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Adeno-Associated Virus-Mediated Delivery of CRISPR for Cardiac Gene Editing in Mice
Published on: August 2, 2018
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Therapeutic base editing alleviates restrictive cardiomyopathy.
Chong Chang1, Xiulin Zhang2, Xiaoqi Fan3
1College of Life Sciences, Zhejiang University, Hangzhou, Zhejiang, China; State Key Laboratory of Gene Expression, School of Medicine, Westlake University, Hangzhou, Zhejiang 310030, China.
Cell Reports. Medicine
|February 28, 2026
Summary
Adenine base editing (ABE) successfully corrected a mutation causing restrictive cardiomyopathy (RCM) in mice. This gene therapy approach improved cardiac function, offering hope for treating genetic heart conditions.
Area of Science:
- Cardiovascular Medicine
- Genetics
- Molecular Therapy
Background:
- Restrictive cardiomyopathy (RCM) is a severe heart condition impairing diastolic function, often caused by sarcomeric protein mutations.
- Mutations in the TNNI3 gene, such as p.R192H, are significant genetic drivers of RCM, especially in pediatric cases with poor outcomes.
Purpose of the Study:
- To investigate the efficacy of adenine base editing (ABE) in correcting the TNNI3 R193H mutation and alleviating RCM in a mouse model.
- To establish base editing as a potential therapeutic strategy for genetic cardiomyopathies.
Main Methods:
- Development of a murine model with the Tnni3R193H mutation mimicking human RCM.
- Adeno-associated virus (AAV)-mediated delivery of ABE for targeted gene correction in adult RCM mice.
Main Results:
- ABE achieved efficient and precise correction of the Tnni3R193H mutation in the RCM mouse model.
- Significant improvement in cardiac function was observed following ABE treatment.
Conclusions:
- Adenine base editing demonstrates therapeutic potential for RCM by correcting causative mutations.
- This study supports the broader application of base editing for treating genetic cardiomyopathies.
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