{
  "abstract": "Recent clinical successes have intensified interest in using adeno-associated virus (AAV) vectors for therapeutic gene delivery. The liver is a key clinical target, given its critical physiological functions and involvement in a wide range of genetic diseases. Here, we report the bioengineering of a set of next-generation AAV vectors, named AAV-SYDs (where \"SYD\" stands for Sydney, Australia), with increased human hepato-tropism in a liver xenograft mouse model repopulated with primary human hepatocytes. We followed a two-step process that staggered directed evolution and domain-swapping approaches. Using DNA-family shuffling, we first mapped key AAV capsid regions responsible for efficient human hepatocyte transduction in vivo . Focusing on these regions, we next applied domain-swapping strategies to identify and study key capsid residues that enhance primary human hepatocyte uptake and transgene expression. Our findings underscore the potential of AAV-SYDs as liver gene therapy vectors and provide insights into the mechanism responsible for their enhanced transduction profile.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": null,
  "arxiv": null,
  "author_total": 17,
  "authors": [
    {
      "name": "Marti Cabanes-Creus"
    },
    {
      "name": "Renina Gale Navarro"
    },
    {
      "name": "Erhua Zhu"
    },
    {
      "name": "Grober Baltazar"
    },
    {
      "name": "Sophia Liao"
    },
    {
      "name": "Matthieu Drouyer"
    },
    {
      "name": "Anais Amaya"
    },
    {
      "name": "Suzanne Scott"
    },
    {
      "name": "Loan Hanh Nguyen"
    },
    {
      "name": "Adrian Westhaus"
    },
    {
      "name": "Matthias Hebben"
    },
    {
      "name": "Laurence Wilson"
    },
    {
      "name": "Adrian Thrasher"
    },
    {
      "name": "Ian Alexander"
    },
    {
      "name": "Leszek Lisowski"
    },
    {
      "name": "Sophia H.Y. Liao"
    },
    {
      "name": "Laurence O.W. Wilson"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/2h8q61f1cg2tj.bib",
  "cited_by": 44,
  "doi": "10.1016/j.omtm.2021.11.011",
  "fulltext_url": null,
  "id": "2h8q61f1cg2tj",
  "issns": [
    "2329-0501"
  ],
  "landing_url": "https://hal.science/hal-05771983v1",
  "language": "en",
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "hal",
      "0.sdv"
    ],
    [
      "openalex",
      "1311|Virus-based gene therapy research"
    ]
  ],
  "openalex": "W3217126167",
  "pdf_url": null,
  "pmcid": null,
  "pmid": "34977275",
  "published": "2026-09-30",
  "publisher": "Cell Press",
  "ris": "https://research.draconitic.com/paper/2h8q61f1cg2tj.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:44Z",
      "native_id": "hal-05771983",
      "source": "hal",
      "url": "https://hal.science/hal-05771983v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:1311|Virus-based gene therapy research",
      "subfield": "genetics-genomics"
    }
  ],
  "title": "Novel human liver-tropic AAV variants define transferable domains that markedly enhance the human tropism of AAV7 and AAV8",
  "title_text": "Novel human liver-tropic AAV variants define transferable domains that markedly enhance the human tropism of AAV7 and AAV8",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:17:44Z",
  "url": "https://research.draconitic.com/paper/2h8q61f1cg2tj",
  "venue": "Molecular Therapy - Methods and Clinical Development",
  "versions": []
}