{
  "abstract": "Chimeric antigen receptor (CAR) intracellular domains (ICDs) couple antigen recognition to T-cell activation. Here we worked with AI agents to refactor CAR ICDs, proposing designs and refining them as measurements accumulated over three rounds. This approach yielded KRGR-{zeta}1-40, a 45-amino-acid ICD less than a third the length of the clinical 4-1BB-CD3{zeta} (BB{zeta}) ICD. Compared with BB{zeta}, KRGR-{zeta}1-40 increased CAR surface expression and antigen-driven IFN-{gamma} release, without detectable antigen-independent IFN-{gamma} release. KRGR-{zeta}1-40 extended CAR expression and target-cell killing after transient mRNA delivery, supported the expression of four CARs from a shared mRNA dose, and enhanced B-cell depletion after lentiviral and lipid-nanoparticle delivery. These results show that iterative agent-guided design with experimental feedback can yield compact ICDs that enhance CAR expression and sustain CAR T-cell function.",
  "abstract_shown": true,
  "affiliations": [
    "Generate Biomedicines"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 9,
  "authors": [
    {
      "name": "L. Bai"
    },
    {
      "name": "A. Kumar"
    },
    {
      "name": "H. J. Desai"
    },
    {
      "name": "J. Li"
    },
    {
      "name": "D. P. de Alwis"
    },
    {
      "name": "D. Hazuda"
    },
    {
      "name": "G. Grigoryan"
    },
    {
      "name": "W. Wang"
    },
    {
      "affs": [
        0
      ],
      "name": "J. Yi"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/6f53pf70y3e7h.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.10.28.762481",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.10.28.762481v1.full",
  "id": "6f53pf70y3e7h",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.10.28.762481v1",
  "language": null,
  "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": [
    [
      "biorxiv",
      "bioengineering"
    ]
  ],
  "openalex": null,
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.10.28.762481v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-28",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/6f53pf70y3e7h.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:30:30Z",
      "native_id": "10.64898/2026.10.28.762481",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.10.28.762481v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:bioengineering",
      "subfield": "systems-synthetic"
    }
  ],
  "title": "Refactored intracellular domains enhance CAR expression and function",
  "title_text": "Refactored intracellular domains enhance CAR expression and function",
  "type": "preprint",
  "updated_at": "2026-10-31T00:20:50Z",
  "url": "https://research.draconitic.com/paper/6f53pf70y3e7h",
  "venue": "bioRxiv",
  "versions": []
}