Covalently closed circular DNA: The ultimate therapeutic target for curing HBV infections

Maria Guadalupe Martinez, Anders Boyd, Emmanuel Combe, Barbara Testoni, Fabien Zoulim

Research output: Contribution to journalReview articleAcademicpeer-review

50 Citations (Scopus)

Abstract

Current antiviral therapies, such as pegylated interferon-α and nucleos(t)ide analogues, effectively improve the quality of life of patients with chronic hepatitis B. However, they can only control the infection rather than curing infected hepatocytes. Complete HBV cure is hampered by the lack of therapies that can directly affect the viral minichromosome (in the form of covalently closed circular DNA [cccDNA]). Approaches currently under investigation in early clinical trials are aimed at achieving a functional cure, defined as the loss of HBsAg and undetectable HBV DNA levels in serum. However, achieving a complete HBV cure requires therapies that can directly target the cccDNA pool, either via degradation, lethal mutations or functional silencing. In this review, we discuss cutting-edge technologies that could lead to non-cytolytic direct cccDNA targeting and cure of infected hepatocytes.

Original languageEnglish
Pages (from-to)706-717
Number of pages12
JournalJournal of Hepatology
Volume75
Issue number3
DOIs
Publication statusPublished - Sept 2021

Keywords

  • HBV cure
  • cccDNA
  • chronic hepatitis B
  • direct-acting antivirals

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