Hepatitis B virus surface antigen mRNA (HBsAg mRNA)

Hepatitis B virus surface antigen (HBsAg) mRNA transcripts are essential viral components that encode the surface proteins (S, M, and L) necessary for virion assembly and the production of subviral particles (PubMed: 26230188). These transcripts are produced from both the episomal covalently closed circular DNA (cccDNA) and HBV DNA integrated into the host genome, the latter being a significant source of HBsAg in HBeAg-negative chronic hepatitis B patients (PubMed: 31133510). High levels of circulating HBsAg are associated with the suppression of HBV-specific T-cell and B-cell responses, facilitating viral persistence and the development of chronic liver disease, including cirrhosis and hepatocellular carcinoma (PubMed: 25865837). Therapeutic strategies targeting these mRNA transcripts, such as antisense oligonucleotides (e.g., bepirovirsen) and small interfering RNAs (e.g., JNJ-3989, VIR-2218), aim to degrade the RNA templates and silence HBsAg production (NEJM: 3644540). This reduction in viral antigen load is hypothesized to restore host immune competence, potentially leading to a functional cure of the infection, defined as sustained HBsAg loss (PubMed: 33493414). Unlike nucleos(t)ide analogues that primarily inhibit reverse transcription, RNA-targeting agents can reduce HBsAg derived from both cccDNA and integrated DNA sources, addressing a major barrier to viral clearance (PubMed: 30215685).

Other names

Hepatitis B virus surface antigen open reading frame mRNA transcriptsHBV S-mRNAHBsAg transcriptsHBV surface mRNAHepatitis B virus S gene transcripts

Antisense oligonucleotide (ASO) or RNA interference (RNAi) mediated degradation of viral mRNA transcripts to inhibit HBsAg synthesis.