{
  "abstract": "Homozygosity for the HBB codon 8/9 (+G) frameshift (c.27dup (p.Ser10ValfsTer14)) causes transfusion-dependent {beta}-thalassaemia and is common in South Asia. Prime editing can reverse this insertion without double-strand breaks or donor DNA, but its efficiency depends on pegRNA design. We derived Sendai-reprogrammed iPSCs from a homozygous patient, optimised PEmax editing (spacer, pegRNA extension, secondary nick, MLH1dn) and compared patient, PEmax-treated and control iPSC-derived erythroid cells by flow cytometry, colony assays, RT-qPCR, western blotting and cation-exchange HPLC. Patient iPSCs had a normal 46,XY karyotype, expressed pluripotency markers, formed all three germ layers and were Sendai-free by passage 15. A PAM-disrupting spacer with a +68 nicking sgRNA gave the highest intended-edit frequency 8.4%; MLH1dn added little. PEmax-treated cultures matured and formed colonies more like control than patient cultures, restored HBB transcript (about 4-fold control iPSC-derived cells) and detectable {beta}-globin protein, and contained an HPLC fraction consistent with HbA ( undetectable in patient cells). Fetal haemoglobin (about 80%) and embryonic globin remained predominant. Prime editing corrects HBB c.27dupG in patient iPSCs and restores {beta}-globin expression, with partial restoration of adult haemoglobin in a fetal/embryonic-type erythroid background. Validation in additional donors, haematopoietic stem cells and in vivo is required.",
  "abstract_shown": true,
  "affiliations": [
    "Centre for Regenerative Medicine and Stem Cell Research, Aga Khan University, Karachi, Pakistan"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 13,
  "authors": [
    {
      "name": "i. hussain"
    },
    {
      "name": "K. Mumtaz"
    },
    {
      "name": "M. Javed"
    },
    {
      "name": "S. Fatima"
    },
    {
      "name": "H. Zahra"
    },
    {
      "name": "A. Alam"
    },
    {
      "name": "M. Jameel"
    },
    {
      "name": "N. A. Malik"
    },
    {
      "name": "F. Syed"
    },
    {
      "name": "F. U. Rehman"
    },
    {
      "name": "S. Kirmani"
    },
    {
      "name": "A. Fatima"
    },
    {
      "affs": [
        0
      ],
      "name": "A. A. Mian"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/et2kd5cpkb472.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.09.22.753453",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.09.22.753453v1.full",
  "id": "et2kd5cpkb472",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.09.22.753453v1",
  "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",
      "cell biology"
    ],
    [
      "openalex",
      "1312|CRISPR and Genetic Engineering"
    ]
  ],
  "openalex": "W7214241379",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.09.22.753453v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-22",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/et2kd5cpkb472.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:24:25Z",
      "native_id": "10.64898/2026.09.22.753453",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.09.22.753453v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:cell biology",
      "subfield": "cell-biology"
    }
  ],
  "title": "Prime Editing Corrects the HBB Codon 8/9 (+G) Mutation in Patient-Derived Induced Pluripotent Stem Cells and Restores β-Globin Expression in iPSC-Derived Erythroid Cells",
  "title_text": "Prime Editing Corrects the HBB Codon 8/9 (+G) Mutation in Patient-Derived Induced Pluripotent Stem Cells and Restores β-Globin Expression in iPSC-Derived Erythroid Cells",
  "type": "preprint",
  "updated_at": "2026-10-30T12:24:25Z",
  "url": "https://research.draconitic.com/paper/et2kd5cpkb472",
  "venue": "bioRxiv",
  "versions": []
}