Evidence map›Paper›PMID 35180317›Full record

ArticleBiotechnology and bioengineering2022

Modeling apoptosis resistance in CHO cells with CRISPR-mediated knockouts of Bak1, Bax, and Bok.

Michael A MacDonald, Craig Barry, Teddy Groves, Verónica S Martínez, Peter P Gray, Kym Baker, Evan Shave, Stephen Mahler, Trent Munro, Esteban Marcellin and 1 more

Open access · hybridAbstract read
In one paragraph

Article in Biotechnology and bioengineering, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
2.4field-weighted citation impact, top 10% 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

15 citing papers in PubMed, 31 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Impact of Dietary Supplementation withAnimals : an open access journal from MDPI · 2025
    Article
  6. Article
  7. Article
  8. Article
  9. Review
  10. Antiapoptosis Engineering for Improved Protein Production from CHO Cells.Methods in molecular biology (Clifton, N.J.) · 2025
    Article
  11. CRISPR Technologies in Chinese Hamster Ovary Cell Line Engineering.International journal of molecular sciences · 2023
    Review
  12. Bok: real killer or bystander with non-apoptotic roles?Frontiers in cell and developmental biology · 2023
    Review
  13. Life at the periphery: what makes CHO cells survival talents.Applied microbiology and biotechnology · 2022
    Article
  14. Article
  15. 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

11 authors at 3 institutions in 3 countries.

Michael A MacDonaldARC Training Centre for Biopharmaceutical Innovation, Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, St. Lucia, Australia.
Craig BarryARC Training Centre for Biopharmaceutical Innovation, Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, St. Lucia, Australia.ORCID 0000-0001-8964-8118
Teddy GrovesThe Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Kgs. Lyngby, Denmark.
Verónica S MartínezARC Training Centre for Biopharmaceutical Innovation, Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, St. Lucia, Australia.ORCID 0000-0003-2729-5278
Peter P GrayARC Training Centre for Biopharmaceutical Innovation, Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, St. Lucia, Australia.
Kym BakerPatheon by Thermo Fisher Scientific, Woolloongabba, Queensland, Australia.
Evan ShavePatheon by Thermo Fisher Scientific, Woolloongabba, Queensland, Australia.
Stephen MahlerARC Training Centre for Biopharmaceutical Innovation, Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, St. Lucia, Australia.
Trent MunroARC Training Centre for Biopharmaceutical Innovation, Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, St. Lucia, Australia.
Esteban MarcellinARC Training Centre for Biopharmaceutical Innovation, Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, St. Lucia, Australia.
Lars K NielsenARC Training Centre for Biopharmaceutical Innovation, Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, St. Lucia, Australia.ORCID 0000-0001-8191-3511
Australian Research Council · AUThermo Fisher Scientific (Israel) · ILNovo Nordisk Foundation · DK

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Chinese hamster ovary (CHO) cells are the primary platform for the production of biopharmaceuticals. To increase yields, many CHO cell lines have been genetically engineered to resist cell death. However, the kinetics that governs cell fate in bioreactors are confounded by many variables associated with batch processes. Here, we used CRISPR-Cas9 to create combinatorial knockouts of the three known BCL-2 family effector proteins: Bak1, Bax, and Bok. To assess the response to apoptotic stimuli, cell lines were cultured in the presence of four cytotoxic compounds with different mechanisms of action. A population-based model was developed to describe the behavior of the resulting viable cell dynamics as a function of genotype and treatment. Our results validated the synergistic antiapoptotic nature of Bak1 and Bax, while the deletion of Bok had no significant impact. Importantly, the uniform application of apoptotic stresses permitted direct observation and quantification of a delay in the onset of cell death through Bayesian inference of meaningful model parameters. In addition to the classical death rate, a delay function was found to be essential in the accurate modeling of the cell death response. These findings represent an important bridge between cell line engineering strategies and biological modeling in a bioprocess context.

Indexed as

ApoptosisProto-Oncogene Proteins c-bcl-2AnimalsBayes Theorembcl-2-Associated X ProteinCHO CellsCricetinaeCricetulusbcl-2-Associated X ProteinProto-Oncogene Proteins c-bcl-2apoptosisBayesian inferencebioprocessingCHO cellsCRISPRpopulation model

Identifiers

PMID35180317
PMCPMC9310834
OpenAlexW4213332269

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.