ArticleeLife2017
Synthekines are surrogate cytokine and growth factor agonists that compel signaling through non-natural receptor dimers.
Article in eLife, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
45 citing papers in PubMed, 69 citations in OpenAlex.
- Mapping and engineering the human cell-cell interactome.Nature biotechnology · 2026Review
- Rewiring STAT signaling from the cell surface with Trikine immunotherapeutics.Science (New York, N.Y.) · 2026Article
- High-Throughput De Novo Protein Design Yields Novel Immunomodulatory Agonists.bioRxiv : the preprint server for biology · 2025Article
- Geometric Tuning of Cytokine Receptor Association Modulates Synthetic Agonist Signaling.bioRxiv : the preprint server for biology · 2025Article
- Structure-Guided Stapling of Dimeric Conformations and Linker Engineering Enhance Thermostability and Fine-Tune Activity of Bispecific VHH Cytokine Agonists.Antibodies (Basel, Switzerland) · 2025Article
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- Human Synthetic Biology and Programmable Gene Regulation Control.Annual review of genomics and human genetics · 2025Review
- Structural studies of the IFNλ4 receptor complex using cryoEM enabled by protein engineering.Nature communications · 2025Article
- Cytokines in cancer.Cancer cell · 2025Review
- A strategy to design protein-based antagonists against type I cytokine receptors.PLoS biology · 2024Article
- Integrating Computational Design and Experimental Approaches for Next-Generation Biologics.Biomolecules · 2024Review
- The JAK-STAT pathway: from structural biology to cytokine engineering.Signal transduction and targeted therapy · 2024Review
- Article
- Noncovalently particle-anchored cytokines with prolonged tumor retention safely elicit potent antitumor immunity.Science advances · 2024Article
- Pharmacokinetics, pharmacodynamics, and toxicity of a PD-1-targeted IL-15 in cynomolgus monkeys.PloS one · 2024Article
- Multivalent, asymmetric IL-2-Fc fusions show enhanced selectivity for regulatory T cells.Science signaling · 2023Article
- Strategies to therapeutically modulate cytokine action.Nature reviews. Drug discovery · 2023Review
- Molecular and cellular factors determining the functional pleiotropy of cytokines.The FEBS journal · 2023Review
- Cytokimera GIL-11 rescued IL-6R deficient mice from partial hepatectomy-induced death by signaling via non-natural gp130:LIFR:IL-11R complexes.Communications biology · 2023Article
- The ins and outs of innate and adaptive type 2 immunity.Immunity · 2023Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Cytokine and growth-factor ligands typically signal through homo- or hetero-dimeric cell surface receptors via Janus Kinase (JAK/TYK), or Receptor Tyrosine Kinase (RTK)-mediated trans-phosphorylation. However, the number of receptor dimer pairings occurring in nature is limited to those driven by natural ligands encoded within our genome. We have engineered synthethic cytokines (synthekines) that drive formation of cytokine receptor dimer pairings that are not formed by endogenous cytokines and that are not found in nature, and which activate distinct signaling programs. We show that a wide range of non-natural cytokine receptor hetero-dimers are competent to elicit a signaling output. We engineered synthekine ligands that assembled IL-2Rβ/IL-4Rα or IL-4Rα/IFNAR2 receptor heterodimers, that do not occur naturally, triggering signaling and functional responses distinct from those activated by the endogenous cytokines IL-2, IL-4, and IFN. Furthermore, hybrid synthekine ligands that dimerized a JAK/STAT cytokine receptor with a receptor tyrosine kinase (RTK) also elicited a signaling response. Synthekines represent a new family of synthetic ligands with pre-defined receptors, but 'orphan' functions, that enable the full combinatorial scope of dimeric signaling receptors encoded within the human genome to be exploited for basic research and drug discovery.
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What OpenQuestion holds
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.