Identification of potent siRNA targeting complement C5 and its robust activity in pre-clinical models of myasthenia gravis and collagen-induced arthritis.

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 in vitro IC₅₀ of 420 pM and in vivo ED₅₀ of 0.017 mg/kg following a single administration. Single or repeated administrations of the LNP-formulated C

SUBMITTER: Kuboi Y 

PROVIDER: S-EPMC9900455 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature