ArticleNature2019
De novo design of potent and selective mimics of IL-2 and IL-15.
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In one paragraph
Article in Nature, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 316 papers, 2 of them syntheses that pooled it.
0numbers the graph read from it
0cells of the map it votes in
316citing papers in PubMed, 2 pooled it
24.7field-weighted citation impact, top 1% of its field
What it found
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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.
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.
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Who cites it
316 citing papers in PubMed, 2 syntheses or guidelines pooled it, 534 citations in OpenAlex.
- A systematic review of interleukin-2-based immunotherapies in clinical trials for cancer and autoimmune diseases.EBioMedicine · 2023Pooled it
- Engineering cytokines for cancer immunotherapy: a systematic review.Frontiers in immunology · 2023Pooled it
- Computational design of metalloproteases.Nature · 2026Article
- αTIGIT-guided IL-15 mimetics drive potent and safe antitumor immunity by restoring tumor-infiltrating T cells.Cellular & molecular immunology · 2026Article
- De novo design of protease-activatable cytokine prodrugs.bioRxiv : the preprint server for biology · 2026Article
- Arming oncolytic Coxsackievirus B3 with Neoleukin-2/15 enhances growth inhibition of colorectal carcinomas and induces T cell activation.Molecular therapy. Oncology · 2026Article
- Messenger RNA delivery of a dual CD25/CD122 affinity-tuned IL-2 variant prolongs exposure and potentiates antitumor T cell immunity.Science advances · 2026Article
- Scalable Production of aPharmaceutics · 2026Article
- Accelerating protein design by scaling experimental characterization.Nature communications · 2026Article
- Applications of synthetic biology in biomedicine.Molecular biomedicine · 2026Review
- Mapping and engineering the human cell-cell interactome.Nature biotechnology · 2026Review
- Total Chemical Synthesis of Interleukin-15 and Interleukin-2: Taming Protein Hydrophobicity and Aggregation by a Versatile Solubilizing Strategy.Angewandte Chemie (International ed. in English) · 2026Article
- Towards Cost-Effective and Sustainable Media Formulations for Terrestrial and Aquatic Cellular Agriculture.Foods (Basel, Switzerland) · 2026Review
- Regulatory T cells sabotage anti-tumor γδ T cells by creating IL-2-deficient environments.The Journal of experimental medicine · 2026Article
- Adaptive resistance in cancer immunotherapy.Cellular & molecular immunology · 2026Review
- Review
- The dual balance of the cytokine network: key messengers of immune activation and triggers of cytokine storm.Biomarker research · 2026Review
- Bridging structure and function: artificial intelligence-based modelling of kidney proteins.Nature reviews. Nephrology · 2026Review
- Rewiring STAT signaling from the cell surface with Trikine immunotherapeutics.Science (New York, N.Y.) · 2026Article
- Covalent tumor anchoring spatially orchestrates antitumor immunity.bioRxiv : the preprint server for biology · 2026Article
256 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
Authors and funding
25 authors at 7 institutions in 4 countries.
Daniel-Adriano Silva *Institute for Protein Design, University of Washington, Seattle, WA, USA. dadriano@uw.edu.
Shawn Yu *Institute for Protein Design, University of Washington, Seattle, WA, USA.
Umut Y Ulge *Institute for Protein Design, University of Washington, Seattle, WA, USA.
Jamie B Spangler *Departments of Biomedical Engineering and Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD, USA.
Kevin M JudeDepartments of Molecular and Cellular Physiology and Structural Biology, Stanford University School of Medicine, Stanford, CA, USA.
Carlos Labão-AlmeidaInstituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal.
Lestat R AliDivision of Gastroenterology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Alfredo Quijano-RubioInstitute for Protein Design, University of Washington, Seattle, WA, USA.
Mikel RuterbuschDepartment of Immunology, University of Washington School of Medicine, Seattle, WA, USA.
Isabel LeungFred Hutchinson Cancer Research Center, Clinical Research Division, Seattle, WA, USA.
Tamara BiaryDivision of Gastroenterology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Stephanie J CrowleyDivision of Gastroenterology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Enrique MarcosInstitute for Protein Design, University of Washington, Seattle, WA, USA.
Carl D WalkeyInstitute for Protein Design, University of Washington, Seattle, WA, USA.
Brian D WeitznerInstitute for Protein Design, University of Washington, Seattle, WA, USA.
