Open Access

Scientific Reports, volume 9, issue 1, publication number 1847

Suppressing the NHEJ pathway by DNA-PKcs inhibitor NU7026 prevents degradation of HBV cccDNA cleaved by CRISPR/Cas9

Kostyushev Dmitry ¹

Kostyusheva Anastasiya ¹

Brezgin Sergey ^{1, 2}

Zarifyan Dmitry ¹

Utkina Anastasiya ¹

Goptar Irina ^{1, 3}

Chulanov Vladimir ^{1, 4}

Hide authors affiliations Show authors affiliations: 4 affiliations

Central Research Institute of Epidemiology, Viral Hepatitis, Moscow, Russian Federation |

Institute of Immunology, Federal Medical Biological Agency, Moscow, Russian Federation |

Izmerov Research Institute of Occupational Health, Gene Engineering and Biotechnology, Moscow, Russian Federation |

⁴

I.M. Sechenov First Moscow State Medical University, Infectious Diseases, Moscow, Russian Federation |

Publication type: Journal Article

Publication date: 2019-02-12

Springer Nature

Journal: Scientific Reports

Quartile SCImago

Quartile WOS

Impact factor: 4.6

ISSN: 20452322

DOI: 10.1038/s41598-019-38526-6

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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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Citations by journals

	1 2 3 4
International Journal of Molecular Sciences	International Journal of Molecular Sciences, 4, 11.43% International Journal of Molecular Sciences 4 publications, 11.43%
Viruses	Viruses, 3, 8.57% Viruses 3 publications, 8.57%
Microorganisms	Microorganisms, 2, 5.71% Microorganisms 2 publications, 5.71%
Molecular Biology	Molecular Biology, 2, 5.71% Molecular Biology 2 publications, 5.71%
Frontiers in Genetics	Frontiers in Genetics, 2, 5.71% Frontiers in Genetics 2 publications, 5.71%
Molecular Therapy - Nucleic Acids	Molecular Therapy - Nucleic Acids, 2, 5.71% Molecular Therapy - Nucleic Acids 2 publications, 5.71%
Nucleic Acid Therapeutics	Nucleic Acid Therapeutics, 1, 2.86% Nucleic Acid Therapeutics 1 publication, 2.86%
Hepatology Communications	Hepatology Communications, 1, 2.86% Hepatology Communications 1 publication, 2.86%
Journal of Clinical Medicine	Journal of Clinical Medicine, 1, 2.86% Journal of Clinical Medicine 1 publication, 2.86%
Genes	Genes, 1, 2.86% Genes 1 publication, 2.86%
Frontiers in Cellular and Infection Microbiology	Frontiers in Cellular and Infection Microbiology, 1, 2.86% Frontiers in Cellular and Infection Microbiology 1 publication, 2.86%
Cellular and Molecular Biology Letters	Cellular and Molecular Biology Letters, 1, 2.86% Cellular and Molecular Biology Letters 1 publication, 2.86%
Oncogene	Oncogene, 1, 2.86% Oncogene 1 publication, 2.86%
Biomedicine and Pharmacotherapy	Biomedicine and Pharmacotherapy, 1, 2.86% Biomedicine and Pharmacotherapy 1 publication, 2.86%
BioImpacts	BioImpacts, 1, 2.86% BioImpacts 1 publication, 2.86%
Molecular Immunology	Molecular Immunology, 1, 2.86% Molecular Immunology 1 publication, 2.86%
IUBMB Life	IUBMB Life, 1, 2.86% IUBMB Life 1 publication, 2.86%
Cell Biochemistry and Function	Cell Biochemistry and Function, 1, 2.86% Cell Biochemistry and Function 1 publication, 2.86%
Immunity, inflammation and disease	Immunity, inflammation and disease, 1, 2.86% Immunity, inflammation and disease 1 publication, 2.86%
Expert Opinion on Therapeutic Targets	Expert Opinion on Therapeutic Targets, 1, 2.86% Expert Opinion on Therapeutic Targets 1 publication, 2.86%
Virulence	Virulence, 1, 2.86% Virulence 1 publication, 2.86%
Progress in Molecular Biology and Translational Science	Progress in Molecular Biology and Translational Science, 1, 2.86% Progress in Molecular Biology and Translational Science 1 publication, 2.86%
Advances in Experimental Medicine and Biology	Advances in Experimental Medicine and Biology, 1, 2.86% Advances in Experimental Medicine and Biology 1 publication, 2.86%
World Journal of Hepatology	World Journal of Hepatology, 1, 2.86% World Journal of Hepatology 1 publication, 2.86%
Clinics in Liver Disease	Clinics in Liver Disease, 1, 2.86% Clinics in Liver Disease 1 publication, 2.86%
Current Molecular Medicine	Current Molecular Medicine, 1, 2.86% Current Molecular Medicine 1 publication, 2.86%
	1 2 3 4

