CRISPR/Cas9-mediated editing of XPA in induced pluripotent stem cells: A model for investigating Xeroderma Pigmentosum and NER dysfunction

Summary

Xeroderma pigmentosum group A (XPA) is caused by defects in the nucleotide excision repair (NER) pathway, which is essential for repairing UV-induced DNA damage. Mutations in XPA impair lesion recognition and repair, resulting in mutation accumulation, genomic instability, and a high risk of skin cancers. In this study, we generated a CRISPR/Cas9-engineered human induced pluripotent stem cell (iPSC) line, WTSIi018-B-30, carrying a homozygous single nucleotide variant in exon 3 of XPA. The edited iPSCs retained normal morphology, expressed pluripotency markers, and differentiated into all three germ layers. This mutant iPSC line provides a robust isogenic model to dissect the molecular consequences of XPA deficiency and to explore therapeutic strategies for XPA-associated diseases. Copyright © 2025 The Author(s). Published by Elsevier B.V. All rights reserved.

Authors Papadopoulou M, Ramachandran H, Binder S, Hildebrandt B, Rossi A, Krutmann J
Journal Stem cell research
Publication Date 2025 Nov 15;89:103869
PubMed 41265249
DOI 10.1016/j.scr.2025.103869

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