Wisp2 super-enhancer-associated RNA (Wisper)

Wisp2 super-enhancer-associated RNA, commonly known as Wisper, is a cardiac fibroblast-enriched long noncoding RNA (lncRNA) transcribed from a super-enhancer region proximal to the Wisp2 (CCN5) gene [1, 6]. It plays a pivotal role in the regulation of cardiac fibrosis and pathological remodeling following myocardial injury [1, 4]. Wisper functions by controlling gene expression programs essential for cardiac fibroblast identity, proliferation, migration, and survival [2, 9]. Specifically, it interacts with TIA1-related protein (TIAR) to regulate the alternative splicing of lysyl hydroxylase 2 (Plod2), which is critical for collagen stabilization and extracellular matrix cross-linking [1, 8]. Because its expression is highly specific to the heart and correlates with the severity of fibrosis in patients, Wisper is considered a promising therapeutic target for heart failure and hypertrophic cardiomyopathy [10, 19]. The lead therapeutic candidate, HTX-001, is an antisense oligonucleotide designed to silence Wisper and attenuate fibrotic progression [19, 25].

Other names

WisperWISPERWIsp2 SuPer-Enhancer associated RNACardiac fibroblast-enriched long noncoding RNA

Antisense oligonucleotide-mediated silencing (knockdown) of the lncRNA to inhibit pro-fibrotic gene programs and reduce collagen cross-linking in cardiac fibroblasts.