Sizer, Rebecca, Ingram, Richard, Swann, Caroline et al. (3 more authors) (2024) Use of tRNA gene barriers improves stability of transgene expression in CHO cells. Biotechnology journal. 2400196. ISSN 1860-7314
Abstract
Instability of transgene expression is a major challenge for the biopharmaceutical industry, which can impact yields and regulatory approval. Some tRNA genes (tDNAs) can resist epigenetic silencing, the principal mechanism of expression instability, and protect adjacent genes against the spread of repressive heterochromatin. We have taken two naturally occurring clusters of human tDNAs and tested their ability to reduce epigenetic silencing of transgenes integrated into the genome of Chinese hamster ovary (CHO) cells. We find sustained improvements in productivity both in adherent CHO-K1 cells and in an industrially relevant CHO-DG44 expression sys- tem (Apollo X, FUJIFILM Diosynth Biotechnologies). We conclude that specific tDNA clusters offer potential to mitigate the widespread problem of production instability
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2024 The Author(s) |
Dates: |
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Institution: | The University of York |
Academic Units: | The University of York > Faculty of Sciences (York) > Biology (York) |
Depositing User: | Pure (York) |
Date Deposited: | 05 Mar 2025 08:50 |
Last Modified: | 05 Mar 2025 08:50 |
Published Version: | https://doi.org/10.1002/biot.202400196 |
Status: | Published |
Refereed: | Yes |
Identification Number: | 10.1002/biot.202400196 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:224057 |
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Description: Biotechnology Journal - 2024 - Sizer - Use of tRNA gene barriers improves stability of transgene expression in CHO cells
Licence: CC-BY 2.5