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

被引：119
作者：
Martinez, Maria Guadalupe [1 ]
Boyd, Anders [2 ,3 ]
Combe, Emmanuel [1 ]
Testoni, Barbara [1 ]
Zoulim, Fabien [1 ,4 ,5 ]
机构：
[1] Canc Res Ctr Lyon CRCL, CNRS UMR 5286, INSERM U1052, F-69008 Lyon, France
[2] Stichting HIV Monitoring, Amsterdam, Netherlands
[3] Publ Hlth Serv Amsterdam, Dept Infect Dis Res & Prevent, Amsterdam, Netherlands
[4] Univ Claude Bernard UCBL, Univ Lyon, F-69008 Lyon, France
[5] Hosp Civils Lyon HCL, F-69002 Lyon, France
来源：
JOURNAL OF HEPATOLOGY | 2021年 / 75卷 / 03期
关键词：
HEPATITIS-B-VIRUS; X PROTEIN; IN-VITRO; EPIGENETIC REGULATION; TENOFOVIR DISOPROXIL; REPLICATIVE ACTIVITY; HEPATOCYTE TURNOVER; ANTIVIRAL ACTIVITY; CCCDNA; INHIBITION;
D O I：
10.1016/j.jhep.2021.05.013
中图分类号：
R57 [消化系及腹部疾病];
学科分类号：
摘要：
Current antiviral therapies, such as pegylated interferon-a 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. (c) 2021 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
引用
收藏
页码：706 / 717
页数：12
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