TY - JOUR
T1 - Covalently closed circular DNA
T2 - The ultimate therapeutic target for curing HBV infections
AU - Martinez, Maria Guadalupe
AU - Boyd, Anders
AU - Combe, Emmanuel
AU - Testoni, Barbara
AU - Zoulim, Fabien
N1 - Funding Information: This work was funded by the University of Lyon “Excellence laboratories” grant (Labex DevWeCan n° ANR-10-LABX-61) and Agence Nationale de Recherches sur le SIDA et les hepatites virales (ANRS) to FZ and BT paid to their institution. AB received grants from the ANRS and Sidaction , paid to his institution. Funding Information: This work was funded by the University of Lyon ?Excellence laboratories? grant (Labex DevWeCan n? ANR-10-LABX-61) and Agence Nationale de Recherches sur le SIDA et les hepatites virales (ANRS) to FZ and BT paid to their institution. AB received grants from the ANRS and Sidaction, paid to his institution. Publisher Copyright: © 2021 European Association for the Study of the Liver
PY - 2021/9
Y1 - 2021/9
N2 - 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.
AB - 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.
KW - HBV cure
KW - cccDNA
KW - chronic hepatitis B
KW - direct-acting antivirals
UR - http://www.scopus.com/inward/record.url?scp=85109109946&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/j.jhep.2021.05.013
DO - https://doi.org/10.1016/j.jhep.2021.05.013
M3 - Review article
C2 - 34051332
SN - 0168-8278
VL - 75
SP - 706
EP - 717
JO - Journal of Hepatology
JF - Journal of Hepatology
IS - 3
ER -