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Therapeutic base editing alleviates restrictive cardiomyopathy

GSE295799 Mus musculus Expression profiling by high throughput sequencing 6 samples Submitted 2025/04/30 Platform GPL34290
Summary
Restrictive cardiomyopathy (RCM) is a severe cardiac disorder characterized by impaired ventricular filling and diastolic dysfunction, with mutations in sarcomeric proteins representing major causative factors. Mutations of TNNI3 gene (e.g. p.R192H) constitute major genetic causes of RCM, particularly affecting pediatric patients and being associated with poor prognosis. Here, we demonstrate that adenine base editor (ABE) is able effectively correct RCM-causing mutation and alleviate RCM in a murine model. We first developed a novel murine model harboring the Tnni3R193H mutation that recapitulates the hallmark features of human RCM. Importantly, targeted delivery of ABE via adeno-associated virus (AAV) achieved efficient and precise correction of the Tnni3R193H mutation in adult RCM mice, leading to significant improvement of cardiac functions. Our findings establish base editing as a therapeutic strategy for RCM and highlight its broader potential for treating genetic cardiomyopathies in clinical settings.
Published in
Therapeutic base editing alleviates restrictive cardiomyopathy
Chang C, Zhang X, Fan X et al. · Cell reports. Medicine 2026 · PMID 41763217 · doi:10.1016/j.xcrm.2026.102639
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Also filed as BioProject PRJNA1256393 and SRA study SRP581938. Searching any of these in the dataset finder brings you back here.

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