Dual CRISPR/Cas9 correction of compound heterozygous MARS2 mutations in the iPSC line ISMMSi060-A from a patient with COXPD25

Summary

We previously described the induced pluripotent stem cell (iPSC) line ISMMSi060-A derived from a patient with Combined Oxidative Phosphorylation Deficiency 25 (COXPD25) carrying compound heterozygous pathogenic variants in the mitochondrial methionyl-tRNA synthetase gene, MARS2. Here, we report the generation of the isogenic control line ISMMSi060-A-1 by CRISPR/Cas9-mediated correction of the MARS2 variants c.424C>T (p.Arg142Trp) and c.550C>T (p.Gln184*). The corrected line retained normal morphology, pluripotency, genomic integrity, and differentiation capacity, providing a valuable resource to study MARS2-related mitochondrial dysfunction and therapeutic strategies for COXPD25. Copyright © 2026. Published by Elsevier B.V.

Authors Liu NN, Baljinnyam E, Hu R, Salemi SE, Webb BD, Marro SG
Journal Stem cell research
Publication Date 2026 Jun 19;95:104041
PubMed 42361764
DOI 10.1016/j.scr.2026.104041

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