Fátima Pardo-AvilaDepartment of Structural Biology, Stanford University School of Medicine, Stanford, CA, USA.
Javier CastellanosInstitute for Protein Design, University of Washington, Seattle, WA, USA.
Lauren CarterInstitute for Protein Design, University of Washington, Seattle, WA, USA.
Lance StewartInstitute for Protein Design, University of Washington, Seattle, WA, USA.
Stanley R RiddellFred Hutchinson Cancer Research Center, Clinical Research Division, Seattle, WA, USA.
Marion PepperDepartment of Immunology, University of Washington School of Medicine, Seattle, WA, USA.
Gonçalo J L BernardesInstituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal.
Michael DouganDivision of Gastroenterology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
K Christopher GarciaDepartments of Molecular and Cellular Physiology and Structural Biology, Stanford University School of Medicine, Stanford, CA, USA. kcgarcia@stanford.edu.
David BakerInstitute for Protein Design, University of Washington, Seattle, WA, USA. dabaker@uw.edu.
University of Washington · USStanford University · USFred Hutch Cancer Center · USHarvard University · USMassachusetts General Hospital · USUniversity of Cambridge · GBUniversity of Lisbon · PT
Funding
X-ray Absorption Spectroscopy (XAS) pp.711-759P41GM103393 · NIGMS · STANFORD UNIVERSITY · PI HODGSON, KEITH O · 2012 to 2019
$30.6MUniversity of Washington Medical Scientist Training Program: MD/PhDT32GM007266 · NIGMS · UNIVERSITY OF WASHINGTON · PI HORWITZ, MARSHALL S. · 1985 to 2023
$30.4MStructure-based engineering of immune cytokine signalingR01AI051321 · NIAID · STANFORD UNIVERSITY · PI Kenan Christopher GARCIA · 2002 to 2026
$5.6MEmergent Properties of Complex Systems: From Atoms to Macromolecules; from Humans to SocietiesR35GM122543 · NIGMS · STANFORD UNIVERSITY · PI MICHAEL LEVITT · 2017 to 2026
$5.1MStructure, function and engineering of immune cytokine receptor signalingR37AI051321 · NIAID · STANFORD UNIVERSITY · PI GARCIA, KENAN CHRISTOPHER · 2013 to 2022
$4.2MThe differentiation and function of CD4+ Th2 cells during allergen-induced asthmaR01AI108626 · NIAID · UNIVERSITY OF WASHINGTON · PI PEPPER, MARION · 2014 to 2018
$2.4MHigh-Speed High-Sensitivity Detector for X-ray Micro-Crystallography at GM/CA@APSS10OD012289 · OD · UNIVERSITY OF CHICAGO · PI FISCHETTI, ROBERT F. · 2014 to 2014
$2.0MProtein-Protein InteractionsR01GM059224 · NIGMS · UNIVERSITY OF WASHINGTON · PI BAKER, DAVID · 1999 to 2009
$1.8MPilatus 6mS10OD021832 · OD · UNIVERSITY OF CALIFORNIA BERKELEY · PI ADAMS, PAUL DAVID · 2016 to 2016
$980kRegulation of brown fat metabolism by the immune receptor PD-L1K08DK114563 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI DOUGAN, MICHAEL LAWRENCE · 2017 to 2021
$868kHoward Hughes Medical InstituteNIAID NIH HHS R01 AI051321NIAID NIH HHS R01 AI108626NIAID NIH HHS R37 AI051321NIDDK NIH HHS K08 DK114563NIGMS NIH HHS P41 GM103393NIGMS NIH HHS R01 GM059224NIGMS NIH HHS R35 GM122543NIGMS NIH HHS T32 GM007266NIH HHS S10 OD012289NIH HHS S10 OD021832
Abstract
We describe a de novo computational approach for designing proteins that recapitulate the binding sites of natural cytokines, but are otherwise unrelated in topology or amino acid sequence. We use this strategy to design mimics of the central immune cytokine interleukin-2 (IL-2) that bind to the IL-2 receptor βγ
Indexed as
Drug DesignMolecular MimicryAmino Acid SequenceAnimalsBinding SitesColonic NeoplasmsComputer SimulationCrystallography, X-RayDisease Models, AnimalHumansInterleukin-15Interleukin-2Interleukin-2 Receptor alpha SubunitMelanomaMiceModels, MolecularInterleukin-15Interleukin-2Interleukin-2 Receptor alpha SubunitReceptors, Interleukin-2
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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.