CRISPR-Cas9 gene editing of hepatitis B virus in chronically infected humanized mice.

ABSTRACT: Chronic hepatitis B virus (HBV) infection is a major public health problem. New treatment approaches are needed because current treatments do not target covalently closed circular DNA (cccDNA), the template for HBV replication, and rarely clear the virus. We harnessed adeno-associated virus (AAV) vectors and CRISPR-Staphylococcus aureus (Sa)Cas9 to edit the HBV genome in liver-humanized FRG mice chronically infected with HBV and receiving entecavir. Gene editing was detected in livers of five of eight HBV-specific AAV-SaCas9-treated mice, but not control mice, and mice with detectable HBV gene editing showed higher levels of SaCas9 delivery to HBV⁺ human hepatocytes than those without gene editing. HBV-specific AAV-SaCas9 therapy significantly

SUBMITTER: Stone D 

PROVIDER: S-EPMC7803634 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature