{
  "abstract": "Dual-attractor gene networks program distinct states, guiding native cellular decision-making processes such as differentiation. Synthetic dual-attractor circuits (DACs) emulate native gene networks, directing cells to two different states starting from a single, genetically uniform population. However, existing DAC designs for mammalian cells often require multiple genetic cargoes, limiting their application to control cell fate in therapeutically relevant contexts. Here, we leverage model-guided tuning of compact biochemical and biophysical layers of regulation to program two cellular states using a single-cargo DAC. Through activator selection and layering microRNA-mediated mutual repression, we identify and resolve an imbalance between modules that biases states, allowing us to achieve balanced adoption of both states without relying on copy-number variation. Consolidating this optimized DAC into a single cargo, we use gene syntax to minimize bias, generating two balanced states from a single cargo of less than 11 kilobases. Overall, this work establishes design rules for combined biochemical and biophysical tuning of DACs to generate balanced cell states from a single-cargo design, paving the way for programming divergent cell-state trajectories and dual-fate systems.",
  "abstract_shown": true,
  "affiliations": [
    "Massachusetts Institute of Technology"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 6,
  "authors": [
    {
      "name": "E. L. Peterman"
    },
    {
      "name": "N. Nolan"
    },
    {
      "name": "P. M. Naydenkov"
    },
    {
      "name": "D. R. Godavarti"
    },
    {
      "name": "D. Del Vecchio"
    },
    {
      "affs": [
        0
      ],
      "name": "K. E. Galloway"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/267pvvh58v2eb.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.10.19.760260",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.10.19.760260v1.full",
  "id": "267pvvh58v2eb",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.10.19.760260v1",
  "language": null,
  "licence": "CC-BY-NC",
  "licence_label": "CC BY-NC",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "synthetic biology"
    ],
    [
      "openalex",
      "1312|Gene Regulatory Network Analysis"
    ]
  ],
  "openalex": "W7223063978",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.10.19.760260v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-19",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/267pvvh58v2eb.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:28:43Z",
      "native_id": "10.64898/2026.10.19.760260",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.10.19.760260v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:synthetic biology",
      "subfield": "systems-synthetic"
    }
  ],
  "title": "Model-guided design of single-cargo, dual-attractor gene circuits",
  "title_text": "Model-guided design of single-cargo, dual-attractor gene circuits",
  "type": "preprint",
  "updated_at": "2026-10-30T12:28:43Z",
  "url": "https://research.draconitic.com/paper/267pvvh58v2eb",
  "venue": "bioRxiv",
  "versions": []
}