Depleting hepatitis B virus relaxed circular DNA is necessary for resolution of infection by CRISPR-Cas9

Kostyushev, D.; Kostyusheva, A.; Brezgin, S.; Ponomareva, N.; Zakirova, N.F.; Egorshina, A.; Yanvarev, D.V.; Bayurova, E.; Sudina, A.; Goptar, I.; Nikiforova, A.; Dunaeva, E.; Lisitsa, T.; Abramov, I.; Frolova, A.; Lukashev, A.; Gordeychuk, I.; Zamyatnin, A.A.; Ivanov, A.; Chulanov, V.

Статья опубликована в высокорейтинговом журнале

Информация о цитировании статьи получена из Scopus
Статья опубликована в журнале из списка Web of Science и/или Scopus
Дата последнего поиска статьи во внешних источниках: 31 июля 2024 г.

Авторы: Kostyushev Dmitry, Kostyusheva Anastasiya, Brezgin Sergey, Ponomareva Natalia, Zakirova Natalia F., Egorshina Aleksandra, Yanvarev Dmitry V., Bayurova Ekaterina, Sudina Anna, Goptar Irina, Nikiforova Anastasiya, Dunaeva Elena, Lisitsa Tatiana, Abramov Ivan, Frolova Anastasiia, Lukashev Alexander, Gordeychuk Ilya, Zamyatnin Andrey A., Ivanov Alexander, Chulanov Vladimir
Журнал: Molecular therapy. Nucleic acids
Том: 31
Год издания: 2023
Издательство: Nature Publishing Group
Местоположение издательства: United Kingdom
Первая страница: 482
Последняя страница: 493
DOI: 10.1016/j.omtn.2023.02.001
Аннотация: CRISPR-Cas9 systems can directly target the hepatitis B virus (HBV) major genomic form, covalently closed circular DNA (cccDNA), for decay and demonstrate remarkable anti-HBV activity. Here, we demonstrate that CRISPR-Cas9-mediated inactivation of HBV cccDNA, frequently regarded as the “holy grail” of viral persistence, is not sufficient for curing infection. Instead, HBV replication rapidly rebounds because of de novo formation of HBV cccDNA from its precursor, HBV relaxed circular DNA (rcDNA). However, depleting HBV rcDNA before CRISPR-Cas9 ribonucleoprotein (RNP) delivery prevents viral rebound and promotes resolution of HBV infection. These findings provide the groundwork for developing approaches for a virological cure of HBV infection by a single dose of short-lived CRISPR-Cas9 RNPs. Blocking cccDNA replenishment and re-establishment from rcDNA conversion is critical for completely clearing the virus from infected cells by site-specific nucleases. The latter can be achieved by widely used reverse transcriptase inhibitors.
Добавил в систему: Замятнин Андрей Александрович

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