Evidence map›Paper›PMID 37537499›Full record

ArticleNature biotechnology2024

Design of a mucin-selective protease for targeted degradation of cancer-associated mucins.

Kayvon Pedram, D Judy Shon, Gabrielle S Tender, Natalia R Mantuano, Jason J Northey, Kevin J Metcalf, Simon P Wisnovsky, Nicholas M Riley, Giovanni C Forcina, Stacy A Malaker and 9 more

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature biotechnology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.

0numbers the graph read from it
0cells of the map it votes in
53citing papers in PubMed
12.3field-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

53 citing papers in PubMed, 84 citations in OpenAlex.

  1. Discovery of a secretedGut microbes · 2026
    Article
  2. Review
  3. Engineering CAR-T cells to remodel the mucin-rich cancer cell glycocalyx.bioRxiv : the preprint server for biology · 2026
    Article
  4. Article
  5. Review
  6. Article
  7. Article
  8. Review
  9. Article
  10. Article
  11. Article
  12. Review
  13. Article
  14. The protease cathepsin K can debulk the cancer glycocalyx.The Journal of biological chemistry · 2026
    Article
  15. Article
  16. Article
  17. Article
  18. Review
  19. Mucinase fromFrontiers in microbiology · 2026
    Article
  20. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

19 authors at 8 institutions in 3 countries.

Kayvon Pedram *Department of Chemistry and Sarafan ChEM-H, Stanford University, Stanford, CA, USA.ORCID http://orcid.org/0000-0001-8365-1826
D Judy Shon *Department of Chemistry and Sarafan ChEM-H, Stanford University, Stanford, CA, USA.
Gabrielle S Tender *Department of Chemistry and Sarafan ChEM-H, Stanford University, Stanford, CA, USA.ORCID http://orcid.org/0000-0002-3958-079X
Natalia R MantuanoCancer Immunotherapy Laboratory, Department of Biomedicine, University of Basel, Basel, Switzerland.
Jason J NortheyCenter for Bioengineering and Tissue Regeneration, Department of Surgery, University of California, San Francisco (UCSF), San Francisco, CA, USA.
Kevin J MetcalfCenter for Bioengineering and Tissue Regeneration, Department of Surgery, University of California, San Francisco (UCSF), San Francisco, CA, USA.
Simon P WisnovskyDepartment of Chemistry and Sarafan ChEM-H, Stanford University, Stanford, CA, USA.
Nicholas M RileyDepartment of Chemistry and Sarafan ChEM-H, Stanford University, Stanford, CA, USA.
Giovanni C ForcinaDepartment of Chemistry and Sarafan ChEM-H, Stanford University, Stanford, CA, USA.
Stacy A MalakerDepartment of Chemistry and Sarafan ChEM-H, Stanford University, Stanford, CA, USA.ORCID http://orcid.org/0000-0003-2382-5067
Angel KuoDepartment of Chemistry and Sarafan ChEM-H, Stanford University, Stanford, CA, USA.
Benson M GeorgeInstitute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA, USA.
Caitlyn L MillerDepartment of Chemistry and Sarafan ChEM-H, Stanford University, Stanford, CA, USA.ORCID http://orcid.org/0000-0001-5120-7149
Kerriann M CaseyDepartment of Comparative Medicine, Stanford University, Stanford, CA, USA.ORCID http://orcid.org/0000-0003-4228-928X
José G Vilches-MoureDepartment of Comparative Medicine, Stanford University, Stanford, CA, USA.
Michael J FerracaneDepartment of Chemistry, University of Redlands, Redlands, CA, USA.ORCID http://orcid.org/0000-0002-3007-3126
Valerie M WeaverCenter for Bioengineering and Tissue Regeneration, Department of Surgery, University of California, San Francisco (UCSF), San Francisco, CA, USA.ORCID http://orcid.org/0000-0003-4786-6752
Heinz LäubliCancer Immunotherapy Laboratory, Department of Biomedicine, University of Basel, Basel, Switzerland.
Carolyn R BertozziDepartment of Chemistry and Sarafan ChEM-H, Stanford University, Stanford, CA, USA. bertozzi@stanford.edu.ORCID http://orcid.org/0000-0003-4482-2754
Stanford University · USUniversity of California, San Francisco · USHoward Hughes Medical Institute · USUniversity of Basel · CHBrigham and Women's Hospital · USUniversity of British Columbia · CAUniversity of Redlands · USYale University · US

Funding

Tissue mechanics reprograms the tissue to malignancy and metastasisR35CA242447 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI VALERIE MARIE WEAVER · 2020 to 2026
$6.6M
A physical sciences approach to investigate the role of exosomes in metastatic progressionU01CA250044 · NCI · UNIVERSITY OF PENNSYLVANIA · PI GUO, WEI, RADHAKRISHNAN, RAVI · 2021 to 2025
$3.9M
Targeting the Cancer GlycocalyxR01CA227942 · NCI · STANFORD UNIVERSITY · PI Carolyn Bertozzi · 2019 to 2026
$3.6M
Graduate Training Program in BiotechnologyT32GM141819 · NIGMS · STANFORD UNIVERSITY · PI Eric Andrew Appel, Fan Yang · 2021 to 2026
$1.9M
Uniting Mass Spectrometry and Glycoscience to Investigate Cancer BiologyK00CA212454 · NCI · STANFORD UNIVERSITY · PI RILEY, NICHOLAS M · 2018 to 2021
$331k
Howard Hughes Medical InstituteNCI NIH HHS K00 CA212454NCI NIH HHS R01 CA227942NCI NIH HHS R35 CA242447NCI NIH HHS U01 CA250044NIGMS NIH HHS T32 GM141819
6 · The paper itself

Abstract

Targeted protein degradation is an emerging strategy for the elimination of classically undruggable proteins. Here, to expand the landscape of targetable substrates, we designed degraders that achieve substrate selectivity via recognition of a discrete peptide and glycan motif and achieve cell-type selectivity via antigen-driven cell-surface binding. We applied this approach to mucins, O-glycosylated proteins that drive cancer progression through biophysical and immunological mechanisms. Engineering of a bacterial mucin-selective protease yielded a variant for fusion to a cancer antigen-binding nanobody. The resulting conjugate selectively degraded mucins on cancer cells, promoted cell death in culture models of mucin-driven growth and survival, and reduced tumor growth in mouse models of breast cancer progression. This work establishes a blueprint for the development of biologics that degrade specific protein glycoforms on target cells.

Indexed as

MucinsNeoplasmsAnimalsMicePeptide HydrolasesProteolysisMucinsPeptide Hydrolases

Identifiers

PMID37537499
PMCPMC11018308
OpenAlexW4385555722

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.