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This novel antisense oligonucleotide (ASO) is designed to suppress the expression of all fibronectin (FN) isoforms, including the profibrotic EDA-containing variant. Fibronectin is a core component of the interstitial extracellular matrix (ECM) and is aberrantly expressed in myelofibrosis (MF), where it serves as a scaffold for other matrix proteins and drives megakaryocytic hyperplasia and inflammation. The ASO is a chemically modified 2′-O-(2-methoxyethyl) phosphorothioate (2'-MOE) oligonucleotide that effectively silences cellular FN splice variants. In preclinical models of myelofibrosis, systemic administration of the FN ASO significantly reduced bone marrow fibrosis (reticulin deposition), attenuated megakaryocyte expansion, and decreased levels of fibrogenic cytokines such as TGF-β1 and IL-6. It represents a direct anti-fibrotic strategy aimed at disrupting ECM remodeling and disease progression in hematologic malignancies and potentially other fibrotic diseases.
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