{
  "abstract": "Immunoglobulin G (IgG) is a critical effector of the adaptive immune system, but IgG autoantibodies against self-antigens drive pathology across a wide range of autoimmune diseases. Lowering circulating IgG is a validated and promising therapeutic avenue. Here we developed genetically-encoded lysosome targeting chimeras (GELYTACs) that target circulating IgGs for clearance and degradation. The GELYTACs comprised two protein modules derived from insulin-like growth factor 2 (IGF2) and an IgG-binding nanobody, respectively, and mediated clearance of plasma IgG via the lysosomal trafficking receptor IGF2R. To achieve long-lasting IgG depletion, we encoded GELYTACs in an AAV gene therapy vector and established continuous expression in mice. We also developed conditional GELYACs that are activatable with disease-specific proteases or small molecule drugs and show that GELYTACs can be secreted from cellular therapies. This work establishes GELYTACs as a possible therapeutic modality that is deliverable using genetic medicine approaches.",
  "abstract_shown": true,
  "affiliations": [
    "Stanford University"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 10,
  "authors": [
    {
      "name": "J. L. Yang"
    },
    {
      "name": "K. Y. Loh"
    },
    {
      "name": "C. R. Sandoval Espinoza"
    },
    {
      "name": "D. Schuster"
    },
    {
      "name": "S. A. Yamada-Hunter"
    },
    {
      "name": "L. Labanieh"
    },
    {
      "name": "E. Sotillo"
    },
    {
      "name": "C. Mackall"
    },
    {
      "name": "K. Deisseroth"
    },
    {
      "affs": [
        0
      ],
      "name": "C. Bertozzi"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/bt144kgky86zp.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.07.05.736665",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.07.05.736665v3.full",
  "id": "bt144kgky86zp",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.07.05.736665v3",
  "language": null,
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "synthetic biology"
    ],
    [
      "openalex",
      "1311|Virus-based gene therapy research"
    ]
  ],
  "openalex": "W7167518363",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.07.05.736665v3.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-07-05",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/bt144kgky86zp.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:21:10Z",
      "native_id": "10.64898/2026.07.05.736665",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.07.05.736665v4"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:synthetic biology",
      "subfield": "systems-synthetic"
    }
  ],
  "title": "AAV delivered lysosome-targeting chimeras mediate sustained antibody depletion in vivo",
  "title_text": "AAV delivered lysosome-targeting chimeras mediate sustained antibody depletion in vivo",
  "type": "preprint",
  "updated_at": "2026-11-05T00:21:10Z",
  "url": "https://research.draconitic.com/paper/bt144kgky86zp",
  "venue": "bioRxiv",
  "versions": []
}