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Harnessing the clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated Cas9 system to disrupt the hepatitis B virus

Zhen, S, Hua, L, Liu, Y-H, Gao, L-C, Fu, J, Wan, D-Y, Dong, L-H, Song, H-F, Gao, X·2015·Gene Therapy
DOI 10.1038/gt.2015.2
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Abstract

The current therapies to treat hepatitis B virus (HBV) infection are limited. Recently, clustered regularly interspaced short palindromic repeat (CRISPR) systems, originally identified in bacteria and archaea, have been found to consist of an RNA-based adaptive immune system that degrades complimentary sequences of invading plasmids and viruses. Here, we studied the effects of the CRISPR/CRISPR-associated Cas9 system that was targeted to the surface antigen (HBsAg)-encoding region of HBV, both in a cell culture system and in vivo. The HBsAg levels in the media of the cells and in the sera of mice were analyzed by a quantitative enzyme-linked immunosorbent assay. The HBV DNA levels were assessed by quantitative PCR and HBsAg expression in mouse livers was assessed by an immunohistochemical assay. The amount of HBsAg secreted in the cell culture and mouse serum was reduced by CRISPR/Cas9 treatment. Immunohistochemistry analyses showed almost no HBsAg-positive cells in the liver tissue of CRISPR/Cas9-S1+X3-treated mice. The CRISPR/Cas9 system efficiently produced mutations in HBV DNA. Thus, CRISPR/Cas9 inhibits HBV replication and expression in vitro and in vivo and may constitute a new therapeutic strategy for HBV infection.

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  • PEI was used to deliver CRISPR plasmid DNA to inhibit HBV replication and gene expression in HBV-infected mice.

    “PEI was also used to deliver CRISPR plasmid DNA to inhibit HBV replication and gene expression in HBV-infected mice (Zhen et al., 2015).”

    From Delivering CRISPR: a review of the challenges and approaches (2018) · cites this paper as Zhen et al., 2015

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Metadata

Authors
Zhen, S., Hua, L., Liu, Y.-H., Gao, L.-C., Fu, J., Wan, D.-Y., Dong, L.-H., Song, H.-F., & Gao, X.
Venue
Gene Therapy
Publisher
Springer Science and Business Media LLC
Published
2015-02-05
Volume
22
Issue
5
Pages
404-412
ISSN
  • 0969-7128
  • 1476-5462
DOI
10.1038/gt.2015.2
Cited by
215
References
11
Language
en
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