Base editing used to generate iPSC model collection for centronuclear myopathy

Researchers have posted a preprint to bioRxiv describing iPS-CNM, a collection of induced pluripotent stem cell (iPSC) lines engineered to carry distinct mutations associated with centronuclear myopathy (CNM), a rare inherited muscle disease characterised by progressive weakness and abnormal positioning of nuclei within muscle fibres.

CNM is genetically heterogeneous, with pathogenic variants identified in genes including MTM1, DNM2, BIN1, and RYR1, among others. Studying CNM has historically been complicated by this mutation diversity and by differences in genetic background between patient-derived cell lines, which make it difficult to attribute observed cellular phenotypes specifically to the disease variant rather than to broader genomic differences between individuals.

The iPS-CNM approach addresses this by using base editing — a form of genome editing that chemically converts one DNA base to another without making double-strand breaks — to introduce specific CNM-associated mutations directly into a single iPSC line derived from a healthy donor. This creates a matched panel of lines that differ only at the introduced variant, enabling cleaner comparisons.

The preprint describes optimisation of base editor selection and guide RNA design, noting that editing efficiency was strongly dependent on both the choice of base editor variant and the target sequence context. The resulting collection is positioned as a community resource for CNM research and, more broadly, as a demonstration of the base-editing-for-disease-modelling workflow. As a preprint, the work has not yet undergone peer review.