Hepatitis B virus surface antigen messenger RNA (HBsAg mRNA) (HBsAg mRNA)

Hepatitis B virus (HBV) surface antigen (HBsAg) mRNA transcripts are the viral messenger RNAs responsible for the synthesis of the large, middle, and small surface proteins of HBV [14, 17, 20]. These transcripts, primarily the 2.4 kb and 2.1 kb RNAs, are transcribed from the intrahepatic covalently closed circular DNA (cccDNA) or from integrated viral DNA in the host genome [14, 17, 20]. HBsAg plays a critical role in the viral lifecycle by mediating viral entry into hepatocytes and forming subviral particles that circulate in high concentrations, which are thought to exhaust the host's immune system and prevent viral clearance [3, 9, 14]. Targeting these mRNA transcripts with RNA interference (RNAi) or antisense oligonucleotides (ASOs) aims to reduce HBsAg production, potentially restoring the host's immune response and achieving a functional cure (sustained HBsAg loss) [1, 4, 7]. Clinical candidates like bepirovirsen and various siRNAs are currently being evaluated for their ability to potently and durably suppress these transcripts [2, 3, 10]. By degrading these transcripts, these therapies can simultaneously lower the levels of all viral proteins and replication intermediates, as many HBV transcripts share a common 3' polyadenylation signal [1, 14]. This approach is distinct from current nucleos(t)ide analogues, which inhibit reverse transcription but do not directly reduce the production of viral antigens [14, 18]. Successful suppression of HBsAg mRNA is considered a key step toward enabling the host immune system to regain control over the infection [4, 9].

Other names

HBV S mRNAHBsAg transcriptsPre-S1/Pre-S2/S mRNAHepatitis B virus surface antigen transcripts

RNA interference (siRNA) and RNase H-mediated degradation (ASO) of viral mRNA transcripts to inhibit the translation of Hepatitis B surface antigens and other viral proteins [1, 2, 4, 11, 18].