Hepatitis B virus covalently closed circular DNA and integrated DNA (HBV cccDNA and integrated HBV DNA)

**Hepatitis B virus covalently closed circular DNA (cccDNA)** is the stable, episomal form of the viral genome within the nucleus of infected hepatocytes, serving as the essential template for all viral transcripts and persistence of infection[1][3][9]. **Integrated HBV DNA** refers to linear HBV DNA sequences that are incorporated into the host cell genome, a process that occurs early and throughout chronic infection, and is implicated in hepatocellular carcinoma (HCC) development due to disruption of host genes and insertional mutagenesis[2][4][8]. Both cccDNA and integrated DNA are not targeted by current antiviral drugs, forming a reservoir for viral persistence—cccDNA for active replication and integrated DNA for ongoing antigen (HBsAg) production as well as carcinogenesis[1][2][7][8][9]. These viral DNA forms are *nucleic acid-based therapeutic targets* rather than proteins, making their elimination a major focus of research into curative HBV therapies. Emerging approaches target either cccDNA transcriptional silencing, direct elimination, or gene editing of integrated HBV DNA, but clinical implementation is limited by safety and technical challenges.

Other names

cccDNAintegrated HBV DNAHBV episomal DNAHBV integrated DNA

Inhibition of viral replication (by affecting reverse transcription, limiting DNA available to form cccDNA; nucleos(t)ide analogues); Inhibition of cccDNA transcription (epigenetic silencing); Direct cleavage/disruption of cccDNA or integrated DNA (gene editing approaches such as CRISPR/Cas9, TALENs); Degradation/removal of cccDNA (experimental)