Use of tRNA gene barriers improves stability of transgene expression in CHO cells

Rebecca Sizer; Richard Ingram; Caroline Swann; Emma Biggs; Leon P Pybus; Bob White

doi:10.1002/biot.202400196

Use of tRNA gene barriers improves stability of transgene expression in CHO cells

Rebecca Sizer, Richard Ingram, Caroline Swann, Emma Biggs, Leon P Pybus, Bob White

Biology

Research output: Contribution to journal › Article › peer-review

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

Original language	English
Article number	2400196
Number of pages	11
Journal	Biotechnology journal
Volume	19
Issue number	8
DOIs	https://doi.org/10.1002/biot.202400196
Publication status	Published - 8 Aug 2024

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10.1002/biot.202400196Licence: CC BY

Biotechnology Journal - 2024 - Sizer - Use of tRNA gene barriers improves stability of transgene expression in CHO cells
© 2024 The Author(s)
Final published version, 1.06 MBLicence: CC BY

Cite this

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AU - Swann, Caroline

AU - Biggs, Emma

AU - Pybus, Leon P

AU - White, Bob

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