Cardiomyocyte-specific lamin A re-expression via AAV-Lmna/DJ8 ameliorates cardiac dysfunction in Lmna⁻/⁻ mice

We investigated whether re-expression of lamin A in cardiomyocytes can rescue the severe phenotype of Lmna⁻/⁻ mice. An adeno-associated virus vector expressing wild-type Lmna (AAV-Lmna/DJ8) was administered intrathoracically to neonatal mice.

Three weeks after injection, treated Lmna⁻/⁻ mice exhibited robust cardiac Lmna mRNA induction and nuclear localization of lamin A protein, reflecting efficient cardiotropic gene delivery. Compared with PBS treatment, AAV-Lmna/DJ8 treatment promoted body weight maintenance, improved left ventricular systolic function, and significantly prolonged survival in Lmna⁻/⁻ mice. To explore the underlying mechanisms, we performed single-nucleus RNA sequencing of cardiomyocytes from wild-type mice, PBS-treated Lmna⁻/⁻ mice, and AAV-Lmna/DJ8–treated Lmna⁻/⁻ mice.