Prime editing corrects the dilated cardiomyopathy causing RBM20-P633L-mutation in human cardiomyocytes
Roman et al. (2025) demonstrate prime editing efficacy in human iPSC-derived cardiomyocytes — post-mitotic cells with relevance as an OHC analogue. A PE4 strategy targeting the RBM20-P633L dilated cardiomyopathy mutation achieved approximately 35% editing efficiency in terminally differentiated cardiomyocytes, with downstream functional rescue: restored RBM20 protein localization and normalized cardiac splicing patterns for titin and calcium signaling genes. This is the first reported PE phenotypic rescue in a human post-mitotic disease model.
Author note: This paper was cited in the h07 sweep notes as “Chemla 2025 PMID 41210585.” The name “Chemla” does not appear in the author list. The actual first author is Alexandra Roman (Roman et al. 2025). This is a new author-phantom introduced in the sweep; corrected here.
Key finding
~35% prime editing efficiency in human iPSC-derived cardiomyocytes with phenotypic rescue confirms PE is mechanistically compatible with post-mitotic human cells beyond neurons. The functional rescue (splicing normalization) is the critical result — not just editing frequency.
Numbers that matter
| Parameter | Value | Units | Source | Conditions |
|---|---|---|---|---|
| PE4 editing efficiency in cardiomyocytes | ~35 | % (average) | Abstract | Human iPSC-derived CMs, RBM20-P633L disease model |
| Cell type | iPSC-derived cardiomyocytes | — | — | Post-mitotic; differentiated from patient-derived iPSCs |
| Phenotypic rescue | Yes | — | Abstract | RBM20 protein localization restored; titin splicing normalized |
Limitations
- Ex vivo cell model, not in vivo delivery; AAV transduction efficiency in vivo CMs is lower than lentiviral/plasmid ex vivo.
- iPSC-derived CMs are less mature than adult CMs; fetal-like transcriptome may affect PE machinery expression.
- No efficiency breakdown by PE variant optimization steps; “~35%” is the reported average.
- No OHC data; cardiomyocyte → OHC extrapolation assumes similar post-mitotic PE compatibility.
Connections
[source]Prime Editing for STRC — 34.8% cardiomyocyte efficiency; post-mitotic benchmark for h07 OHC extrapolation[part-of]prime-editing — prime-editing topic parameter table[applies]h07 hub — secondary post-mitotic efficiency anchor[see-also]2024-davis-dual-aav-split-prime-editor-brain — complementary post-mitotic PE data (neurons)