Work

RNAi-mediated p38δ silencing mitigates anthracycline cardiotoxicity in female mice

Year: 2026

Type: article

Abstract: This study presents the first isoform-specific inhibition of p38δ using a docosanoic (DCA)-conjugated, fully chemically stabilized siRNA. Our lead compound, si644, achieves potent, durable, and well-tolerated p38δ silencing in vivo in mouse hearts and ex vivo in human cardiac organotypic slices. si644-mediated p38δ silencing protects female mice from DIC by mitigating DOX-induced structural, electrophysiological, fibrotic, and inflammatory remodeling. These findings establish p38δ inhibition as a promising therapeutic strategy for preventing anthracycline cardiotoxicity.

Source: American Journal of Physiology-Heart and Circulatory Physiology

DOI: 10.1152/ajpheart.00944.2025