簡介:
- 作者: Chong Chang, Xiulin Zhang, Xiaoqi Fan, Xiao Chen, Jiangping Song, Xing Chang
- 雜志: Cell Reports Medicine
- Doi: https://www.doi.org/10.1016/j.xcrm.2026.102639
- 出版日期: 2026/2/27
摘要
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) can effectively correct RCM-causing mutation and alleviate RCM in a murine model. We develop a murine model harboring the Tnni3R193H mutation that recapitulates the hallmark features of human RCM. Importantly, targeted delivery of ABE via adeno-associated virus (AAV) can achieve 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.
關于派真
作為一家專注于AAV 技術十余年,深耕基因治療領域的CRO&CDMO,派真生物可提供從載體設計、構建到 AAV、慢病毒和 mRNA 服務的一站式解決方案。憑借深厚的技術實力、卓越的運營管理和高標準的服務交付,我們為全球客戶提供一站式CMC解決方案,包括從早期概念驗證、成藥性評估到IIT、IND及BLA的各個階段。
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憑借我們獨立知識產權的π-alphaTM 293 細胞AAV高產技術平臺,我們能將AAV產量提高多至10倍,每批次產量可達1×101?vg,以滿足多樣化的商業化和臨床項目需求。此外,我們定制化的mRNA和脂質納米顆粒(LNP)產品及服務覆蓋藥物和疫苗開發的各個階段,從研發到符合GMP的生產,提供端到端的一站式解決方案。