title: Inhibition of hepatitis B virus by the CRISPR/Cas9 system via targeting the conserved regions of the viral genome.
abstract: Hepatitis B virus (HBV) remains a global health threat as chronic HBV infection may lead to liver cirrhosis or cancer. Current antiviral therapies with nucleoside analogues can inhibit the replication of HBV, but do not disrupt the already existing HBV covalently closed circular DNA. The newly developed CRISPR (clustered regularly interspaced short palindromic repeats)/Cas9 (CRISPR-associated 9) system is a powerful tool to target cellular genome DNA for gene editing. In order to investigate the possibility of using the CRISPR/Cas9 system to disrupt the HBV DNA templates, we designed eight guide RNAs (gRNAs) that targeted the conserved regions of different HBV genotypes, which could significantly inhibit HBV replication both in vitro and in vivo. Moreover, the HBV-specific gRNA/Cas9 system could inhibit the replication of HBV of different genotypes in cells, and the viral DNA was significantly reduced by a single gRNA/Cas9 system and cleared by a combination of different gRNA/Cas9 systems.
authors.affiliation: State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, Hubei, 430072, PR China.
authors.forename: Xing
authors.initials: X
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, Hubei, 430072, PR China.
authors.forename: Ruidong
authors.initials: R
authors.lastname: Hao
authors.affiliation: School of Basic Medical Sciences, Wuhan University, Wuhan, Hubei, 430072, PR China.
authors.forename: Shuliang
authors.initials: S
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, Hubei, 430072, PR China.|School of Basic Medical Sciences, Wuhan University, Wuhan, Hubei, 430072, PR China.
authors.forename: Deyin
authors.initials: D
authors.lastname: Guo
authors.affiliation: State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, Hubei, 430072, PR China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Chen
mesh_terms: D000818:Animals; D001483:Base Sequence; D064113:CRISPR-Cas Systems; D064112:Clustered Regularly Interspaced Short Palindromic Repeats; D017124:Conserved Sequence; D018390:Gene Targeting / Q000379:methods; D016679:Genome, Viral; D006509:Hepatitis B / Q000821:virology*; D006515:Hepatitis B virus / Q000235:genetics* / Q000502:physiology; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D014779:Virus Replication