{
  "abstract": "IntroductionMyeloperoxidase (MPO) is a key neutrophil heme peroxidase that contributes to antimicrobial oxidative killing. Emerging evidence implicates MPO in diverse inflammatory disorders, including atherosclerosis, autoimmune diseases, and neurodegenerative diseases. Since inherited MPO-deficiency is typically compatible with preserved host defense, inhibition or genetic deletion of MPO represents a promising strategy to mitigate MPO-driven tissue injury.MethodsHuman HSPCs were edited using CRISPR-Cas9 to generate MPO-knockout (MPO-KO) neutrophils, followed by in vitro differentiation. We systematically evaluated canonical neutrophil effector functions to determine which of them require MPO. Additionally, RAG2-KO was generated and used as a control for knockout procedure.ResultsMPO-KO did not significantly impair major neutrophil effector functions, including neutrophil elastase activity, fMLP-induced NE and MMP9 degranulation, phagocytosis of E. coli and S. aureus bioparticles, and superoxide production. In contrast, MPO-dependent chlorination was abolished and PMA-induced neutrophil extracellular trap (NET) release was profoundly reduced in MPO-KO neutrophils, while RAG2-KO control cells retained all of these functions.ConclusionThis strategy may offer a durable means to attenuate MPO-driven inflammatory damage, warranting further preclinical evaluation in relevant disease models.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": "Original Research",
  "arxiv": null,
  "author_total": 9,
  "authors": [
    {
      "name": "Szilvia Baron"
    },
    {
      "name": "Aurélien B. L. Colamartino"
    },
    {
      "name": "Jenny Shapiro"
    },
    {
      "name": "Yeshai Schary"
    },
    {
      "name": "Zulema Romero Garcia"
    },
    {
      "name": "Donald B. Kohn"
    },
    {
      "name": "Anat Kahana"
    },
    {
      "name": "Ronit Elhasid"
    },
    {
      "name": "Rachel Shukrun"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/d2rf1rsey9efq.bib",
  "cited_by": 0,
  "doi": "10.3389/fimmu.2026.1970785",
  "fulltext_url": null,
  "id": "d2rf1rsey9efq",
  "issns": [
    "1664-3224"
  ],
  "landing_url": "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1970785",
  "language": null,
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "feed-journal",
      "biology/immunology"
    ]
  ],
  "openalex": null,
  "pdf_url": null,
  "pmcid": null,
  "pmid": null,
  "published": "2026-11-04",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/d2rf1rsey9efq.ris",
  "sources": [
    {
      "first_seen": "2026-11-04T12:20:47Z",
      "native_id": "10.3389/fimmu.2026.1970785",
      "source": "feed-frontiers",
      "url": "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1970785"
    },
    {
      "first_seen": "2026-11-05T00:21:02Z",
      "native_id": "10.3389/fimmu.2026.1970785",
      "source": "crossref",
      "url": "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1970785/full"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "feed-journal:biology/immunology",
      "subfield": "immunology"
    }
  ],
  "title": "Engineering innate immunity: CRISPR-Cas9 MPO knockout in hematopoietic stem cells abolishes chlorination and PMA-induced NET formation while preserving non-oxidative effector functions",
  "title_text": "Engineering innate immunity: CRISPR-Cas9 MPO knockout in hematopoietic stem cells abolishes chlorination and PMA-induced NET formation while preserving non-oxidative effector functions",
  "type": "peer-reviewed",
  "updated_at": "2026-11-06T00:21:18Z",
  "url": "https://research.draconitic.com/paper/d2rf1rsey9efq",
  "venue": "Frontiers in Immunology",
  "versions": []
}