (UPR) in CHO cells, affecting protein folding and impacting Qp phenotype, suggesting it as a potential target for engineering industrially attractive CHO cell phenotypes.
Objectives We used miRNA and proteomic profiling to understand intracellular pathways that contribute to high and low specific productivity (Qp) phenotypes in CHO clonally derived cell lines (CDCLs) from the same cell line generation project. Results Differentially expressed (DE) miRNAs were identified which are predicted to target several proteins associated with protein folding. MiR-200a was found to have a number of predicted targets associated with the unfolded protein response (UPR) which were shown to have decreased expression in high Qp CDCLs and have no detected change at the mRNA level. MiR-200a overexpression in a CHO CDCL was found to increase recombinant protein titer by 1.2 fold and Qp by 1.8 fold. Conclusion These results may suggest a role for miR-200a in post-transcriptional regulation of the UPR, presenting miR-200a as a potential target for engineering industrially attractive CHO cell phenotypes.
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