Evidence map›Paper›PMID 31110306›Full record

ArticleNature chemical biology2019

Small-molecule control of antibody N-glycosylation in engineered mammalian cells.

Michelle M Chang, Leonid Gaidukov, Giyoung Jung, Wen Allen Tseng, John J Scarcelli, Richard Cornell, Jeffrey K Marshall, Jonathan L Lyles, Paul Sakorafas, An-Hsiang Adam Chu and 10 more

Abstract read
PubMed Publisher
In one paragraph

Article in Nature chemical biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.

0numbers the graph read from it
0cells of the map it votes in
35citing papers in PubMed
7.2field-weighted citation impact, top 2% 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

35 citing papers in PubMed, 71 citations in OpenAlex.

  1. Article
  2. Review
  3. Review
  4. Review
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Review
  11. Article
  12. Article
  13. Review
  14. Article
  15. Review
  16. Engineered PROTAC-CID Systems for Mammalian Inducible Gene Regulation.Journal of the American Chemical Society · 2023
    Article
  17. Review
  18. Article
  19. Review
  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

20 authors at 2 institutions in 1 country.

Michelle M ChangDepartment of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.
Leonid GaidukovDepartment of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.
Giyoung JungSynthetic Biology Center, Massachusetts Institute of Technology, Cambridge, MA, USA.
Wen Allen TsengDepartment of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.ORCID http://orcid.org/0000-0002-8244-8022
John J ScarcelliCell Line Development, Biotherapeutics Pharmaceutical Sciences, Pfizer Inc., Andover, MA, USA.
Richard CornellAnalytical Research and Development, Biotherapeutics Pharmaceutical Sciences, Pfizer Inc., Andover, MA, USA.
Jeffrey K MarshallAnalytical Research and Development, Biotherapeutics Pharmaceutical Sciences, Pfizer Inc., Andover, MA, USA.
Jonathan L LylesSynthetic Biology Center, Massachusetts Institute of Technology, Cambridge, MA, USA.
Paul SakorafasAnalytical Research and Development, Biotherapeutics Pharmaceutical Sciences, Pfizer Inc., Andover, MA, USA.
An-Hsiang Adam ChuAnalytical Research and Development, Biotherapeutics Pharmaceutical Sciences, Pfizer Inc., Andover, MA, USA.
Kaffa CoteAnalytical Research and Development, Biotherapeutics Pharmaceutical Sciences, Pfizer Inc., Andover, MA, USA.
Boriana TzvetkovaAnalytical Research and Development, Biotherapeutics Pharmaceutical Sciences, Pfizer Inc., Andover, MA, USA.
Sepideh DolatshahiDepartment of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.
Madhuresh SumitCulture Process Development, Biotherapeutics Pharmaceutical Sciences, Pfizer Inc., Andover, MA, USA.
Bhanu Chandra MulukutlaCulture Process Development, Biotherapeutics Pharmaceutical Sciences, Pfizer Inc., Andover, MA, USA.
Douglas A LauffenburgerDepartment of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.
Bruno FigueroaCulture Process Development, Biotherapeutics Pharmaceutical Sciences, Pfizer Inc., Andover, MA, USA.
Nevin M SummersSynthetic Biology Center, Massachusetts Institute of Technology, Cambridge, MA, USA.
Timothy K LuDepartment of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.
Ron WeissDepartment of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA. rweiss@mit.edu.ORCID http://orcid.org/0000-0003-0396-2443
Massachusetts Institute of Technology · USPfizer (United States) · US

Funding

Engineered Antibody EGFR Antagonist Cancer TherapeuticsR01CA096504 · NCI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI WITTRUP, KARL DANE · 2002 to 2017
$9.7M
NCI NIH HHS R01 CA096504
6 · The paper itself

Abstract

N-linked glycosylation in monoclonal antibodies (mAbs) is crucial for structural and functional properties of mAb therapeutics, including stability, pharmacokinetics, safety and clinical efficacy. The biopharmaceutical industry currently lacks tools to precisely control N-glycosylation levels during mAb production. In this study, we engineered Chinese hamster ovary cells with synthetic genetic circuits to tune N-glycosylation of a stably expressed IgG. We knocked out two key glycosyltransferase genes, α-1,6-fucosyltransferase (FUT8) and β-1,4-galactosyltransferase (β4GALT1), genomically integrated circuits expressing synthetic glycosyltransferase genes under constitutive or inducible promoters and generated antibodies with concurrently desired fucosylation (0-97%) and galactosylation (0-87%) levels. Simultaneous and independent control of FUT8 and β4GALT1 expression was achieved using orthogonal small molecule inducers. Effector function studies confirmed that glycosylation profile changes affected antibody binding to a cell surface receptor. Precise and rational modification of N-glycosylation will allow new recombinant protein therapeutics with tailored in vitro and in vivo effects for various biotechnological and biomedical applications.

Indexed as

Cell EngineeringAnimalsAntibodies, MonoclonalCHO CellsCricetulusGlycosylationSmall Molecule LibrariesAntibodies, MonoclonalSmall Molecule Libraries

Identifiers

PMID31110306
OpenAlexW2945635306

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.