{
  "abstract": "Selection-marker-assisted homology-directed repair (HDR) efficiently edits coding sequence termini but is poorly suited for internal exons. Here, we developed artificial reporter intron-based HDR (ARI-HDR), which inserts a selectable intron into target exons to enable precise internal-exon editing. Although designed for scarless removal by splicing, ARIs frequently exhibit inaccurate splicing. Using a random mutagenesis reporter assay, we identified intron upstream sequences (IUS) as key determinants of splicing fidelity and screened degenerate IUS variants to obtain reliably spliced ARI donors. ARI-HDR successfully introduced site-specific mutations into five human genes. Combining long single-stranded DNA donors with conversion-tract optimization increased editing efficiency to over 80%. This efficiency enabled 'Dirty-Editing,' a streamlined workflow that generates precisely edited mixed-cell populations without single-cell cloning. Together, ARI-HDR extends selection-based enrichment to internal exons across protein-coding genes, while our splicing-optimized intron design offers a broadly applicable solution for artificial intron-based technologies.",
  "abstract_shown": true,
  "affiliations": [
    "The First Affiliated Hospital, Shenzhen University; Shenzhen Second People's Hospital"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 6,
  "authors": [
    {
      "name": "S. wang"
    },
    {
      "name": "X. Wang"
    },
    {
      "name": "M. Shang"
    },
    {
      "name": "M. Zhang"
    },
    {
      "name": "K. Wu"
    },
    {
      "affs": [
        0
      ],
      "name": "W. Huang"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/3dt757cgqkhgr.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.10.16.759525",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.10.16.759525v1.full",
  "id": "3dt757cgqkhgr",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.10.16.759525v1",
  "language": null,
  "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": [
    [
      "biorxiv",
      "molecular biology"
    ],
    [
      "openalex",
      "1312|CRISPR and Genetic Engineering"
    ]
  ],
  "openalex": "W7222761805",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.10.16.759525v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-16",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/3dt757cgqkhgr.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:28:07Z",
      "native_id": "10.64898/2026.10.16.759525",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.10.16.759525v1"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "biorxiv:molecular biology",
      "subfield": "molecular-biology"
    }
  ],
  "title": "Splicing-guaranteed artificial introns enable efficient homology-directed repair at internal exons and streamlined cell engineering",
  "title_text": "Splicing-guaranteed artificial introns enable efficient homology-directed repair at internal exons and streamlined cell engineering",
  "type": "preprint",
  "updated_at": "2026-10-30T12:28:07Z",
  "url": "https://research.draconitic.com/paper/3dt757cgqkhgr",
  "venue": "bioRxiv",
  "versions": []
}