Hepatitis B virus S region messenger RNA (HBV S mRNA) (HBV S mRNA)

The Hepatitis B virus (HBV) S region messenger RNA (mRNA) is a vital viral transcript responsible for encoding the Hepatitis B surface antigens (HBsAg), including the Large, Middle, and Small surface proteins (PMID: 33164343). These proteins are crucial for the assembly of the viral envelope and the secretion of subviral particles that overwhelm the host immune system (PubMed: 31536350). In chronic HBV infection, the persistent expression of HBsAg leads to T-cell exhaustion and immune tolerance, preventing viral clearance (NIH: PMC7074462). Therapeutic strategies targeting the S region mRNA, such as antisense oligonucleotides (ASOs) and small interfering RNAs (siRNAs), utilize the overlapping nature of the HBV genome to degrade multiple viral transcripts simultaneously (NEJM: 10.1056/NEJMoa2210027). This approach aims to achieve a functional cure by significantly reducing HBsAg levels and restoring the patient's innate and adaptive immune responses (Nature Reviews: 10.1038/s41575-020-0332-6). Several clinical-stage candidates, including Bepirovirsen and JNJ-3989, have shown efficacy in reducing viral markers in patients with chronic hepatitis B (GSK, 2022; Arrowhead Pharmaceuticals, 2023).

Other names

Hepatitis B virus surface antigen mRNAHBsAg mRNAHBV S-gene transcriptHBV S-region RNAHBV surface region mRNAHBV S-region mRNA

Drugs targeting the HBV S region mRNA primarily utilize RNA interference (RNAi) or antisense technology. Small interfering RNAs (siRNAs) like JNJ-3989 and VIR-2218 are loaded into the RNA-induced silencing complex (RISC) to catalyze the sequence-specific cleavage of the mRNA (PubMed: 31536350). Antisense oligonucleotides (ASOs) like Bepirovirsen bind to the target mRNA and recruit RNase H to degrade the RNA-DNA heteroduplex (NEJM: 10.1056/NEJMoa2210027). Because the HBV genome consists of overlapping open reading frames, targeting the S region often results in the degradation of all major HBV RNA species, leading to a broad reduction in viral proteins and DNA (Nature Reviews: 10.1038/s41575-020-0332-6).