Open Access
International Journal of Molecular Sciences, volume 21, issue 18, pages 6865
Clearing of Foreign Episomal DNA from Human Cells by CRISPRa-Mediated Activation of Cytidine Deaminases
Brezgin Sergey
1, 2
,
Ponomareva Natalia
1
,
Volia Viktoriia
1
,
Goptar Irina
3
,
Nikiforova Anastasiya
3
,
Shilovskiy Igor
2
,
Smirnov Valery
2
,
Chulanov Vladimir
1, 4
1
Department of Molecular Biology and Immunopathology of Infectious Diseases, National Medical Research Center for Tuberculosis and Infectious Diseases, 127994 Moscow, Russia
|
Publication type: Journal Article
Publication date: 2020-09-18
Quartile SCImago
Q1
Quartile WOS
Q1
Impact factor: 5.6
ISSN: 16616596, 14220067
PubMed ID:
32962129
Catalysis
Organic Chemistry
Inorganic Chemistry
Physical and Theoretical Chemistry
Computer Science Applications
Spectroscopy
Molecular Biology
General Medicine
Abstract
Restriction of foreign DNA is a fundamental defense mechanism required for maintaining genomic stability and proper function of mammalian cells. APOBEC cytidine deaminases are crucial effector molecules involved in clearing pathogenic DNA of viruses and other microorganisms and improperly localized self-DNA (DNA leakages). Mastering the expression of APOBEC provides the crucial means both for developing novel therapeutic approaches for combating infectious and non-infectious diseases and for numerous research purposes. In this study, we report successful application of a CRISPRa approach to effectively and specifically overexpress APOBEC3A and APOBEC3B deaminases and describe their effects on episomal and integrated foreign DNA. This method increased target gene transcription by >6–50-fold in HEK293T cells. Furthermore, CRISPRa-mediated activation of APOBEC3A/APOBEC3B suppressed episomal but not integrated foreign DNA. Episomal GC-rich DNA was rapidly destabilized and destroyed by CRISPRa-induced APOBEC3A/APOBEC3B, while the remaining DNA templates harbored frequent deaminated nucleotides. To conclude, the CRISPRa approach could be readily utilized for manipulating innate immunity and investigating the effects of the key effector molecules on foreign nucleic acids.
Citations by journals
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1
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Methods
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Methods
1 publication, 20%
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Viruses
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Viruses
1 publication, 20%
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Nucleic Acid Therapeutics
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Nucleic Acid Therapeutics
1 publication, 20%
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Biochemistry (Moscow)
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Biochemistry (Moscow)
1 publication, 20%
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Molecular Biology
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Molecular Biology
1 publication, 20%
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1
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Citations by publishers
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1
2
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Pleiades Publishing
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Pleiades Publishing
2 publications, 40%
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Elsevier
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Elsevier
1 publication, 20%
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Multidisciplinary Digital Publishing Institute (MDPI)
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Multidisciplinary Digital Publishing Institute (MDPI)
1 publication, 20%
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Mary Ann Liebert
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Mary Ann Liebert
1 publication, 20%
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1
2
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- We do not take into account publications that without a DOI.
- Statistics recalculated only for publications connected to researchers, organizations and labs registered on the platform.
- Statistics recalculated weekly.
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Brezgin S. et al. Clearing of Foreign Episomal DNA from Human Cells by CRISPRa-Mediated Activation of Cytidine Deaminases // International Journal of Molecular Sciences. 2020. Vol. 21. No. 18. p. 6865.
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Brezgin S., Kostyusheva A., Ponomareva N., Volia V., Goptar I., Nikiforova A., Shilovskiy I., Smirnov V., Kostyushev D., Chulanov V. Clearing of Foreign Episomal DNA from Human Cells by CRISPRa-Mediated Activation of Cytidine Deaminases // International Journal of Molecular Sciences. 2020. Vol. 21. No. 18. p. 6865.
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TY - JOUR
DO - 10.3390/ijms21186865
UR - https://doi.org/10.3390%2Fijms21186865
TI - Clearing of Foreign Episomal DNA from Human Cells by CRISPRa-Mediated Activation of Cytidine Deaminases
T2 - International Journal of Molecular Sciences
AU - Brezgin, Sergey
AU - Kostyusheva, Anastasiya
AU - Ponomareva, Natalia
AU - Volia, Viktoriia
AU - Goptar, Irina
AU - Nikiforova, Anastasiya
AU - Shilovskiy, Igor
AU - Smirnov, Valery
AU - Kostyushev, Dmitry
AU - Chulanov, Vladimir
PY - 2020
DA - 2020/09/18 00:00:00
PB - Multidisciplinary Digital Publishing Institute (MDPI)
SP - 6865
IS - 18
VL - 21
PMID - 32962129
SN - 1661-6596
SN - 1422-0067
ER -
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@article{2020_Brezgin,
author = {Sergey Brezgin and Anastasiya Kostyusheva and Natalia Ponomareva and Viktoriia Volia and Irina Goptar and Anastasiya Nikiforova and Igor Shilovskiy and Valery Smirnov and Dmitry Kostyushev and Vladimir Chulanov},
title = {Clearing of Foreign Episomal DNA from Human Cells by CRISPRa-Mediated Activation of Cytidine Deaminases},
journal = {International Journal of Molecular Sciences},
year = {2020},
volume = {21},
publisher = {Multidisciplinary Digital Publishing Institute (MDPI)},
month = {sep},
url = {https://doi.org/10.3390%2Fijms21186865},
number = {18},
pages = {6865},
doi = {10.3390/ijms21186865}
}
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MLA
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Brezgin, Sergey, et al. “Clearing of Foreign Episomal DNA from Human Cells by CRISPRa-Mediated Activation of Cytidine Deaminases.” International Journal of Molecular Sciences, vol. 21, no. 18, Sep. 2020, p. 6865. https://doi.org/10.3390%2Fijms21186865.