ArticleNature chemical biology2025
Orthogonalized human protease control of secreted signals.
Article in Nature chemical biology, 2025. 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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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
10 citing papers in PubMed.
- Opportunities for artificial intelligence and synthetic biology in designing living drug delivery systems.Advanced drug delivery reviews · 2026Review
- Genetic Code Expanded T Cell for Controllable Immunotherapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- ProNotch converts extracellular protease activity into programmable transcriptional outputs.bioRxiv : the preprint server for biology · 2026Article
- Monitoring in vivo transcription with synthetic serum markers.Nature communications · 2026Article
- In Situ Engineering of Tumor Cells as Self-Sustaining cDC1 Programming Factories for Effective Cancer Immunotherapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Conversion of natural cytokine receptors into orthogonal synthetic biosensors.Nature chemical biology · 2025Article
- Machine-guided dual-objective protein engineering for deimmunization and therapeutic functions.Cell systems · 2025Article
- Leukocyte dynamics inFrontiers in immunology · 2025Article
- Use of regulatory cells for achieving functional tolerance of pig heart xenotransplants in humans: a literature review.Frontiers in immunology · 2025Review
- Perspectives on Synthetic Protein Circuits in Mammalian Cells.Current opinion in biomedical engineering · 2024Article
Corrections and comments
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Authors and funding
7 authors.
Funding
Abstract
Synthetic circuits that regulate protein secretion in human cells could support cell-based therapies by enabling control over local environments. Although protein-level circuits enable such potential clinical applications, featuring orthogonality and compactness, their non-human origin poses a potential immunogenic risk. In this study, we developed Humanized Drug Induced Regulation of Engineered CyTokines (hDIRECT) as a platform to control cytokine activity exclusively using human-derived proteins. We sourced a specific human protease and its FDA-approved inhibitor. We engineered cytokines (IL-2, IL-6 and IL-10) whose activities can be activated and abrogated by proteolytic cleavage. We used species specificity and re-localization strategies to orthogonalize the cytokines and protease from the human context that they would be deployed in. hDIRECT should enable local cytokine activation to support a variety of cell-based therapies, such as muscle regeneration and cancer immunotherapy. Our work offers a proof of concept for the emerging appreciation of humanization in synthetic biology for human health.
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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.