Genomic Editing of a Pathogenic Sequence Variant in <i>ACTA2</i> Rescues Multisystemic Smooth Muscle Dysfunction Syndrome in Mice.

ABSTRACT:

Background

Vascular smooth muscle cells (SMCs), the predominant cell type in the aortic wall, play a crucial role in maintaining aortic integrity, blood pressure, and cardiovascular function. Vascular SMC contractility and function depend on ACTA2 (smooth muscle α-actin 2). The pathogenic variant ACTA2 c.536G>A (p.R179H) causes multisystemic smooth muscle dysfunction syndrome, a severe disorder marked by widespread smooth muscle abnormalities, resulting in life-threatening aortic disease and high risk of early death from aneurysms or stroke. No effective treatments exist for multisystemic smooth muscle dysfunction syndrome.

Methods

To develop a comprehensive therapy for multisystemic smooth muscle dysfunction syndrome, we used CRISPR (clustered regularly interspaced s

SUBMITTER: Ding Q 

PROVIDER: S-EPMC12220935 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature