{
  "abstract": "Recombinant adeno-associated virus is a leading viral vector for gene therapy. However, recombinant adeno-associated virus production systems have low titer and content ratio (ratio of genome-containing to total adeno-associated virus capsids), making it difficult to generate the large number of vector genomes required for clinical or commercial use. In contrast, wildtype adeno-associated virus achieves over ten-fold higher titer compared to recombinant adeno-associated virus and a content ratio of over 95% full. Despite the higher productivity of wildtype adeno-associated virus, the mechanisms behind its productivity remain poorly understood. In this study, we developed and characterized a novel wildtype adeno-associated virus production platform in suspension human embryonic kidney cells across varying multiplicities of infection of adeno-associated virus to adenovirus. The impact of cellular viral genome delivery mechanisms and the interplay between adeno-associated virus and its adenoviral helper were investigated by comparing infection-based systems with transfection-based and infection-transfection hybrid systems. Wildtype and hybrid infection systems had remarkably different host cell growth profiles and viral gene expression patterns, and achieved over a log-fold higher titers and 45% higher content ratios, reaching 8.1 × 10¹² vector genomes/mL culture and 72.2% full, compared to recombinant transfection systems (1.63 × 10¹¹ vector genomes/mL and 26.9% full).",
  "abstract_shown": true,
  "affiliations": [
    "Department of Chemical and Biomolecular Engineering, University of Delaware, Newark, Delaware, USA."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 2,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Sofia Alfieri"
    },
    {
      "affs": [
        0
      ],
      "name": "Kelvin H Lee",
      "orcid": "0000-0003-0908-2981"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/fksgm5hc9s66y.bib",
  "cited_by": 0,
  "doi": "10.1002/biot.70331",
  "fulltext_url": "https://europepmc.org/articles/PMC13721888",
  "id": "fksgm5hc9s66y",
  "issns": [
    "1860-6768",
    "1860-7314"
  ],
  "landing_url": "https://europepmc.org/article/MED/42961188",
  "language": "eng",
  "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": [
    [
      "heading",
      "Research Article"
    ],
    [
      "openalex",
      "1311|Virus-based gene therapy research"
    ]
  ],
  "openalex": "W7224819168",
  "pdf_url": "https://europepmc.org/articles/PMC13721888?pdf=render",
  "pmcid": "PMC13721888",
  "pmid": "42961188",
  "published": "2026-10-30",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/fksgm5hc9s66y.ris",
  "sources": [
    {
      "first_seen": "2026-11-01T00:20:50Z",
      "native_id": "MED:42961188",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42961188"
    },
    {
      "first_seen": "2026-11-03T12:22:30Z",
      "native_id": "PMC13721888",
      "source": "pmc",
      "url": "https://doi.org/10.1002/biot.70331"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:1311|Virus-based gene therapy research",
      "subfield": "genetics-genomics"
    }
  ],
  "title": "Comparison of Wildtype and Recombinant Adeno-Associated Virus (AAV) Production Reveals Distinct Productivity and Content Ratio Profiles.",
  "title_text": "Comparison of Wildtype and Recombinant Adeno-Associated Virus (AAV) Production Reveals Distinct Productivity and Content Ratio Profiles.",
  "type": "peer-reviewed",
  "updated_at": "2026-11-03T12:22:30Z",
  "url": "https://research.draconitic.com/paper/fksgm5hc9s66y",
  "venue": "Biotechnology journal",
  "versions": []
}