{
  "abstract": "Synthetic circuits that couple transgene expression to endogenous transcription factor (TF) activity enable cellular response to changing functional states. In T cells, antigen stimulation results in dynamic changes of transcription factor expression programs. Harnessing these endogenous TF dynamics for programmable gene control remains an important challenge in engineered T cells. Here, we develop a library of synthetic promoters (SPs) responsive to seven TFs identified through transcriptomic analysis of T-cell activation programs. These promoters couple endogenous TF activity to transcriptional output across a broad dynamic range of inducibility and basal expression. We quantitatively profile promoter performance in HEK293 and Jurkat cells, evaluate them for orthogonality, and integrate them into Boolean logic gate architectures and network topologies to minimize basal transcriptional leakiness and improve ON/OFF ratios. We test selected synthetic promoters in primary human CD8⁺ T cells, under endogenous TF regulation, and we further characterize the NR4A2-responsive promoter subset in vitro and in tumor-infiltrating engineered T cells in a melanoma xenograft model, demonstrating dynamic and reversible activation.Together, these results provide a modular SP toolkit of TF-responsive synthetic promoters for programmable transcriptional control in engineered T cells.",
  "abstract_shown": true,
  "affiliations": [
    "Center for Advanced Biomaterials for Healthcare, Istituto Italiano di Tecnologia - IIT, Naples, Italy.",
    "Department of Electrical Engineering and Information Technology (DIETI), University of Naples Federico II, Naples, Italy.",
    "Division of Functional Immune Cell Modulation, Leibniz Institute for Immunotherapy, Regensburg, Germany.",
    "Synthetic Biology Center, Department of Biological Engineering, Massachusetts Institute of Technology - MIT, Cambridge, MA, USA.",
    "Medical Clinic and Polyclinic III, Internal Medicine with a focus on Oncology, Hematology and Rheumatology, University Hospital Bonn, Bonn, Germany.",
    "Institute for Bioengineering, School of Engineering, The University of Edinburgh, Edinburgh, UK.",
    "University of Regensburg, Regensburg, Germany.",
    "Center for Advanced Biomaterials for Healthcare, Istituto Italiano di Tecnologia - IIT, Naples, Italy. velia.siciliano@iit.it."
  ],
  "article_type": "research support, non u.s. gov't",
  "arxiv": null,
  "author_total": 20,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Giuliano Bonfá",
      "orcid": "0000-0003-2257-5502"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Giovanna Martino",
      "orcid": "0009-0008-6928-6648"
    },
    {
      "affs": [
        0
      ],
      "name": "Assunta Sellitto"
    },
    {
      "affs": [
        0
      ],
      "name": "Juan Luis Blazquez-Roman"
    },
    {
      "affs": [
        0
      ],
      "name": "Fabiana Tedeschi"
    },
    {
      "affs": [
        0
      ],
      "name": "Antonio Rinaldi"
    },
    {
      "affs": [
        2
      ],
      "name": "Caio Raony Farina Silveira",
      "orcid": "0000-0001-5778-7789"
    },
    {
      "affs": [
        0
      ],
      "name": "Francesca Piro",
      "orcid": "0009-0009-7865-2037"
    },
    {
      "affs": [
        3
      ],
      "name": "Fabio Caliendo"
    },
    {
      "affs": [
        0
      ],
      "name": "Loris Melchiorri"
    },
    {
      "affs": [
        0
      ],
      "name": "Daniela Perna"
    },
    {
      "affs": [
        0
      ],
      "name": "Rita Tarnai"
    },
    {
      "affs": [
        2,
        4
      ],
      "name": "Christoph Heuser-Loy",
      "orcid": "0000-0003-1410-7573"
    },
    {
      "affs": [
        2
      ],
      "name": "Fabio Mastrogiovanni"
    },
    {
      "affs": [
        2
      ],
      "name": "Timea Vadász",
      "orcid": "0000-0001-8570-7125"
    },
    {
      "affs": [
        5
      ],
      "name": "Freddie Starkey"
    },
    {
      "affs": [
        5
      ],
      "name": "Evangelos Nikolados"
    },
    {
      "affs": [
        5
      ],
      "name": "Filippo Menolascina",
      "orcid": "0000-0002-4937-7912"
    },
    {
      "affs": [
        2,
        6
      ],
      "name": "Luca Gattinoni",
      "orcid": "0000-0003-2239-3282"
    },
    {
      "affs": [
        7
      ],
      "name": "Velia Siciliano",
      "orcid": "0000-0001-7734-9153"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/7phhttvcz7xyh.bib",
  "cited_by": 1,
  "doi": "10.1038/s41467-026-77730-7",
  "fulltext_url": "https://europepmc.org/articles/PMC13677741",
  "id": "7phhttvcz7xyh",
  "issns": [
    "2041-1723"
  ],
  "landing_url": "https://europepmc.org/article/MED/42893974",
  "language": "eng",
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "1312|Gene Regulatory Network Analysis"
    ]
  ],
  "openalex": "W7213331118",
  "pdf_url": "https://europepmc.org/articles/PMC13677741?pdf=render",
  "pmcid": "PMC13677741",
  "pmid": "42893974",
  "published": "2026-09-16",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/7phhttvcz7xyh.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:41Z",
      "native_id": "MED:42893974",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42893974"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|Gene Regulatory Network Analysis",
      "subfield": "molecular-biology"
    }
  ],
  "title": "A modular synthetic promoter toolkit for programmable gene control in activated and chronically stimulated T cells.",
  "title_text": "A modular synthetic promoter toolkit for programmable gene control in activated and chronically stimulated T cells.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:19:41Z",
  "url": "https://research.draconitic.com/paper/7phhttvcz7xyh",
  "venue": "Nature communications",
  "versions": []
}