A blueprint from nature: miRNome comparison of plasma cells and CHO cells to optimize therapeutic antibody production.

Autor: Raab N; Institute of Applied Biotechnology, Biberach University of Applied Sciences, Biberach, Germany., Zeh N; Institute of Applied Biotechnology, Biberach University of Applied Sciences, Biberach, Germany., Schlossbauer P; Institute of Applied Biotechnology, Biberach University of Applied Sciences, Biberach, Germany., Mathias S; Institute of Applied Biotechnology, Biberach University of Applied Sciences, Biberach, Germany; Early Stage Bioprocess Development, Bioprocess Development Biologicals, Boehringer Ingelheim GmbH & Co KG, Biberach, Germany., Lindner B; Cell Line Development, Bioprocess Development Biologicals, Boehringer Ingelheim GmbH & Co KG, Biberach, Germany., Stadermann A; Cell Line Development, Bioprocess Development Biologicals, Boehringer Ingelheim GmbH & Co KG, Biberach, Germany., Gamer M; Cell Line Development, Bioprocess Development Biologicals, Boehringer Ingelheim GmbH & Co KG, Biberach, Germany., Fischer S; Cell Line Development, Bioprocess Development Biologicals, Boehringer Ingelheim GmbH & Co KG, Biberach, Germany., Holzmann K; Genomics Core Facility, Medical Faculty, Ulm University, Ulm, Germany., Handrick R; Institute of Applied Biotechnology, Biberach University of Applied Sciences, Biberach, Germany., Otte K; Institute of Applied Biotechnology, Biberach University of Applied Sciences, Biberach, Germany. Electronic address: otte@hochschule-bc.de.
Jazyk: angličtina
Zdroj: New biotechnology [N Biotechnol] 2022 Jan 25; Vol. 66, pp. 79-88. Date of Electronic Publication: 2021 Oct 25.
DOI: 10.1016/j.nbt.2021.10.005
Abstrakt: Chinese Hamster Ovary (CHO) cells are the most frequently used biopharmaceutical production hosts, although industry is presently suffering from their variable recombinant product quality, insufficient long-term stability and low productivity. Here, we present an effort to address overall cell line engineering by a novel bottom-up microRNA (miRNA) screening approach. miRNAs are small non-coding RNAs known to regulate global gene expression at the post-transcriptional level and have proved to serve as promising tools for cell line engineering for over a decade. Here the miRNome of plasma cells (PCs) has been analyzed as the natural blueprint for optimized production and secretion of antibodies. Performing comparative miRNome cross-species expression analysis of four murine/human PC-derived (PCD) and two CHO cell lines showed 147 conserved miRNAs to be differentially expressed between PCDs and CHOs. Conducting a targeted miRNA screen of this PC-specific miRNA subset revealed 14 miRNAs to improve bioprocess relevant parameters in CHO cells, among them the PC-characteristic miR-183 cluster. Finally, miRNA target prediction tools and transcriptome analysis were combined to elucidate differentially regulated lysine degradation and fatty acid metabolism pathways in monoclonal antibody (mAb) expressing CHO-DG44 and CHO-K1 cells, respectively. Thus, substantial new insights into molecular and cellular mechanisms of biopharmaceutical production cell lines can be gained by targeted bottom-up miRNA screenings.
(Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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