Evidence map›Paper›PMID 38936360›Full record

ArticleCell2024

Preclinical proof of principle for orally delivered Th17 antagonist miniproteins.

Stephanie Berger, Franziska Seeger, Ta-Yi Yu, Merve Aydin, Huilin Yang, Daniel Rosenblum, Laure Guenin-Macé, Caleb Glassman, Lauren Arguinchona, Catherine Sniezek and 16 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.

0numbers the graph read from it
0cells of the map it votes in
44citing papers in PubMed
–field-weighted citation impact
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

44 citing papers in PubMed.

  1. Discovery of a Reversible Sub-Picomolar Thrombin Inhibitor Using DCC.Angewandte Chemie (International ed. in English) · 2026
    Article
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  3. Scalable Production of aPharmaceutics · 2026
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  4. Review
  5. Article
  6. Materials today. Bio · 2026
    Article
  7. Article
  8. Review
  9. Review
  10. Orally available designed miniproteins inhibit enterotoxigenicbioRxiv : the preprint server for biology · 2026
    Article
  11. AI-validated fusion proteins for local inhibition of interleukin-17A.Journal of controlled release : official journal of the Controlled Release Society · 2026
    Article
  12. Protein design and RNA design: Perspectives.Quantitative biology (Beijing, China) · 2026
    Article
  13. Nutrients · 2026
    Article
  14. Article
  15. Computational design of an ultrapotent deltacoronavirus miniprotein inhibitor.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  16. Review
  17. Review
  18. Generalizable Direct Protein Sequencing With InstaNexus.Molecular & cellular proteomics : MCP · 2026
    Article
  19. Review
  20. Miniprotein inhibitors of thebioRxiv : the preprint server for biology · 2026
    Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

26 authors.

Stephanie BergerDepartment of Biochemistry, University of Washington, Seattle, WA 98195, USA; Institute for Protein Design, University of Washington, Seattle, WA 98195, USA. Electronic address: berger389@gmail.com.
Franziska SeegerDepartment of Biochemistry, University of Washington, Seattle, WA 98195, USA; Institute for Protein Design, University of Washington, Seattle, WA 98195, USA.
Ta-Yi YuDepartment of Biochemistry, University of Washington, Seattle, WA 98195, USA; Institute for Protein Design, University of Washington, Seattle, WA 98195, USA; Department of Bioengineering, University of Washington, Seattle, WA 98195, USA.
Merve AydinDepartment of General, Visceral and Transplantation Surgery, LMU University Hospital, LMU Munich, 81377 Munich, Germany.
Huilin YangDepartment of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD 21218, USA; Translational Tissue Engineering Center, Johns Hopkins University, Baltimore, MD 21231, USA.
Daniel RosenblumDepartment of Pathology, NYU Langone Health, New York, NY 10016, USA.
Laure Guenin-MacéDepartment of Pathology, NYU Langone Health, New York, NY 10016, USA; Immunobiology and Therapy Unit, INSERM U1224, Institut Pasteur, Paris 75015, France.
Caleb GlassmanDepartment of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA 94304, USA.
Lauren ArguinchonaDepartment of Biochemistry, University of Washington, Seattle, WA 98195, USA; Institute for Protein Design, University of Washington, Seattle, WA 98195, USA.
Catherine SniezekInstitute for Protein Design, University of Washington, Seattle, WA 98195, USA.
Alyssa BlackstoneInstitute for Protein Design, University of Washington, Seattle, WA 98195, USA.
Lauren CarterInstitute for Protein Design, University of Washington, Seattle, WA 98195, USA.
Rashmi RavichandranInstitute for Protein Design, University of Washington, Seattle, WA 98195, USA.
Maggie AhlrichsInstitute for Protein Design, University of Washington, Seattle, WA 98195, USA.
Michael MurphyInstitute for Protein Design, University of Washington, Seattle, WA 98195, USA.
Ingrid Swanson PultzInstitute for Protein Design, University of Washington, Seattle, WA 98195, USA.
Alex KangDepartment of Biochemistry, University of Washington, Seattle, WA 98195, USA; Institute for Protein Design, University of Washington, Seattle, WA 98195, USA.
Asim K BeraDepartment of Biochemistry, University of Washington, Seattle, WA 98195, USA; Institute for Protein Design, University of Washington, Seattle, WA 98195, USA.
Lance StewartInstitute for Protein Design, University of Washington, Seattle, WA 98195, USA.
K Christopher GarciaDepartment of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA 94304, USA; Department of Structural Biology, Stanford University School of Medicine, Stanford, CA 94304, USA; Howard Hughes Medical Institute, Stanford School of Medicine, Stanford, CA 94305, USA.
Shruti NaikDepartment of Pathology, NYU Langone Health, New York, NY 10016, USA; Department of Medicine, Ronald O. Perelman Department of Dermatology, Perlmutter Cancer Center, NYU Langone Health, New York, NY 10016, USA.
Jamie B SpanglerDepartment of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD 21218, USA; Translational Tissue Engineering Center, Johns Hopkins University, Baltimore, MD 21231, USA; Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD 21218, USA.
Florian BeigelDepartment of Medicine II, LMU University Hospital, LMU Munich, 80336 Munich, Germany.
Matthias SiebeckDepartment of General, Visceral and Transplantation Surgery, LMU University Hospital, LMU Munich, 81377 Munich, Germany.
Roswitha GroppDepartment of General, Visceral and Transplantation Surgery, LMU University Hospital, LMU Munich, 81377 Munich, Germany.
David BakerDepartment of Biochemistry, University of Washington, Seattle, WA 98195, USA; Institute for Protein Design, University of Washington, Seattle, WA 98195, USA; Howard Hughes Medical Institute, University of Washington, Seattle, WA 98195, USA. Electronic address: dabaker@uw.edu.

