Evidence map›Paper›PMID 31956982›Full record

ArticleBiotechnology and bioengineering2020

Overexpression of transcription factor Foxa1 and target genes remediate therapeutic protein production bottlenecks in Chinese hamster ovary cells.

Audrey Berger, Valérie Le Fourn, Jacqueline Masternak, Alexandre Regamey, Iris Bodenmann, Pierre-Alain Girod, Nicolas Mermod

Open access · hybridAbstract read
In one paragraph

Article in Biotechnology and bioengineering, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed, 1 pooled it
2.3field-weighted citation impact, top 11% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

24 citing papers in PubMed, 1 synthesis or guideline pooled it, 42 citations in OpenAlex.

  1. Pooled it
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  5. Deciphering the determinants of recombinant protein expression across the human secretome.Proceedings of the National Academy of Sciences of the United States of America · 2025
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  20. Cell culture bioprocessing - the road taken and the path forward.Current opinion in chemical engineering · 2020
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 3 institutions in 1 country.

Audrey BergerDepartment of Fundamental Microbiology, Institute of Biotechnology, University of Lausanne, Lausanne, Switzerland.
Valérie Le FournSelexis SA, Geneva, Switzerland.
Jacqueline MasternakDepartment of Fundamental Microbiology, Institute of Biotechnology, University of Lausanne, Lausanne, Switzerland.
Alexandre RegameySelexis SA, Geneva, Switzerland.
Iris BodenmannSelexis SA, Geneva, Switzerland.
Pierre-Alain GirodSelexis SA, Geneva, Switzerland.
Nicolas MermodDepartment of Fundamental Microbiology, Institute of Biotechnology, University of Lausanne, Lausanne, Switzerland.ORCID 0000-0001-7741-3186
Addex Therapeutics (Switzerland) · CHUniversity of Lausanne · CHÉcole Polytechnique Fédérale de Lausanne · CH

Funding

Kommission für Technologie und Innovation 13939.1 PFLS-LSSelexis SA 13939.1 PFLS-LSUniversité de Lausanne
6 · The paper itself

Abstract

Despite extensive research conducted to increase protein production from Chinese hamster ovary (CHO) cells, cellular bottlenecks often remain, hindering high yields. In this study, a transcriptomic analysis led to the identification of 32 genes that are consistently upregulated in high producer clones and thus might mediate high productivity. Candidate genes were associated with functions such as signaling, protein folding, cytoskeleton organization, and cell survival. We focused on two engineering targets, Erp27, which binds unfolded proteins and the Erp57 disulfide isomerase in the endoplasmic reticulum, and Foxa1, a pioneering transcription factor involved in organ development. Erp27 moderate overexpression increased production of an easy-to-express antibody, whereas Erp27 and Erp57 co-overexpression increased cell density, viability, and the yield of difficult-to-express proteins. Foxa1 overexpression increased cell density, cell viability, and easy- and difficult-to-express protein yields, whereas it decreased reactive oxygen species late in fed-batch cultures. Foxa1 overexpression upregulated two other candidate genes that increased the production of difficult- and/or easy-to-express proteins, namely Ca3, involved in protecting cells from oxidative stress, and Tagap, involved in signaling and cytoskeleton remodeling. Overall, several genes allowing to overcome CHO cell bottlenecks were identified, including Foxa1, which mediated multiple favorable metabolic changes that improve therapeutic protein yields.

Indexed as

Hepatocyte Nuclear Factor 3-alphaRecombinant ProteinsAnimalsCell EngineeringCell SurvivalCHO CellsCricetinaeCricetulusProtein FoldingHepatocyte Nuclear Factor 3-alphaRecombinant Proteinscell viabilityCHO cellsFoxa1 transcription factorprotein foldingrecombinant protein production

Identifiers

PMID31956982
PMCPMC7079004
OpenAlexW3002227902

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.