{
  "abstract": "Chimeric antigen receptor (CAR) T cell (CAR-T) therapies present options for patients diagnosed with certain leukemias. Recent advances of the technology included a method to integrate the CAR into the T cell receptor alpha constant (TRAC) locus to take advantage of the endogenous promoter and regulatory elements for CAR expression. This method used adeno-associated viral (AAV) vectors based on AAV6 to deliver the donor template encoding the CAR construct. Since the original publication, improvements have been made to this targeted CAR integration technique; however, none of those techniques focused on improving the AAV vector used to deliver the therapeutic cargo. The herein presented study developed a novel AAV capsid directed evolution platform that allows for specifically selecting for novel AAV capsid variants that enable more efficient targeted gene editing-mediated CAR construct integration into the TRAC locus in primary T cells. Using this new platform, we selected several novel AAVs that enable more efficient editing in T cells than AAV6. Two novel capsids, AAV-T1 and AAV-T2, were able to mediate 5-fold improvement for on-target knockin, which resulted in 5-fold reduction of the vector dose to produce highly cytolytic T cells against a brain tumor cell line.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": null,
  "arxiv": null,
  "author_total": 16,
  "authors": [
    {
      "name": "Adrian Westhaus"
    },
    {
      "name": "Elena Barba-Sarasua"
    },
    {
      "name": "Yuyan Chen"
    },
    {
      "name": "Kenneth Hsu"
    },
    {
      "name": "Suzanne Scott"
    },
    {
      "name": "Maddison Knight"
    },
    {
      "name": "Florencia Haase"
    },
    {
      "name": "Santiago Mesa Mora"
    },
    {
      "name": "Benjamin Houghton"
    },
    {
      "name": "Ramon Roca-Pinilla"
    },
    {
      "name": "Predrag Kalajdzic"
    },
    {
      "name": "Geraldine O'Neill"
    },
    {
      "name": "Adrian Thrasher"
    },
    {
      "name": "Giorgia Santilli"
    },
    {
      "name": "Leszek Lisowski"
    },
    {
      "name": "Geraldine O’neill"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/7tn9f9m87h02r.bib",
  "cited_by": 10,
  "doi": "10.1016/j.ymthe.2024.12.012",
  "fulltext_url": null,
  "id": "7tn9f9m87h02r",
  "issns": [
    "1525-0016",
    "1525-0024"
  ],
  "landing_url": "https://hal.science/hal-05772056v1",
  "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": "W4405310215",
  "pdf_url": null,
  "pmcid": null,
  "pmid": "39673125",
  "published": "2026-09-30",
  "publisher": "Cell Press",
  "ris": "https://research.draconitic.com/paper/7tn9f9m87h02r.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:44Z",
      "native_id": "hal-05772056",
      "source": "hal",
      "url": "https://hal.science/hal-05772056v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:1311|Virus-based gene therapy research",
      "subfield": "genetics-genomics"
    }
  ],
  "title": "Tailoring capsid-directed evolution technology for improved AAV-mediated CAR-T generation",
  "title_text": "Tailoring capsid-directed evolution technology for improved AAV-mediated CAR-T generation",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:17:44Z",
  "url": "https://research.draconitic.com/paper/7tn9f9m87h02r",
  "venue": "Molecular Therapy",
  "versions": []
}