Evidence map›Paper›PMID 32170810›Full record

ArticleBiotechnology journal2020

Multi-Omics Reveals Impact of Cysteine Feed Concentration and Resulting Redox Imbalance on Cellular Energy Metabolism and Specific Productivity in CHO Cell Bioprocessing.

Amr S Ali, Rachel Chen, Ravali Raju, Rashmi Kshirsagar, Alan Gilbert, Li Zang, Barry L Karger, Alexander R Ivanov

Open access · greenAbstract read
In one paragraph

Article in Biotechnology journal, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
1.5field-weighted citation impact, top 18% 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

9 citing papers in PubMed, 33 citations in OpenAlex.

  1. Review
  2. Article
  3. 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
  4. Review
  5. Review
  6. Article
  7. CDMOs Play a Critical Role in the Biopharmaceutical Ecosystem.Frontiers in bioengineering and biotechnology · 2022
    Review
  8. Article
  9. Proteomic Profiling of IgG1 Producing CHO Cells Using LC/LC-SPS-MSFrontiers in bioengineering and biotechnology · 2021
    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

8 authors at 2 institutions in 2 countries.

Amr S AliCell Culture Development, Biogen Inc., Cambridge, MA, 02142, USA.ORCID https://orcid.org/0000-0002-7585-9413
Rachel ChenAnalytical Development, Biogen Inc., Cambridge, MA, 02142, USA.
Ravali RajuCell Culture Development, Biogen Inc., Cambridge, MA, 02142, USA.
Rashmi KshirsagarCell Culture Development, Biogen Inc., Cambridge, MA, 02142, USA.
Alan GilbertCell Culture Development, Biogen Inc., Cambridge, MA, 02142, USA.
Li ZangAnalytical Development, Biogen Inc., Cambridge, MA, 02142, USA.
Barry L KargerDepartment of Chemistry and Chemical Biology, Barnett Institute of Chemical and Biological Analysis, Northeastern University, Boston, MA, 02115, USA.
Alexander R IvanovDepartment of Chemistry and Chemical Biology, Barnett Institute of Chemical and Biological Analysis, Northeastern University, Boston, MA, 02115, USA.
Biogen (United States) · USNortheastern University · US

Funding

Effect of methodological and biological variability on molecular profiling of extracellular vesicles in cancer detectionR01CA218500 · NCI · NORTHEASTERN UNIVERSITY · PI GHIRAN, IONITA CALIN, IVANOV, ALEXANDER R. · 2018 to 2022
$4.0M
Deep Proteomic Profiling of Rare CellsR01GM120272 · NIGMS · NORTHEASTERN UNIVERSITY · PI IVANOV, ALEXANDER R. · 2016 to 2019
$1.5M
NCI NIH HHS R01 CA218500NIGMS NIH HHS R01 GM120272NIH HHS 1R01GM120272NIH HHS R01CA218500
6 · The paper itself

Abstract

Chinese hamster ovary (CHO) cells are currently the primary host cell lines used in biotherapeutic manufacturing of monoclonal antibodies (mAbs) and other biopharmaceuticals. Cellular energy metabolism and endoplasmic reticulum (ER) stress are known to greatly impact cell growth, viability, and specific productivity of a biotherapeutic; but the molecular mechanisms are not fully understood. The authors previously employed multi-omics profiling to investigate the impact of a reduction in cysteine (Cys) feed concentration in a fed-batch process and found that disruption of the redox balance led to a substantial decline in cell viability and titer. Here, the multi-omics findings are expanded, and the impact redox imbalance has on ER stress, mitochondrial homeostasis, and lipid metabolism is explored. The reduced Cys feed activates the amino acid response (AAR), increases mitochondrial stress, and initiates gluconeogenesis. Multi-omics analysis reveals that together, ER stress and AAR signaling shift the cellular energy metabolism to rely primarily on anaplerotic reactions, consuming amino acids and producing lactate, to maintain energy generation. Furthermore, the pathways are demonstrated in which this shift in metabolism leads to a substantial decline in specific productivity and altered mAb glycosylation. Through this work, meaningful bioprocess markers and targets for genetic engineering are identified.

Indexed as

Computational BiologyCysteineEnergy MetabolismAnimalsCHO CellsCricetinaeCricetulusOxidation-ReductionCysteineChinese hamster ovary bioprocessingendoplasmic reticulum stressenergy metabolismmonoclonal antibodiesmulti-omicsredox

Identifiers

PMID32170810
PMCPMC7880547
OpenAlexW3011518955

What OpenQuestion holds

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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.