Adenine Base Editing Potently Suppresses Hepatitis B Surface Antigen Expression and Inhibits Hepatitis D Virus Release.

ABSTRACT:

Background and aims

Novel antiviral approaches capable of permanently inactivating the intrahepatic HBV DNA reservoir, the covalently closed circular DNA (cccDNA) and HBV DNA integrated into the host genome, are urgently needed. This study evaluated adenine base editing as a strategy to disrupt HBV replication by introducing mutations in the overlapping HBs/polymerase open reading frame (ORF).

Methods

An adenine base editor (ABE) and 3 guide RNAs (gS1-gS3) were designed to introduce missense mutations within the HBs/polymerase ORF. ABE mRNA and individual gRNAs were co-transfected into HBV-infected HepG2-hNTCP cells and primary human hepatocytes. Antiviral efficacy was further assessed in HepG2.2.15 and PLC/PRF/5 cells harboring integrated HBV DNA. In vivo, lipid nanoparticl

SUBMITTER: Kumar A 

PROVIDER: S-EPMC12889661 | biostudies-literature | 2026 Feb

REPOSITORIES: biostudies-literature