Funding

Vaccine FacilityP30CA016087 · NCI · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI MARK Reid PHILIPS · 1985 to 2026
$83.1M
User Training and OutreachP30GM124165 · NIGMS · CORNELL UNIVERSITY · PI STEVEN E EALICK · 2018 to 2026
$34.2M
Mechanisms of immune-epithelial crosstalk in tissue repairR01AI168462 · NIAID · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI Shruti Naik · 2022 to 2026
$3.1M
NCI NIH HHS P30 CA016087NIAID NIH HHS R01 AI168462NIGMS NIH HHS P30 GM124165
6 · The paper itself

Abstract

Interleukin (IL)-23 and IL-17 are well-validated therapeutic targets in autoinflammatory diseases. Antibodies targeting IL-23 and IL-17 have shown clinical efficacy but are limited by high costs, safety risks, lack of sustained efficacy, and poor patient convenience as they require parenteral administration. Here, we present designed miniproteins inhibiting IL-23R and IL-17 with antibody-like, low picomolar affinities at a fraction of the molecular size. The minibinders potently block cell signaling in vitro and are extremely stable, enabling oral administration and low-cost manufacturing. The orally administered IL-23R minibinder shows efficacy better than a clinical anti-IL-23 antibody in mouse colitis and has a favorable pharmacokinetics (PK) and biodistribution profile in rats. This work demonstrates that orally administered de novo-designed minibinders can reach a therapeutic target past the gut epithelial barrier. With high potency, gut stability, and straightforward manufacturability, de novo-designed minibinders are a promising modality for oral biologics.

Indexed as

ColitisInterleukin-17Th17 CellsAdministration, OralAnimalsFemaleHumansInterleukin-23MaleMiceMice, Inbred C57BLRatsRats, Sprague-DawleyReceptors, InterleukinTissue DistributionInterleukin-17Interleukin-23Receptors, Interleukinautoinflammationcomputational protein designIL-17IL-23Rinflammatory bowel diseaseoral biologicsprotein engineeringTh17

Identifiers

PMID38936360
PMCPMC11316638

What OpenQuestion holds

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Registered trials

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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.