Evidence map›Paper›PMID 31140580›Full record

ArticleBiotechnology and bioengineering2019

Comparison of microbial and transient expression (tobacco plants and plant-cell packs) for the production and purification of the anticancer mistletoe lectin viscumin.

Benjamin B Gengenbach, Linda L Keil, Patrick Opdensteinen, Catherine R Müschen, Georg Melmer, Hans Lentzen, Jens Bührmann, Johannes F Buyel

Open access · hybridAbstract readComparative Study
In one paragraph

Article in Biotechnology and bioengineering, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed
2.5field-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

28 citing papers in PubMed, 48 citations in OpenAlex.

  1. Review
  2. Review
  3. Review
  4. Article
  5. Article
  6. The Anti-Inflammatory Activity ofPlants (Basel, Switzerland) · 2023
    Review
  7. Product safety aspects of plant molecular farming.Frontiers in bioengineering and biotechnology · 2023
    Review
  8. Review
  9. Review
  10. Article
  11. Review
  12. Article
  13. Review
  14. Article
  15. Production of active Exendin-4 inFrontiers in plant science · 2022
    Article
  16. Article
  17. Review
  18. Review
  19. Article
  20. Transiently Expressed Mistletoe Lectin II inMolecules (Basel, Switzerland) · 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

8 authors at 4 institutions in 2 countries.

Benjamin B GengenbachIntegrated Production Platforms, Fraunhofer Institute for Molecular Biology and Applied Ecology IME, Aachen, Germany.
Linda L KeilInstitute for Molecular Biotechnology, RWTH Aachen University, Aachen, Germany.
Patrick OpdensteinenIntegrated Production Platforms, Fraunhofer Institute for Molecular Biology and Applied Ecology IME, Aachen, Germany.
Catherine R MüschenIntegrated Production Platforms, Fraunhofer Institute for Molecular Biology and Applied Ecology IME, Aachen, Germany.
Georg MelmerPharmedartis GmbH, Aachen, Germany.
Hans LentzenMELEMA Pharma GmbH, Hamburg, Germany.
Jens BührmannPharmedartis GmbH, Aachen, Germany.
Johannes F BuyelIntegrated Production Platforms, Fraunhofer Institute for Molecular Biology and Applied Ecology IME, Aachen, Germany.ORCID 0000-0003-2361-143X
Fraunhofer Institute for Molecular Biology and Applied Ecology · DEEquilibrium Research · GBFH Aachen · DEAstellas Pharma (Germany) · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Cancer is the leading cause of death in industrialized countries. Cancer therapy often involves monoclonal antibodies or small-molecule drugs, but carbohydrate-binding lectins such as mistletoe (Viscum album) viscumin offer a potential alternative treatment strategy. Viscumin is toxic in mammalian cells, ruling them out as an efficient production system, and it forms inclusion bodies in Escherichia coli such that purification requires complex and lengthy refolding steps. We therefore investigated the transient expression of viscumin in intact Nicotiana benthamiana plants and Nicotiana tabacum Bright Yellow 2 plant-cell packs (PCPs), comparing a full-length viscumin gene construct to separate constructs for the A and B chains. As determined by capillary electrophoresis the maximum yield of purified heterodimeric viscumin in N. benthamiana was ~7 mg/kg fresh biomass with the full-length construct. The yield was about 50% higher in PCPs but reduced 10-fold when coexpressing A and B chains as individual polypeptides. Using a single-step lactosyl-Sepharose affinity resin, we purified viscumin to ~54%. The absence of refolding steps resulted in estimated cost savings of more than 80% when transient expression in tobacco was compared with E. coli. Furthermore, the plant-derived product was ~3-fold more toxic than the bacterially produced counterpart. We conclude that plants offer a suitable alternative for the production of complex biopharmaceutical proteins that are toxic to mammalian cells and that form inclusion bodies in bacteria.

Indexed as

Antineoplastic Agents, PhytogenicEscherichia coliGene ExpressionNicotianaPlant ProteinsPlants, Genetically ModifiedRibosome Inactivating Proteins, Type 2Toxins, BiologicalPlant CellsRecombinant ProteinsAntineoplastic Agents, Phytogenicmistletoe lectin IPlant ProteinsRecombinant ProteinsRibosome Inactivating Proteins, Type 2Toxins, Biologicalcancer therapydesign of experimentsmolecular farmingplant-cell packrecombinant viscumintransient protein expression

Identifiers

PMID31140580
PMCPMC6772165
OpenAlexW2946955272

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.