{
  "abstract": "Neural organoids provide tractable models of human brain development, function, and disease, but adeno-associated viral vector (AAV)-based gene delivery is limited by inefficient transduction and insufficient comparative evaluation of the natural and engineered capsids. Here, we evaluated seven AAV capsids (AAV-2, -6, -9, -DJ, -2-retro, -PHP.eB, and -Cap-Mac) for transduction efficiency, cell type tropism, cytotoxicity, and functional integrity in human cortical and thalamic organoids. AAV-Cap-Mac demonstrated the highest transduction efficiency, with broad cellular tropism, but caused cytotoxicity and decreased neuronal activity. By contrast, AAV-DJ yielded efficient neuronal transduction, with preserved calcium dynamics and minimal cytotoxicity, which enabled rabies virus-based circuit tracing and all-optical physiology. Our findings reveal a capsid-dependent trade-off between transduction efficiency and functional integrity and identify AAV-DJ as an optimal serotype for robust gene delivery and physiological interrogation in organoid-based neuroscience. Combining AAV-DJ with emerging molecular and circuit-level technologies in organoids should facilitate mechanistic and translational studies of the human brain.",
  "abstract_shown": true,
  "affiliations": [
    "Laboratory of Cellular Pharmacology, Graduate School of Pharmaceutical Sciences, Nagoya University, Nagoya, Japan",
    "Laboratory of Neural Information Processing, Institute for Advanced Research, Nagoya University, Nagoya, Japan",
    "Research Institute for Quantum and Chemical Innovation, Institutes of Innovation for Future Society, Nagoya University, Nagoya, Japan",
    "iGCORE, Nagoya University, Nagoya, Japan",
    "PRESTO/CREST, Japan Science and Technology Agency, Saitama, Japan"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 6,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Shota Adachi"
    },
    {
      "affs": [
        0
      ],
      "name": "Masatoshi Nishimura"
    },
    {
      "affs": [
        0
      ],
      "name": "Kosuke Yamaguchi"
    },
    {
      "affs": [
        0
      ],
      "name": "Akinori Y. Sato"
    },
    {
      "affs": [
        0
      ],
      "name": "Ryosuke F. Takeuchi"
    },
    {
      "affs": [
        0,
        1,
        2,
        3,
        4
      ],
      "name": "Fumitaka Osakada"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/ac77s6m8m482v.bib",
  "cited_by": 0,
  "doi": "10.1016/j.crmeth.2026.101546",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13721749/",
  "id": "ac77s6m8m482v",
  "issns": [
    "2667-2375"
  ],
  "landing_url": "https://doi.org/10.1016/j.crmeth.2026.101546",
  "language": "en",
  "licence": "CC-BY-NC-ND-4.0",
  "licence_label": "CC BY-NC-ND 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Article"
    ],
    [
      "openalex",
      "1311|Virus-based gene therapy research"
    ]
  ],
  "openalex": "W7202346910",
  "pdf_url": null,
  "pmcid": "PMC13721749",
  "pmid": "42594869",
  "published": "2026-08-13",
  "publisher": "Elsevier",
  "ris": "https://research.draconitic.com/paper/ac77s6m8m482v.ris",
  "sources": [
    {
      "first_seen": "2026-11-03T12:22:23Z",
      "native_id": "PMC13721749",
      "source": "pmc",
      "url": "https://doi.org/10.1016/j.crmeth.2026.101546"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:1311|Virus-based gene therapy research",
      "subfield": "genetics-genomics"
    }
  ],
  "title": "AAV-DJ enables efficient, function-preserving neuronal transduction for circuit interrogation in human cortical and thalamic organoids",
  "title_text": "AAV-DJ enables efficient, function-preserving neuronal transduction for circuit interrogation in human cortical and thalamic organoids",
  "type": "peer-reviewed",
  "updated_at": "2026-11-03T12:22:23Z",
  "url": "https://research.draconitic.com/paper/ac77s6m8m482v",
  "venue": "Cell Reports Methods",
  "versions": []
}