{
  "abstract": "Viral vectors based on recombinant adeno-associated virus (rAAV) have become the most widely used system for therapeutic gene delivery in the central nervous system (CNS). Despite clinical safety and efficacy in neurological applications, a barrier to adoption of the current generation of vectors lies in their limited efficiency, resulting in limited transduction of CNS target cells. To address this limitation, researchers have bioengineered fit-for-purpose AAVs with improved CNS tropism and tissue penetration. While the preclinical assessment of these novel AAVs is primarily conducted in animal models, human induced pluripotent stem cell (hiPSC)-derived organoids offer a unique opportunity to functionally evaluate novel AAV variants in a human context. In this study, we performed a comprehensive and unbiased evaluation of a large number of wild-type and bioengineered AAV capsids for their transduction efficiency in hiPSC-derived brain organoids. We demonstrate that efficient AAV transduction observed in organoids was recapitulated in vivo in both mouse and non-human primate models after cerebrospinal fluid (CSF) delivery. In summary, our study showcases the use of brain organoid systems for the pre-screening of novel AAV vectors. Additionally, we report data for novel AAV variants that exhibit improved CNS transduction efficiency when delivered via the CSF in in vivo preclinical models.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": null,
  "arxiv": null,
  "author_total": 16,
  "authors": [
    {
      "name": "Matthieu Drouyer"
    },
    {
      "name": "Jessica Merjane"
    },
    {
      "name": "Teodora Nedelkoska"
    },
    {
      "name": "Adrian Westhaus"
    },
    {
      "name": "Suzanne Scott"
    },
    {
      "name": "Scott Lee"
    },
    {
      "name": "Peter Burke"
    },
    {
      "name": "Simon Mcmullan"
    },
    {
      "name": "Jose Lanciego"
    },
    {
      "name": "Ana Vicente"
    },
    {
      "name": "Ricardo Bugallo"
    },
    {
      "name": "Carmen Unzu"
    },
    {
      "name": "Gloria González-Aseguinolaza"
    },
    {
      "name": "Anai Gonzalez-Cordero"
    },
    {
      "name": "Leszek Lisowski"
    },
    {
      "name": "Peter G.R. Burke"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/fk6amyzth8npm.bib",
  "cited_by": 27,
  "doi": "10.1016/j.omtn.2024.102264",
  "fulltext_url": null,
  "id": "fk6amyzth8npm",
  "issns": [
    "2162-2531"
  ],
  "landing_url": "https://hal.science/hal-05772044v1",
  "language": "en",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "hal",
      "0.sdv"
    ],
    [
      "openalex",
      "1311|Virus-based gene therapy research"
    ]
  ],
  "openalex": "W4400132914",
  "pdf_url": null,
  "pmcid": null,
  "pmid": "39108635",
  "published": "2026-09-30",
  "publisher": "Elsevier",
  "ris": "https://research.draconitic.com/paper/fk6amyzth8npm.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:44Z",
      "native_id": "hal-05772044",
      "source": "hal",
      "url": "https://hal.science/hal-05772044v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:1311|Virus-based gene therapy research",
      "subfield": "genetics-genomics"
    }
  ],
  "title": "Enhanced AAV transduction across preclinical CNS models: A comparative study in human brain organoids with cross-species evaluations",
  "title_text": "Enhanced AAV transduction across preclinical CNS models: A comparative study in human brain organoids with cross-species evaluations",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:17:44Z",
  "url": "https://research.draconitic.com/paper/fk6amyzth8npm",
  "venue": "Molecular Therapy - Nucleic Acids",
  "versions": []
}