Targeting fused in sarcoma (FUS): a novel antisense strategy for treating idiopathic pulmonary fibrosis - PubMed
5 hours ago
- #antisense oligonucleotide
- #idiopathic pulmonary fibrosis
- #FUS
- Fused in sarcoma (FUS) is a conserved RNA-binding protein with roles in RNA processing and genomic stability.
- FUS dysregulation is implicated in idiopathic pulmonary fibrosis (IPF), a fibrotic disease.
- The study explores FUS as a therapeutic target in IPF using antisense oligonucleotide (ASO) ION363.
- FUS overexpression promotes fibroblast proliferation, while its knockdown reduces hyperproliferation in IPF fibroblasts.
- IPF fibroblasts show abnormal cytoplasmic mislocalization of FUS.
- Standard IPF treatments (pirfenidone, nintedanib) reduce FUS expression in precision-cut lung slices (PCLs).
- CLIP-Seq identified FUS binding to profibrotic RNAs in IPF.
- ION363 treatment downregulates fibrotic genes related to ECM remodeling, TGFβ signaling, and epithelial dysfunction.
- ION363 improves functional markers and morphology in 3D alveolospheres from IPF patients.
- Targeting FUS via ASO is a promising therapeutic strategy for IPF.