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Poly(rC)-binding protein 2 (PCBP2) mRNA encodes a multifunctional RNA-binding protein that plays a critical role in post-transcriptional regulation, including mRNA stabilization and translational control (UniProt Q15366). In the context of fibrotic diseases, PCBP2 is known to stabilize the mRNA of Type I collagen, thereby promoting the excessive deposition of extracellular matrix in organs like the liver and pancreas (PMID: 23536554). Therapeutic strategies targeting PCBP2 mRNA utilize small interfering RNA (siRNA) to induce its degradation, effectively reducing the production of the PCBP2 protein and subsequently decreasing collagen synthesis. A prominent example is BMS-986263 (formerly ND-L02-s0201), a vitamin A-coupled lipid nanoparticle carrying siRNA, which specifically targets activated hepatic stellate cells to treat liver fibrosis (PMID: 28811273). Beyond fibrosis, PCBP2 is involved in the life cycle of various RNA viruses, such as Poliovirus and Hepatitis C, by binding to internal ribosome entry sites (IRES) to facilitate viral translation. Consequently, PCBP2 mRNA represents a high-value target for RNA-based therapeutics aiming to modulate protein expression in chronic inflammatory and fibrotic conditions.
RNA interference (siRNA-mediated degradation of PCBP2 mRNA to reduce protein expression)
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