Open Access
Suppressing the NHEJ pathway by DNA-PKcs inhibitor NU7026 prevents degradation of HBV cccDNA cleaved by CRISPR/Cas9
Sergey Brezgin
1, 2
,
Dmitry Zarifyan
1
,
Anastasiya Utkina
1
,
Irina Goptar
1, 3
,
Vladimir Chulanov
1, 4
Publication type: Journal Article
Publication date: 2019-02-12
scimago Q1
wos Q1
SJR: 0.874
CiteScore: 6.7
Impact factor: 3.9
ISSN: 20452322
PubMed ID:
30755668
Multidisciplinary
Abstract
Chronic hepatitis B is a severe liver disease caused by hepatitis B virus (HBV) infection. Covalently closed circular DNA (cccDNA), a super-spiralized, double-stranded form of the HBV genome, is the major determinant of viral persistence. CRISPR/Cas9 nucleases have been recently shown to introduce double-stranded DNA breaks into HBV cccDNA. The inflicted damage results predominantly in erroneous repair of cccDNA by non-homologous end-joining (NHEJ). NHEJ has been suggested to enhance anti-HBV activity of CRISPR/Cas9 and increase cccDNA mutation. In this study, we assessed anti-HBV activity of CRISPR/Cas9 and cccDNA repair outcomes in an altered NHEJ/HR environment. NU7026, a strong inhibitor of NHEJ, prevented CRISPR/Cas9-mediated degradation of cccDNA and resulted in frequent on-target deletions. We conclude that CRISPR/Cas9 is a highly effective tool to degrade cccDNA and first demonstrate that inhibiting NHEJ impairs cccDNA degradation.
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46
Total citations:
46
Citations from 2024:
12
(26%)
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GOST
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Kostyushev D. et al. Suppressing the NHEJ pathway by DNA-PKcs inhibitor NU7026 prevents degradation of HBV cccDNA cleaved by CRISPR/Cas9 // Scientific Reports. 2019. Vol. 9. No. 1. 1847
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Kostyushev D., Kostyusheva A., Brezgin S., Zarifyan D., Utkina A., Goptar I., Chulanov V. Suppressing the NHEJ pathway by DNA-PKcs inhibitor NU7026 prevents degradation of HBV cccDNA cleaved by CRISPR/Cas9 // Scientific Reports. 2019. Vol. 9. No. 1. 1847
Cite this
RIS
Copy
TY - JOUR
DO - 10.1038/s41598-019-38526-6
UR - https://doi.org/10.1038/s41598-019-38526-6
TI - Suppressing the NHEJ pathway by DNA-PKcs inhibitor NU7026 prevents degradation of HBV cccDNA cleaved by CRISPR/Cas9
T2 - Scientific Reports
AU - Kostyushev, Dmitry
AU - Kostyusheva, Anastasiya
AU - Brezgin, Sergey
AU - Zarifyan, Dmitry
AU - Utkina, Anastasiya
AU - Goptar, Irina
AU - Chulanov, Vladimir
PY - 2019
DA - 2019/02/12
PB - Springer Nature
IS - 1
VL - 9
PMID - 30755668
SN - 2045-2322
ER -
Cite this
BibTex (up to 50 authors)
Copy
@article{2019_Kostyushev,
author = {Dmitry Kostyushev and Anastasiya Kostyusheva and Sergey Brezgin and Dmitry Zarifyan and Anastasiya Utkina and Irina Goptar and Vladimir Chulanov},
title = {Suppressing the NHEJ pathway by DNA-PKcs inhibitor NU7026 prevents degradation of HBV cccDNA cleaved by CRISPR/Cas9},
journal = {Scientific Reports},
year = {2019},
volume = {9},
publisher = {Springer Nature},
month = {feb},
url = {https://doi.org/10.1038/s41598-019-38526-6},
number = {1},
pages = {1847},
doi = {10.1038/s41598-019-38526-6}
}