{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Kuboi Y"],"funding":["Japan Agency for Medical Research and Development","Eisai Canada"],"pagination":["339-351"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9900455"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["31"],"pubmed_abstract":["Complement component 5 (C5), an important molecule in the complement cascade, blockade by antibodies shows clinical efficacy in treating complement-mediated disorders. However, insufficient blockading induced by single-nucleotide polymorphisms in the C5 protein or frequent development of \"breakthrough\" intravascular hemolysis in patients with paroxysmal nocturnal hemoglobinuria treated with eculizumab have been reported. Herein, we developed a lipid nanoparticle (LNP)-formulated siRNA targeting C5 that was efficiently delivered to the liver and silenced C5 expression. We identified a potent C5-siRNA with an <i>in vitro</i> IC<sub>50</sub> of 420 pM and <i>in vivo</i> ED<sub>50</sub> of 0.017 mg/kg following a single administration. Single or repeated administrations of the LNP-formulated C"],"journal":["Molecular therapy. Nucleic acids"],"pubmed_title":["Identification of potent siRNA targeting complement C5 and its robust activity in pre-clinical models of myasthenia gravis and collagen-induced arthritis."],"pmcid":["PMC9900455"],"funding_grant_id":["JP17pc0101019"],"pubmed_authors":["Nakatani T","Toritsuka N","Tahara K","Kuboi Y","Suzuki Y","Tomimatsu A","Ida Y","Soejima M","Matsui C","Motoi S","Takahashi Y","Imai T"],"additional_accession":[]},"is_claimable":false,"name":"Identification of potent siRNA targeting complement C5 and its robust activity in pre-clinical models of myasthenia gravis and collagen-induced arthritis.","description":"Complement component 5 (C5), an important molecule in the complement cascade, blockade by antibodies shows clinical efficacy in treating complement-mediated disorders. However, insufficient blockading induced by single-nucleotide polymorphisms in the C5 protein or frequent development of \"breakthrough\" intravascular hemolysis in patients with paroxysmal nocturnal hemoglobinuria treated with eculizumab have been reported. Herein, we developed a lipid nanoparticle (LNP)-formulated siRNA targeting C5 that was efficiently delivered to the liver and silenced C5 expression. We identified a potent C5-siRNA with an <i>in vitro</i> IC<sub>50</sub> of 420 pM and <i>in vivo</i> ED<sub>50</sub> of 0.017 mg/kg following a single administration. Single or repeated administrations of the LNP-formulated C","dates":{"release":"2023-01-01T00:00:00Z","publication":"2023 Mar","modification":"2026-07-14T15:44:50.983Z","creation":"2025-04-06T02:55:15.769Z"},"accession":"S-EPMC9900455","cross_references":{"pubmed":["36789273"],"doi":["10.1016/j.omtn.2023.01.005"]}}