4.5 Article

Stable overexpression of miR-17 enhances recombinant protein production of CHO cells

Journal

JOURNAL OF BIOTECHNOLOGY
Volume 175, Issue -, Pages 38-44

Publisher

ELSEVIER
DOI: 10.1016/j.jbiotec.2014.01.032

Keywords

Chinese hamster ovary (CHO) cells; microRNA (miRNA); miR-17; miR-92a; miR17-92a cluster; Productivity

Funding

  1. FWF doctorate program BioTop [W1224]
  2. Austrian Center of Industrial Biotechnology
  3. Austrian FFG
  4. BOKU Doc grant

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miRNAs negatively regulate gene expression at post-transcriptional level, and consequently play an important role in the control of many cellular pathways. The use of miRNAs to engineer Chinese hamster ovary (CHO) cells is an emerging strategy to improve recombinant protein production. Here, we describe the effect of transient and stable miRNA overexpression on CHO cell phenotype. Using an established transient miRNA screening protocol, the effects of miR-17, miR-92a and cluster miR17-92a on CHO growth and protein productivity were studied and followed by analysis of cell pools with stable overexpression of these miRNAs. CHO cells stably engineered with miR-17 exhibited both enhanced growth performance and a 2-fold increase in specific productivity, which resulted in a 3-fold overall increase in EpoFc titer. While further studies of miRNA-mRNA interactions will be necessary to understand the molecular basis of this effect, these data provide valuable evidence for miR-17 as a cell engineering target to enhance CHO cell productivity. (C) 2014 The Authors. Published by Elsevier B.V. All rights reserved.

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