[CRISPR/Cas9 核糖核蛋白複合物對體內乙型肝炎病毒模型的抗病毒活性]
[俄語文章]
A P Kostyusheva 1 , S A Brezgin 1 2 , N I Ponomareva 1 2 , I A Goptar 3 , A V Nikiforova 3 , V I Gegechkori 1 , V B Poluektova 1 , K A Turkadze 1 , A E Sudina 4 , V P Chulanov 1 2 4 , D S 2 Kostyushev 1
隸屬關係
[Antiviral Activity of CRISPR/Cas9 Ribonucleoprotein Complexes on a Hepatitis B Virus Model In Vivo]
[Article in Russian]
A P Kostyusheva 1 , S A Brezgin 1 2 , N I Ponomareva 1 2 , I A Goptar 3 , A V Nikiforova 3 , V I Gegechkori 1 , V B Poluektova 1 , K A Turkadze 1 , A E Sudina 4 , V P Chulanov 1 2 4 , D S Kostyushev 1 2 5
Affiliations
PMID: 36475475 DOI: 10.31857/S002689842206012X
Abstract
Chronic hepatitis B (CHB) is caused by hepatitis B virus (HBV) infection. This disease is a key issue for global health. Modern methods of therapy do not completely eliminate HBV from infected cells and do not cure chronic infection. The CRISPR/Cas9 systems of site-specific nucleases can effectively cleave do not target DNA including viral genomes. The cleavage of the major form of the HBV genome, i.e., covalently closed circular DNA (cccDNA), leads to a robust reduction in viral replication and degradation or mutational inactivation of cccDNA. CRISPR/Cas9-based approaches are one of the most promising ways to achieve a 'sterilizing' cure of CHB, i.e., complete elimination of the virus from the body. Here, the HBV mouse model in vivo has been used to analyze the antiviral activity of the high-specific Cas9 protein and sgRNA targeting HBV genome. We have found that a single injection of short-lived ribonucleoprotein complexes of CRISPR/Cas9 results in a ~10-fold reduction in HBV DNA levels in the serum and liver of mice as early as 48 h after the start of the experiment. The remaining HBV DNAs have been found to harbor rare indel mutations. Developing new antivirals for treating CHB based on CRISPR/Cas9 ribonucleoprotein complexes could substantially reduce the duration of CHB therapy and, potentially, achieve complete elimination of viral infection.