Evidence map›Paper›PMID 35301123›Full record

ArticleMetabolic engineering2022

Harnessing secretory pathway differences between HEK293 and CHO to rescue production of difficult to express proteins.

Magdalena Malm, Chih-Chung Kuo, Mona Moradi Barzadd, Aman Mebrahtu, Num Wistbacka, Ronia Razavi, Anna-Luisa Volk, Magnus Lundqvist, David Kotol, Hanna Tegel and 10 more

Open access · hybridAbstract read
In one paragraph

Article in Metabolic engineering, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed, 1 pooled it
3.3field-weighted citation impact, top 7% 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

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

  1. Pooled it
  2. Review
  3. Article
  4. Article
  5. Article
  6. TiOBioprocess and biosystems engineering · 2026
    Article
  7. Article
  8. Article
  9. Cell Engineering for Increasing Production of Recombinant Proteins in Mammalian Cells.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2026
    Review
  10. Article
  11. Review
  12. Reversing transgene silencing via targeted chromatin editing.bioRxiv : the preprint server for biology · 2025
    Article
  13. Article
  14. 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
    Article
  15. Article
  16. Article
  17. Review
  18. Review
  19. Article
  20. Engineering CAR-T Therapeutics for Enhanced Solid Tumor Targeting.Advanced materials (Deerfield Beach, Fla.) · 2025
    Review
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

20 authors at 5 institutions in 3 countries.

Magdalena MalmDept. of Protein Science, KTH - Royal Institute of Technology, Stockholm, SE-106 91, Sweden.
Chih-Chung KuoDepartments of Pediatrics and Bioengineering, University of California, San Diego, La Jolla, CA, 92093, USA; The Novo Nordisk Foundation Center for Biosustainability at the University of California, San Diego, CA, 92093, USA.
Mona Moradi BarzaddDept. of Protein Science, KTH - Royal Institute of Technology, Stockholm, SE-106 91, Sweden.
Aman MebrahtuDept. of Protein Science, KTH - Royal Institute of Technology, Stockholm, SE-106 91, Sweden.
Num WistbackaDept. of Protein Science, KTH - Royal Institute of Technology, Stockholm, SE-106 91, Sweden.
Ronia RazaviDept. of Protein Science, KTH - Royal Institute of Technology, Stockholm, SE-106 91, Sweden.
Anna-Luisa VolkDept. of Protein Science, KTH - Royal Institute of Technology, Stockholm, SE-106 91, Sweden.
Magnus LundqvistDept. of Protein Science, KTH - Royal Institute of Technology, Stockholm, SE-106 91, Sweden.
David KotolScience for Life Laboratory, KTH - Royal Institute of Technology, Solna, 171 65, Sweden.
Hanna TegelDept. of Protein Science, KTH - Royal Institute of Technology, Stockholm, SE-106 91, Sweden.
Sophia HoberDept. of Protein Science, KTH - Royal Institute of Technology, Stockholm, SE-106 91, Sweden.
Fredrik EdforsScience for Life Laboratory, KTH - Royal Institute of Technology, Solna, 171 65, Sweden.
Torbjörn GräslundDept. of Protein Science, KTH - Royal Institute of Technology, Stockholm, SE-106 91, Sweden.
Veronique ChotteauDept. of Industrial Biotechnology, KTH - Royal Institute of Technology, Stockholm, SE-10691, Sweden.
Ray FieldCell Culture and Fermentation Sciences, BioPharmaceutical Development, BioPharmaceuticals R&D, AstraZeneca, Cambridge, UK.
Paul G VarleyCell Culture and Fermentation Sciences, BioPharmaceutical Development, BioPharmaceuticals R&D, AstraZeneca, Cambridge, UK.
Robert G RothDiscovery Biology, Discovery Sciences, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.
Nathan E LewisDepartments of Pediatrics and Bioengineering, University of California, San Diego, La Jolla, CA, 92093, USA; The Novo Nordisk Foundation Center for Biosustainability at the University of California, San Diego, CA, 92093, USA. Electronic address: n4lewis@eng.ucsd.edu.
Diane HattonCell Culture and Fermentation Sciences, BioPharmaceutical Development, BioPharmaceuticals R&D, AstraZeneca, Cambridge, UK.
Johan RockbergDept. of Protein Science, KTH - Royal Institute of Technology, Stockholm, SE-106 91, Sweden. Electronic address: johan.rockberg@biotech.kth.se.
KTH Royal Institute of Technology · SEAstraZeneca (United Kingdom) · GBFoundation Center · USScience for Life Laboratory · SEAstraZeneca (Sweden) · SE

Funding

Unraveling the mammalian secretory pathway through systems biology and algorithm developmentR35GM119850 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI LEWIS, NATHAN ENOCH · 2016 to 2025
$4.3M
NIGMS NIH HHS R35 GM119850
6 · The paper itself

Abstract

Biologics represent the fastest growing group of therapeutics, but many advanced recombinant protein moieties remain difficult to produce. Here, we identify metabolic engineering targets limiting expression of recombinant human proteins through a systems biology analysis of the transcriptomes of CHO and HEK293 during recombinant expression. In an expression comparison of 24 difficult to express proteins, one third of the challenging human proteins displayed improved secretion upon host cell swapping from CHO to HEK293. Guided by a comprehensive transcriptomics comparison between cell lines, especially highlighting differences in secretory pathway utilization, a co-expression screening of 21 secretory pathway components validated ATF4, SRP9, JUN, PDIA3 and HSPA8 as productivity boosters in CHO. Moreover, more heavily glycosylated products benefitted more from the elevated activities of the N- and O-glycosyltransferases found in HEK293. Collectively, our results demonstrate the utilization of HEK293 for expression rescue of human proteins and suggest a methodology for identification of secretory pathway components for metabolic engineering of HEK293 and CHO.

Indexed as

Secretory PathwayAnimalsCHO CellsCricetinaeCricetulusHEK293 CellsHumansRecombinant ProteinsRecombinant ProteinsBioproductionCHODifferential gene expression analysisHEK293Protein secretionSecretory pathwayTranscriptomics

Identifiers

PMID35301123
PMCPMC9189052
OpenAlexW4220848574

What OpenQuestion holds

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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.