{
  "abstract": "DNA-PK inhibitors (DNA-PKi) have emerged as potent enhancers of homology-directed repair (HDR) in genome editing, however, recent studies have reported that such inhibitors can induce large-scale structural variations (SVs) raising safety concerns. To investigate factors influencing SV induction in human hematopoietic stem and progenitor cells (HSPCs), we employed a combination of on-target long-read nanopore sequencing and unbiased genome wide detection of SVs using Strand-seq. Our results show that editing alone results in a high frequency of large on-target deletions which were modestly increased by DNA-PK inhibition and could be mitigated using DNA polQ inhibitors. Genome-wide SVs were also induced at low frequencies by editing but were not substantially increased with DNA-PKi. SVs including translocations were, however, increased with multiple simultaneous editing. Our results highlight that edit-induced SVs are not limited to DNA-PKi enhanced protocols, thus careful assessment will be critical to ensure the safety of any edited therapeutic cell product.",
  "abstract_shown": true,
  "affiliations": [
    "Institut de Recherche en Immunologie et Cancerologie, Universite de Montreal, Canada"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 5,
  "authors": [
    {
      "name": "F.-M. Cloarec-Ung"
    },
    {
      "name": "G. Sauvageau"
    },
    {
      "name": "H. M. Sheppard"
    },
    {
      "name": "P. M. Lansdorp"
    },
    {
      "affs": [
        0
      ],
      "name": "D. J. Knapp"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/52tzbyj6tdn5e.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.06.13.732078",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.06.13.732078v2.full",
  "id": "52tzbyj6tdn5e",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.06.13.732078v2",
  "language": null,
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "molecular biology"
    ],
    [
      "openalex",
      "1312|CRISPR and Genetic Engineering"
    ]
  ],
  "openalex": "W7164916202",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.06.13.732078v2.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-06-13",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/52tzbyj6tdn5e.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:22:36Z",
      "native_id": "10.64898/2026.06.13.732078",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.06.13.732078v2"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "biorxiv:molecular biology",
      "subfield": "molecular-biology"
    }
  ],
  "title": "Genome-wide structural variant landscape following HDR-enhanced CRISPR editing in human hematopoietic stem and progenitor cells",
  "title_text": "Genome-wide structural variant landscape following HDR-enhanced CRISPR editing in human hematopoietic stem and progenitor cells",
  "type": "preprint",
  "updated_at": "2026-10-30T12:22:36Z",
  "url": "https://research.draconitic.com/paper/52tzbyj6tdn5e",
  "venue": "bioRxiv",
  "versions": []
}