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Abstract Details
Covalently closed circular DNA: the ultimate therapeutic target for curing Hepatitis B virus infections
J Hepatol. 2021 May 26;S0168-8278(21)00348-2. doi: 10.1016/j.jhep.2021.05.013.Online ahead of print.
Maria Guadalupe Martinez1, Anders Boyd2, Emmanuel Combe1, Barbara Testoni1, Fabien Zoulim3
Author information
1INSERM U1052, CNRS UMR-5286, Cancer Research Center of Lyon (CRCL), Lyon, 69008, France.
2Stichting HIV Monitoring, Amsterdam, the Netherlands; Department of Infectious Diseases, Research and Prevention, Public Health Service of Amsterdam, Amsterdam, the Netherlands.
3INSERM U1052, CNRS UMR-5286, Cancer Research Center of Lyon (CRCL), Lyon, 69008, France; University of Lyon, Université Claude- Bernard (UCBL), 69008 Lyon, France; Hospices Civils de Lyon (HCL), 69002 Lyon, France. Electronic address: fabien.zoulim@inserm.fr.
Abstract
Current antiviral therapies, such as pegylated interferon alpha and nucleos(t)ide analogs effectively improve the patient's quality of life. However, they are limited to control the infection but cannot cure infected hepatocytes. Complete HBV cure is hampered due to the lack of therapies that can directly affect the viral minichromosome, covalently closed circular DNA. Efforts currently in the pipeline for early clinical trials aim to achieve a functional cure, defined by the loss of Hepatitis B surface antigen and undetectable HBV DNA levels in serum. However, achieving a complete HBV cure requires therapies that can directly affect the cccDNA pool, either for its degradation, lethal mutations or functional silencing. In this review we discuss cutting-edge technologies that could lead to non-cytolytic direct cccDNA targeting, curing infected hepatocytes.