{
  "abstract": "Safe, efficient gene delivery throughout the CNS remains a central obstacle to treating genetic diseases of the brain and spinal cord. We describe BI-TfR1 CapX, a human transferrin receptor (TfR1)-binding AAV capsid that, after a low intravenous dose in adult humanized TFRC mice, transduced more than 80% of cortical and spinal neurons and ~60% of cortical astrocytes, with reduced distribution and expression in several peripheral tissues relative to AAV9. Unlike other engineered BBB-crossing capsids, CapX bound the CNS vasculature within minutes and a large fraction of its genomes reached parenchymal nuclei within 24 hours. Delivering a Prnp-targeted epigenetic silencer (Prnp-CHARM), CapX reduced brain Prnp mRNA by over 95% requiring 18-fold fewer vector genomes per brain cell than AAV-PHP.eB for 50% lowering. A CapX delivered dual-vector cytosine base editor installed a protein-truncating PRNP stop codon lowering brain prion protein by 80%. These properties make CapX an attractive vehicle for human CNS gene therapy.",
  "abstract_shown": true,
  "affiliations": [
    "Broad Institute of MIT and Harvard"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 18,
  "authors": [
    {
      "name": "K. Y. Chan"
    },
    {
      "name": "C.-Y. Lin"
    },
    {
      "name": "Q. Huang"
    },
    {
      "name": "S. Pacouret"
    },
    {
      "name": "Q. Zheng"
    },
    {
      "name": "J. W. Harvey"
    },
    {
      "name": "P. P. Brauer"
    },
    {
      "name": "J. Johnston"
    },
    {
      "name": "F. Serack"
    },
    {
      "name": "J. R. Davis"
    },
    {
      "name": "N. G. Kamath"
    },
    {
      "name": "S. Jereb"
    },
    {
      "name": "D. A. Sprague"
    },
    {
      "name": "A. Svanbergsson"
    },
    {
      "name": "M. Boucher"
    },
    {
      "name": "E. V. Minikel"
    },
    {
      "name": "S. M. Vallabh"
    },
    {
      "affs": [
        0
      ],
      "name": "B. E. Deverman"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/4e603854bdaak.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.09.23.753669",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.09.23.753669v1.full",
  "id": "4e603854bdaak",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.09.23.753669v1",
  "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",
      "neuroscience"
    ],
    [
      "openalex",
      "1311|Virus-based gene therapy research"
    ]
  ],
  "openalex": "W7214782231",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.09.23.753669v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-23",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/4e603854bdaak.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:25:13Z",
      "native_id": "10.64898/2026.09.23.753669",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.09.23.753669v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:neuroscience",
      "subfield": "neuroscience"
    }
  ],
  "title": "BI-TfR1 CapX rapidly transits the blood-brain barrier for efficient, low-dose gene delivery throughout the CNS",
  "title_text": "BI-TfR1 CapX rapidly transits the blood-brain barrier for efficient, low-dose gene delivery throughout the CNS",
  "type": "preprint",
  "updated_at": "2026-10-30T12:25:13Z",
  "url": "https://research.draconitic.com/paper/4e603854bdaak",
  "venue": "bioRxiv",
  "versions": []
}