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Cell function profiling to assess clone stability

delete2020-04-10
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OA
AI
P
Paul D. Dobson *
K
Karen P. Coss
C
Carolanne Doherty
J
Jerry Clifford
B
Ben Thompson
D
David C. James
DOI:10.1002/bit.27336delete
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Abstract

Abstract

En 中文
In cell line development the identification of stable Chinese hamster ovary cells for production is a critical but onerous task. The stability trial focus upon high-level attributes can mask profound underlying cellular changes, leading to unstable clones mistakenly being chosen for production. The challenge is to assay underlying cell pathways and subsystems without pushing up cell line development costs. ChemStress (R) cell function profiling is a simple, multiwell plate-based assay that uses a panel of active chemicals to mimic known bioprocess stresses and challenge key pathways. After 3 days of static culture on the plate, functional responses are assayed, for example, titer and growth. Here this approach is used to monitor 131 clones as they change over real stability trials. A novel stability metric is defined over the data to identify stable clones that remain unperturbed across many components of cell function. This allows stability trials to look beneath the titer to identify clones that are internally more stable.
Keywords:
bioprocessing
cell function
CHO
clone stability
monitoring
phenotyping
process
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Journal

Biotechnology and Bioengineering cover
Biotechnology and Bioengineering
IF:
3.6
Papers:
9.8K
Citations:
2.2W

Organization

U
University of Sheffield
Scholars:
3.0W
Papers: 2.9W
Citations: 3.9W