Genomic Editing of a Pathogenic Sequence Variant in <i>ACTA2</i> Rescues Multisystemic Smooth Muscle Dysfunction Syndrome in Mice
This study demonstrates the effectiveness of adenine base editing to treat multisystemic smooth muscle dysfunction syndrome and restore aortic smooth muscle function. By correcting the <i>ACTA2</i> R179H sequence variant, the pathogenic phenotypic shift in SMCs was prevented, key aortic smooth muscle functions were restored, and life-threatening aortic dilation and dissection were mitigated in humanized mice. These findings underscore the promise of gene-editing therapies in addressing the underlying genetic causes of smooth muscle disorders and offer a potential transformative treatment for patients facing severe vascular complications.
Authors
- Yu Zhang (ORCID: https://orcid.org/0000-0003-3384-8887)
- Peiheng Gan (ORCID: https://orcid.org/0000-0001-8617-0606)
- John McAnally (ORCID: https://orcid.org/0000-0001-6938-2703)
- Lei Guo
- Dileep Karri (ORCID: https://orcid.org/0000-0001-6404-8386)
- Cameron M. Macdonald
- Lin Xu (ORCID: https://orcid.org/0000-0001-5815-4457)
- Eric N. Olson (ORCID: https://orcid.org/0000-0003-1151-8262)
- Efrain Sanchez‐Ortiz (ORCID: https://orcid.org/0000-0001-9358-1630)
- Wei Hong Tan (ORCID: https://orcid.org/0000-0001-6008-3854)
- Hui Li (ORCID: https://orcid.org/0000-0002-4114-8349)
- Ning Liu (ORCID: https://orcid.org/0000-0003-0257-1889)
- Zhi‐Sheng Xu (ORCID: https://orcid.org/0000-0002-5780-3803)
- Qianqian Ding
Institutions
- Southwestern Medical Center (US)
- The University of Texas Southwestern Medical Center (US)
Publication Details
- Journal
- Circulation
- Published
- 2025-05-16
- DOI
- https://doi.org/10.1161/circulationaha.125.074218
- Citations
- 6
- Primary Topic
- CRISPR and Genetic Engineering
- Type
- article
- Field-Weighted Citation Impact
- 4.84