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

Research output: Contribution to journalJournal articleResearchpeer-review

1791 Downloads (Pure)

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 languageEnglish
JournalBiotechnology Advances
Volume35
Issue number1
Pages (from-to)64–76
Number of pages35
ISSN0734-9750
DOIs
Publication statusPublished - 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

Cite this

@article{d82934141d834cdebd35d5339a98b4f4,
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.",
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",
author = "Hansen, {Henning Gram} and Nusa Pristovsek and Kildegaard, {Helene Faustrup} and {Min Lee}, Gyun",
year = "2017",
doi = "10.1016/j.biotechadv.2016.11.008",
language = "English",
volume = "35",
pages = "64–76",
journal = "Biotechnology Advances",
issn = "0734-9750",
publisher = "Elsevier",
number = "1",

}

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; Min Lee, Gyun.

In: Biotechnology Advances, Vol. 35, No. 1, 2017, p. 64–76.

Research output: Contribution to journalJournal articleResearchpeer-review

TY - JOUR

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

AU - Kildegaard, Helene Faustrup

AU - Min Lee, Gyun

PY - 2017

Y1 - 2017

N2 - 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.

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

U2 - 10.1016/j.biotechadv.2016.11.008

DO - 10.1016/j.biotechadv.2016.11.008

M3 - Journal article

VL - 35

SP - 64

EP - 76

JO - Biotechnology Advances

JF - Biotechnology Advances

SN - 0734-9750

IS - 1

ER -