TEAD1-Ex5-ASO

TEAD1-Ex5-ASO is a splicing-modulating antisense oligonucleotide (ASO) designed to target the alternative splicing of the Hippo pathway transcription factor TEAD1. In fibrotic liver diseases, such as metabolic dysfunction-associated steatohepatitis (MASH) and primary sclerosing cholangitis (PSC), the nuclear protein TM7SF3 is downregulated, leading to the activation of the splicing factor hnRNPU. This splicing factor mediates the skipping of the inhibitory exon 5 of TEAD1, producing a highly active TEAD1 isoform (TEAD1ΔEx5) that drives hepatic stellate cell (HSC) and portal fibroblast (PF) activation, collagen production, and liver fibrosis. TEAD1-Ex5-ASO binds to the pre-mRNA of TEAD1 just upstream of exon 5, blocking hnRNPU binding and preventing the exclusion of exon 5. By promoting the retention of the inhibitory exon 5, the ASO suppresses the active TEAD1ΔEx5 isoform, deactivates fibrogenic myofibroblasts, and alleviates cholestatic injury and periductal fibrosis.

Other names

TEAD1 alternative splicing-modulating antisense oligonucleotideTEAD-1 alternative splicing-modulating antisense oligonucleotideTEAD 1 alternative splicing-modulating antisense oligonucleotideTEAD1 antisense oligonucleotideTEAD-1 antisense oligonucleotideTEAD 1 antisense oligonucleotide