Hepatitis B virus RNA encoding small hepatitis B surface antigen (HBV S-mRNA) (HBV S-mRNA)

The Hepatitis B virus (HBV) RNA encoding the small surface antigen (HBsAg) is a critical component of the viral life cycle and a primary target for novel functional cure therapies (PubMed: 34161727). This RNA transcript, primarily the 2.1 kb subgenomic mRNA, serves as the template for the synthesis of the small S protein, which is the major component of the viral envelope and subviral particles (NCBI: NC_003977.2). In chronic HBV infection, HBsAg is produced in vast excess, acting as an immunological decoy that exhausts the host's immune system and prevents viral clearance (PubMed: 32659777). By targeting this specific RNA sequence using antisense oligonucleotides (ASOs) or small interfering RNAs (siRNAs), clinicians aim to drastically reduce HBsAg levels (PubMed: 36350150). This reduction is intended to relieve immune suppression, potentially allowing the host's immune system to re-engage and achieve a functional cure, characterized by sustained HBsAg loss (PubMed: 33186511). Current clinical candidates like Bepirovirsen and JNJ-3989 targeting this RNA have shown significant efficacy in lowering viral proteins in clinical trials (GSK, Janssen). The therapeutic strategy involves the degradation of the RNA before it can be translated, thereby cutting off the supply of HBsAg at the source. This approach differs from traditional nucleos(t)ide analogs, which primarily inhibit DNA synthesis but have little effect on HBsAg production. Monitoring of serum HBsAg levels serves as a key indicator of the drug's pharmacodynamic effect. Successful suppression of this target is considered a prerequisite for achieving long-term remission in patients with chronic hepatitis B.

Other names

HBsAg mRNAHBV 2.1 kb transcriptHepatitis B virus S-gene transcriptHBV surface antigen RNA

Degradation of viral mRNA via RNA interference (siRNA) or RNase H-mediated cleavage (antisense oligonucleotides), resulting in the suppression of HBsAg production (PubMed: 34161727).