An RNA interference therapeutic potentially achieves functional cure of chronic hepatitis B virus infection.

ABSTRACT: Current therapeutics for chronic hepatitis B virus (HBV) infection are insufficient due to immune exhaustion caused by high circulating hepatitis B surface antigen (HBsAg) levels. Here, an HBV S region-targeted small interfering RNA (siRNA) is reported, aiming to dramatically suppress HBsAg and provide windows for host immune restoration. This siRNA agent, called KC13-M2G2, exhibits potent antiviral efficacy against all HBV genotypes in vitro. Notably, in multiple mouse models, KC13-M2G2 triggers rapid and sustained loss of HBsAg and HBV DNA accompanied by hepatitis B surface antibody seroconversion, outperforming the clinical drug elebsiran and bepirovirsen. Toxicity studies in Sprague-Dawley rats and cynomolgus monkeys indicate satisfactory biosafety profiles of KC13-M2G2. Given that ele

SUBMITTER: Huang ZA 

PROVIDER: S-EPMC12780110 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature