Hepatitis B virus messenger RNA (HBV mRNA)

Hepatitis B virus (HBV) messenger RNA (mRNA) encompasses all viral transcripts produced from the covalently closed circular DNA (cccDNA) or integrated viral DNA in infected hepatocytes [1, 31]. These transcripts include the pregenomic RNA (pgRNA), which serves as the template for reverse transcription and encodes the core and polymerase proteins, as well as subgenomic mRNAs encoding the surface (HBsAg) and X (HBx) proteins [1, 18]. Targeting well-conserved genomic regions across multiple HBV genotypes (A-J) is a key therapeutic strategy to ensure broad efficacy and prevent viral escape [1, 30]. Drugs such as BB-HB-331 utilize DNA-directed RNA interference (ddRNAi) to express short hairpin RNAs (shRNAs) that simultaneously target three such regions (typically Core, S, and X), leading to the degradation of all viral transcripts [30, 35]. This reduction in viral RNA levels results in a significant decrease in the production of all viral proteins, which is hypothesized to alleviate immune exhaustion and facilitate a functional cure for chronic hepatitis B [1, 31]. Other modalities, such as small interfering RNAs (siRNAs) like JNJ-3989 and VIR-2218, or antisense oligonucleotides (ASOs) like bepirovirsen, also target these transcripts to suppress viral replication and antigenemia [2, 4, 32].

Other names

HBV transcriptsHepatitis B virus RNAHBV RNAHBV pregenomic RNA (pgRNA)HBV subgenomic RNA

RNA interference (RNAi), antisense inhibition, and shRNA-mediated degradation of viral transcripts.