{
  "abstract": "Our objective is to develop a universal gene editing therapeutic for individuals with cystic fibrosis (CF). Due to the large number of CFTR variants, we sought to develop a correction methodology utilizing targeted integration of CFTR 2-27 sequence into CFTR intron 1 (TI-1). Following electroporation of CF primary airway basal stem cells with intron 1-targeted Cas9/gRNA, we delivered CFTR 2-27 donor, flanked by a splice acceptor and polyadenylation signal, via an integrase defective lentiviral vector. Molecular characterization revealed highly efficient integration of the CFTR 2-27 sequence into the native CFTR intron 1 with most insertion events reflecting the desired homology-directed repair. Fully differentiated airway epithelium, derived from TI-1 treated basal cells without enrichment for corrected cells, exhibited functional restoration of CFTR channel activity with significant improvement of mucus hydration and transport. ATAC-seq revealed that the native CFTR chromatin architecture was unaffected by the CFTR 2-27 sequence insertion, and importantly, scRNA-seq demonstrated that the cell-type-specific expression of the introduced transgene replicated that of the endogenous CFTR . In this report, we demonstrate an almost completely mutation-agnostic therapeutic approach that is capable of functional CFTR restoration. These results may also be relevant to CFTR 2-27 integration via other editing and delivery methodologies.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA; Center for Stem Cells and Regenerative Medicine, University of Texas Health Science Center at Houston, Houston, TX 77030, USA",
    "Department of Bioengineering, Rice University, Houston, TX 77030, USA",
    "Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA",
    "Gregory Fleming James Cystic Fibrosis Research Center, University of Alabama at Birmingham, Birmingham, AL 35294, USA",
    "Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA; Gregory Fleming James Cystic Fibrosis Research Center, University of Alabama at Birmingham, Birmingham, AL 35294, USA",
    "Department of Genetics and Genome Sciences, Case Western Reserve University, Cleveland, OH 44106, USA",
    "Cystic Fibrosis Foundation Therapeutics Lab, Cystic Fibrosis Foundation, Lexington, MA 02421, USA",
    "Gregory Fleming James Cystic Fibrosis Research Center, University of Alabama at Birmingham, Birmingham, AL 35294, USA; Department of Biochemistry and Molecular Genetics, University of Alabama at Birmingham, Birmingham, AL 35294, USA",
    "Department of Pediatrics, School of Medicine, Emory University, Atlanta, GA 30322, USA"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 23,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Cristina Barillà"
    },
    {
      "name": "Shingo Suzuki"
    },
    {
      "affs": [
        1
      ],
      "name": "So Hyun Park"
    },
    {
      "affs": [
        2
      ],
      "name": "Divyasri Nalluri"
    },
    {
      "affs": [
        3
      ],
      "name": "Hui Wen"
    },
    {
      "affs": [
        4
      ],
      "name": "Mohamed A. Hanafy"
    },
    {
      "affs": [
        1
      ],
      "name": "Daniel Betancourth"
    },
    {
      "affs": [
        5
      ],
      "name": "Ayushi Umrigar"
    },
    {
      "affs": [
        5
      ],
      "name": "Shih-Hsing Leir"
    },
    {
      "affs": [
        5
      ],
      "name": "Katreya Lovrenert"
    },
    {
      "affs": [
        6
      ],
      "name": "Andrey Sivachenko"
    },
    {
      "affs": [
        6
      ],
      "name": "Barbara Tabak"
    },
    {
      "affs": [
        7
      ],
      "name": "Zhong Liu"
    },
    {
      "affs": [
        7
      ],
      "name": "Rui Zhao"
    },
    {
      "affs": [
        6
      ],
      "name": "Hillary C. Valley"
    },
    {
      "affs": [
        8
      ],
      "name": "Andras Rab"
    },
    {
      "affs": [
        8
      ],
      "name": "Eric J. Sorscher"
    },
    {
      "affs": [
        4
      ],
      "name": "George M. Solomon"
    },
    {
      "affs": [
        6
      ],
      "name": "Martin Mense"
    },
    {
      "affs": [
        6
      ],
      "name": "John P. Carulli"
    },
    {
      "affs": [
        5
      ],
      "name": "Ann Harris"
    },
    {
      "affs": [
        1
      ],
      "name": "Gang Bao"
    },
    {
      "name": "Brian R. Davis"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/d0n8jwpb941re.bib",
  "cited_by": 0,
  "doi": "10.1016/j.omtn.2026.103123",
  "fulltext_url": "http://www.sciencedirect.com/science/article/pii/S2162253126002945",
  "id": "d0n8jwpb941re",
  "issns": [
    "2162-2531"
  ],
  "landing_url": "https://doi.org/10.1016/j.omtn.2026.103123",
  "language": "en",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Original Article"
    ],
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      "lcc",
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      "openalex",
      "2740|Cystic Fibrosis Research Advances"
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  "pdf_url": "https://europepmc.org/articles/PMC13717110?pdf=render",
  "pmcid": null,
  "pmid": "42959355",
  "published": "2026-10-01",
  "publisher": "Elsevier",
  "ris": "https://research.draconitic.com/paper/d0n8jwpb941re.ris",
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      "native_id": "PMC13717110",
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      "url": "https://doi.org/10.1016/j.omtn.2026.103123"
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  "subjects": [
    {
      "field": "biochemistry",
      "origin": "journal-openalex:1312|RNA Interference and Gene Delivery",
      "subfield": "molecular-biology"
    },
    {
      "field": "medicine",
      "origin": "lcc:RM1-950",
      "subfield": "pharmacology-toxicology"
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  ],
  "title": "Targeted insertion of partial",
  "title_text": "Targeted insertion of partial",
  "type": "peer-reviewed",
  "updated_at": "2026-11-02T12:21:29Z",
  "url": "https://research.draconitic.com/paper/d0n8jwpb941re",
  "venue": "Molecular Therapy: Nucleic Acids",
  "versions": []
}