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Front Immunol. 2018 Sep 11;9:2080. doi: 10.3389/fimmu.2018.02080. eCollection 2018.
Inhibition of HBV Expression in HBV Transgenic Mice Using AAV-Delivered CRISPR-SaCas9.
Li H1,2, Sheng C1, Liu H1, Wang S1, Zhao J1, Yang L1, Jia L1, Li P1, Wang L1, Xie J1, Xu D3, Sun Y2, Qiu S1, Song H1.
Author information
1
Institute of Disease Control and Prevention, Academy of Military Medical Sciences, Beijing, China.
2
State Key Laboratory of Pathogen and Biosecurity, Academy of Military Medical Sciences, Beijing, China.
3
Research Centre for Liver Failure, Beijing 302nd Hospital, Beijing, China.
Abstract
The chronic production of hepatitis B viral (HBV) antigens could cause inflammation and necrosis, leading to elevation of liver enzymes from necrotic hepatocytes, hepatitis, cirrhosis, hepatocellular carcinoma, and liver failure. However, no current treatment is capable of significantly reducing HBsAg expression in patients. Our previous studies had confirmed the ability of CRISPR-Cas9 in disrupting HBV cccDNA. Here, to inhibit HBV expression efficiently in the mouse model of chronic HBV infection, the miniaturized CRISPR-SaCas9 system compatible with a HBV core region derived guide-RNA had been packaged in recombinant adeno-associated virus (AAV) type 8, which lowered the levels of serum HBsAg, HBeAg, and HBV DNA efficiently in HBV transgenic mice during 58 days continuous observation after vein injection. It further confirms the potential of the CRISPR-Cas9 technique for use in hepatitis B gene therapy.
KEYWORDS:
CRISPR-SaCas9; HBV; HBsAg; adeno-associated virus; gene therapy
PMID:
30254645
PMCID:
PMC6141737
DOI:
10.3389/fimmu.2018.02080
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发表于 2018-9-27 20:42
