ArticleNature chemical biology2023
Design of cell-type-specific hyperstable IL-4 mimetics via modular de novo scaffolds.
Article in Nature chemical biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
What it found
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Who cites it
10 citing papers in PubMed, 25 citations in OpenAlex.
- Cytokine co-presentation on targeted lipid nanoparticles enhances in vivo T cell engineering.Biomaterials · 2027Article
- M2-associated microglial states in oligodendrocyte regulation and white matter repair in vascular dementia.Journal of translational medicine · 2026Review
- Review
- Protein engineering: status report.Protein engineering, design & selection : PEDS · 2026Review
- Tuning of G-CSFR signaling by de novo-designed agonists.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- High-Throughput De Novo Protein Design Yields Novel Immunomodulatory Agonists.bioRxiv : the preprint server for biology · 2025Article
- In vitro and in vivo evaluation of chemically synthesized, receptor-biased interleukin-4 and photocaged variants.Science advances · 2025Article
- Conditional Activation of Protein Therapeutics by Templated Removal of Peptide Nucleic Acid Masking Groups.Angewandte Chemie (International ed. in English) · 2025Article
- Cytokines in cancer.Cancer cell · 2025Review
- The JAK-STAT pathway: from structural biology to cytokine engineering.Signal transduction and targeted therapy · 2024Review
Corrections and comments
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Authors and funding
25 authors at 8 institutions in 1 country.
Funding
Abstract
The interleukin-4 (IL-4) cytokine plays a critical role in modulating immune homeostasis. Although there is great interest in harnessing this cytokine as a therapeutic in natural or engineered formats, the clinical potential of native IL-4 is limited by its instability and pleiotropic actions. Here, we design IL-4 cytokine mimetics (denoted Neo-4) based on a de novo engineered IL-2 mimetic scaffold and demonstrate that these cytokines can recapitulate physiological functions of IL-4 in cellular and animal models. In contrast with natural IL-4, Neo-4 is hyperstable and signals exclusively through the type I IL-4 receptor complex, providing previously inaccessible insights into differential IL-4 signaling through type I versus type II receptors. Because of their hyperstability, our computationally designed mimetics can directly incorporate into sophisticated biomaterials that require heat processing, such as three-dimensional-printed scaffolds. Neo-4 should be broadly useful for interrogating IL-4 biology, and the design workflow will inform targeted cytokine therapeutic development.
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Registered trials
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.