TUNE-401

TUNE-401 is a first-in-class investigational epigenetic silencing therapy developed for the treatment of chronic Hepatitis B virus (HBV) infection. It is designed to target and silence both integrated HBV DNA and covalently closed circular DNA (cccDNA) at the epigenetic level, without cutting or editing the host genome. The therapy uses lipid nanoparticles to deliver mRNA encoding a catalytically-dead Cas9 (dCas9) fused to two effector domains—a methyltransferase and another epigenetic repressor—along with a guide RNA targeting conserved HBV sequences. Once inside liver cells, this construct induces targeted DNA methylation and heterochromatin formation at HBV loci, leading to robust repression of viral gene expression and production of new viral particles. Preclinical studies have demonstrated up to 99.99% suppression of HBV RNA from cccDNA in infected human hepatocytes, with durable effects lasting over 550 days in cell models[1][2][3][4][5][6][8]. TUNE-401 is currently entering Phase 1b clinical trials as the first epigenetic therapy for an infectious disease.

Other names

Epigenetic silencer for HepBTune HBV epigenetic silencer