Citations by publishers

	2 4 6 8 10 12
Multidisciplinary Digital Publishing Institute (MDPI)	Multidisciplinary Digital Publishing Institute (MDPI), 11, 31.43% Multidisciplinary Digital Publishing Institute (MDPI) 11 publications, 31.43%
Elsevier	Elsevier, 6, 17.14% Elsevier 6 publications, 17.14%
Wiley	Wiley, 4, 11.43% Wiley 4 publications, 11.43%
Frontiers Media S.A.	Frontiers Media S.A., 3, 8.57% Frontiers Media S.A. 3 publications, 8.57%
Springer Nature	Springer Nature, 3, 8.57% Springer Nature 3 publications, 8.57%
Pleiades Publishing	Pleiades Publishing, 2, 5.71% Pleiades Publishing 2 publications, 5.71%
Taylor & Francis	Taylor & Francis, 2, 5.71% Taylor & Francis 2 publications, 5.71%
Mary Ann Liebert	Mary Ann Liebert, 1, 2.86% Mary Ann Liebert 1 publication, 2.86%
Maad Rayan Publishing Company	Maad Rayan Publishing Company, 1, 2.86% Maad Rayan Publishing Company 1 publication, 2.86%
Baishideng Publishing Group	Baishideng Publishing Group, 1, 2.86% Baishideng Publishing Group 1 publication, 2.86%
Bentham Science	Bentham Science, 1, 2.86% Bentham Science 1 publication, 2.86%
	2 4 6 8 10 12

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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

GOST all authors (up to 50) Copy

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

RIS |

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RIS Copy

TY - JOUR

DO - 10.1038/s41598-019-38526-6

UR - https://doi.org/10.1038%2Fs41598-019-38526-6

TI - Suppressing the NHEJ pathway by DNA-PKcs inhibitor NU7026 prevents degradation of HBV cccDNA cleaved by CRISPR/Cas9

T2 - Scientific Reports

AU - Kostyusheva, Anastasiya

AU - Zarifyan, Dmitry

AU - Utkina, Anastasiya

AU - Goptar, Irina

AU - Chulanov, Vladimir

AU - Kostyushev, Dmitry

AU - Brezgin, Sergey

PY - 2019

DA - 2019/02/12 00:00:00

PB - Springer Nature

IS - 1

VL - 9

PMID - 30755668

SN - 2045-2322

ER -

BibTex

Cite this

BibTex Copy

@article{2019_Kostyushev,

author = {Anastasiya Kostyusheva and Dmitry Zarifyan and Anastasiya Utkina and Irina Goptar and Vladimir Chulanov and Dmitry Kostyushev and Sergey Brezgin},

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%2Fs41598-019-38526-6},

number = {1},

doi = {10.1038/s41598-019-38526-6}

}

Found error?

Publisher

Springer Nature

Journal

Scientific Reports

Quartile SCImago

Quartile WOS

Impact factor

4.6

ISSN

20452322 (Print)

Labs

Laboratory of Genetic Technologies

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