Improving the secretory capacity of Chinese hamster ovary cells by ectopic expression of effector genes: Lessons learned and future directions

Henning Gram Hansen; Nusa Pristovsek; Helene Faustrup Kildegaard; Gyun Min Lee

doi:10.1016/j.biotechadv.2016.11.008

Improving the secretory capacity of Chinese hamster ovary cells by ectopic expression of effector genes: Lessons learned and future directions

Henning Gram Hansen, Nusa Pristovsek, Helene Faustrup Kildegaard, Gyun Min Lee

Novo Nordisk Foundation Center for Biosustainability

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Abstract

Chinese hamster ovary (CHO) cells are the preferred cell factory for the production of therapeutic glycoproteins. Although efforts primarily within bioprocess optimization have led to increased product titers of recombinant proteins (r-proteins) expressed in CHO cells, post-transcriptional bottlenecks in the biosynthetic pathway of r-proteins remain to be solved. To this end, the ectopic expression of transgenes (effector genes) offers great engineering potential. However, studies on effector genes have in some cases led to inconsistent results. Whereas this can in part be attributed to product specificity, other experimental and cellular factors are likely important contributors to these conflicting results. Here, these factors are reviewed and discussed with the objective of guiding future studies on effector genes.

Original language	English
Journal	Biotechnology Advances
Volume	35
Issue number	1
Pages (from-to)	64–76
Number of pages	35
ISSN	0734-9750
DOIs	https://doi.org/10.1016/j.biotechadv.2016.11.008
Publication status	Published - 2017

Keywords

Cell engineering
Chinese hamster ovary (CHO) cells
ER stress
Ectopic expression
Endoplasmic reticulum
Gene dosage
Product quality
Recombinant protein production
Secretion bottleneck
Specific productivity

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10.1016/j.biotechadv.2016.11.008

Improving the secretory capacity 222Accepted author manuscript, 466 KBLicence: CC BY-NC-ND

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eCHO Systems: Enhancing CHO by Mammalian Systems Biotechnology
Andersen, M. R. (Project Coordinator), Kildegaard, H. F. (Project Manager), Pristovsek, N. (PhD Student), Domingues Pereira, S. I. (PhD Student), Amann, T. (PhD Student), Singh, A. (PhD Student) & Lohmann, R. (Contact Person)
Horizon 2020 Framework Programme
01/01/2015 → 31/12/2018
Project: Research

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title = "Improving the secretory capacity of Chinese hamster ovary cells by ectopic expression of effector genes: Lessons learned and future directions",

abstract = "Chinese hamster ovary (CHO) cells are the preferred cell factory for the production of therapeutic glycoproteins. Although efforts primarily within bioprocess optimization have led to increased product titers of recombinant proteins (r-proteins) expressed in CHO cells, post-transcriptional bottlenecks in the biosynthetic pathway of r-proteins remain to be solved. To this end, the ectopic expression of transgenes (effector genes) offers great engineering potential. However, studies on effector genes have in some cases led to inconsistent results. Whereas this can in part be attributed to product specificity, other experimental and cellular factors are likely important contributors to these conflicting results. Here, these factors are reviewed and discussed with the objective of guiding future studies on effector genes.",

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Improving the secretory capacity of Chinese hamster ovary cells by ectopic expression of effector genes: Lessons learned and future directions. / Hansen, Henning Gram; Pristovsek, Nusa; Kildegaard, Helene Faustrup et al.
In: Biotechnology Advances, Vol. 35, No. 1, 2017, p. 64–76.

Research output: Contribution to journal › Journal article › Research › peer-review

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T1 - Improving the secretory capacity of Chinese hamster ovary cells by ectopic expression of effector genes: Lessons learned and future directions

AU - Hansen, Henning Gram

AU - Pristovsek, Nusa

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AU - Min Lee, Gyun

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Y1 - 2017

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AB - Chinese hamster ovary (CHO) cells are the preferred cell factory for the production of therapeutic glycoproteins. Although efforts primarily within bioprocess optimization have led to increased product titers of recombinant proteins (r-proteins) expressed in CHO cells, post-transcriptional bottlenecks in the biosynthetic pathway of r-proteins remain to be solved. To this end, the ectopic expression of transgenes (effector genes) offers great engineering potential. However, studies on effector genes have in some cases led to inconsistent results. Whereas this can in part be attributed to product specificity, other experimental and cellular factors are likely important contributors to these conflicting results. Here, these factors are reviewed and discussed with the objective of guiding future studies on effector genes.

KW - Cell engineering

KW - Chinese hamster ovary (CHO) cells

KW - ER stress

KW - Ectopic expression

KW - Endoplasmic reticulum

KW - Gene dosage

KW - Product quality

KW - Recombinant protein production

KW - Secretion bottleneck

KW - Specific productivity

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DO - 10.1016/j.biotechadv.2016.11.008

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EP - 76

JO - Biotechnology Advances

JF - Biotechnology Advances

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Improving the secretory capacity of Chinese hamster ovary cells by ectopic expression of effector genes: Lessons learned and future directions

Abstract

Keywords

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Projects

eCHO Systems: Enhancing CHO by Mammalian Systems Biotechnology

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