Hepatitis B virus covalently closed circular DNA-derived RNA transcripts (HBV cccDNA-derived RNA)

Hepatitis B virus (HBV) covalently closed circular DNA (cccDNA)-derived RNA transcripts are the essential intermediary molecules in the HBV life cycle, produced from the stable cccDNA reservoir in the nucleus of infected hepatocytes (Source: PubMed, PMID: 32659301). These transcripts include the 3.5kb pregenomic RNA (pgRNA), which serves as the template for reverse transcription into new viral DNA, and various subgenomic RNAs (2.4kb, 2.1kb, and 0.7kb) that encode viral proteins such as HBsAg, HBeAg, and the X protein (Source: Journal of Hepatology, doi:10.1016/j.jhep.2020.11.036). Because current nucleos(t)ide analogs only inhibit DNA synthesis and do not eliminate cccDNA or its RNA products, these transcripts have become a primary therapeutic target for achieving a functional cure (Source: NIH, National Institute of Allergy and Infectious Diseases). Therapeutic agents like antisense oligonucleotides (ASOs) and small interfering RNAs (siRNAs) are designed to bind and trigger the degradation of these transcripts, thereby reducing viral replication and the expression of immunosuppressive viral antigens (Source: GSK, Bepirovirsen clinical data). This reduction is intended to alleviate the exhaustion of the host immune system and facilitate the clearance of infected cells (Source: Vir Biotechnology, VIR-2218 pipeline). By targeting the RNA directly, these therapies can simultaneously lower HBsAg levels and inhibit the production of new viral particles, addressing a major hurdle in the treatment of chronic hepatitis B (Source: PubMed, PMID: 33217442).

Other names

HBV RNAPregenomic RNApgRNASubgenomic HBV RNAHBV messenger RNAHBV transcripts

Degradation of viral RNA transcripts via RNA interference (siRNA) or antisense oligonucleotides (ASO) to inhibit viral protein synthesis and replication.