Evidence map›Paper›PMID 26011187›Full record

ArticlePlant biotechnology journal2016

Multiplexed, targeted gene editing in Nicotiana benthamiana for glyco-engineering and monoclonal antibody production.

Jin Li, Thomas J Stoddard, Zachary L Demorest, Pierre-Olivier Lavoie, Song Luo, Benjamin M Clasen, Frederic Cedrone, Erin E Ray, Andrew P Coffman, Aurelie Daulhac and 6 more

Open access · bronzeAbstract read
In one paragraph

Article in Plant biotechnology journal, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.

0numbers the graph read from it
0cells of the map it votes in
45citing papers in PubMed
10.7field-weighted citation impact, top 1% 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

45 citing papers in PubMed, 104 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Review
  5. Review
  6. Article
  7. Review
  8. Green Biologics: Harnessing the Power of Plants to Produce Pharmaceuticals.International journal of molecular sciences · 2023
    Review
  9. Article
  10. Article
  11. Review
  12. Review
  13. Plant-based biopharmaceutical engineering.Nature reviews bioengineering · 2023
    Review
  14. An oligosaccharyltransferase fromFrontiers in plant science · 2023
    Article
  15. Engineering theFrontiers in plant science · 2022
    Article
  16. Article
  17. Review
  18. Glyco-Engineering of Plant-Based Expression Systems.Advances in biochemical engineering/biotechnology · 2021
    Article
  19. Article
  20. 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

16 authors at 2 institutions in 2 countries.

Jin LiCellectis Plant Sciences Inc., New Brighton, MN, USA.
Thomas J StoddardCellectis Plant Sciences Inc., New Brighton, MN, USA.
Zachary L DemorestCellectis Plant Sciences Inc., New Brighton, MN, USA.
Pierre-Olivier LavoieMedicago Inc., Québec, QC, Canada.
Song LuoCellectis Plant Sciences Inc., New Brighton, MN, USA.
Benjamin M ClasenCellectis Plant Sciences Inc., New Brighton, MN, USA.
Frederic CedroneCellectis SA, Paris, France.
Erin E RayCellectis Plant Sciences Inc., New Brighton, MN, USA.
Andrew P CoffmanCellectis Plant Sciences Inc., New Brighton, MN, USA.
Aurelie DaulhacCellectis Plant Sciences Inc., New Brighton, MN, USA.
Ann YabandithCellectis Plant Sciences Inc., New Brighton, MN, USA.
Adam J RetterathCellectis Plant Sciences Inc., New Brighton, MN, USA.
Luc MathisCellectis Plant Sciences Inc., New Brighton, MN, USA.
Daniel F VoytasCellectis Plant Sciences Inc., New Brighton, MN, USA.
Marc-André D'AoustMedicago Inc., Québec, QC, Canada.
Feng ZhangCellectis Plant Sciences Inc., New Brighton, MN, USA.
Cellectis (United States) · USMedicago (Canada) · CA

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Biopharmaceutical glycoproteins produced in plants carry N-glycans with plant-specific residues core α(1,3)-fucose and β(1,2)-xylose, which can significantly impact the activity, stability and immunogenicity of biopharmaceuticals. In this study, we have employed sequence-specific transcription activator-like effector nucleases (TALENs) to knock out two α(1,3)-fucosyltransferase (FucT) and the two β(1,2)-xylosyltransferase (XylT) genes within Nicotiana benthamiana to generate plants with improved capacity to produce glycoproteins devoid of plant-specific residues. Among plants regenerated from N. benthamiana protoplasts transformed with TALENs targeting either the FucT or XylT genes, 50% (80 of 160) and 73% (94 of 129) had mutations in at least one FucT or XylT allele, respectively. Among plants regenerated from protoplasts transformed with both TALEN pairs, 17% (18 of 105) had mutations in all four gene targets, and 3% (3 of 105) plants had mutations in all eight alleles comprising both gene families; these mutations were transmitted to the next generation. Endogenous proteins expressed in the complete knockout line had N-glycans that lacked β(1,2)-xylose and had a significant reduction in core α(1,3)-fucose levels (40% of wild type). A similar phenotype was observed in the N-glycans of a recombinant rituximab antibody transiently expressed in the homozygous mutant plants. More importantly, the most desirable glycoform, one lacking both core α(1,3)-fucose and β(1,2)-xylose residues, increased in the antibody from 2% when produced in the wild-type line to 55% in the mutant line. These results demonstrate the power of TALENs for multiplexed gene editing. Furthermore, the mutant N. benthamiana lines provide a valuable platform for producing highly potent biopharmaceutical products.

Indexed as

Antibodies, MonoclonalBase SequenceFucoseGene EditingGenetic EngineeringGlycosylationMutationNicotianaPlant ProteinsPlants, Genetically ModifiedPolysaccharidesProtoplastsRituximabTranscription Activator-Like Effector NucleasesTransformation, GeneticXyloseAntibodies, MonoclonalFucosePlant ProteinsPolysaccharidesRituximabTranscription Activator-Like Effector NucleasesXyloseGene editingglyco-engineeringplant-derived pharmaceuticalstranscription activator-like effector nucleases

Identifiers

PMID26011187
PMCPMC11389102
OpenAlexW2104459589

What OpenQuestion holds

Textmetadata
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.