CRISPR/Cas9 cleavage of viral DNA efficiently suppresses hepatitis B virus.

Sci Rep
Authors
Keywords
Abstract

Chronic hepatitis B virus (HBV) infection is prevalent, deadly, and seldom cured due to the persistence of viral episomal DNA (cccDNA) in infected cells. Newly developed genome engineering tools may offer the ability to directly cleave viral DNA, thereby promoting viral clearance. Here, we show that the CRISPR/Cas9 system can specifically target and cleave conserved regions in the HBV genome, resulting in robust suppression of viral gene expression and replication. Upon sustained expression of Cas9 and appropriately chosen guide RNAs, we demonstrate cleavage of cccDNA by Cas9 and a dramatic reduction in both cccDNA and other parameters of viral gene expression and replication. Thus, we show that directly targeting viral episomal DNA is a novel therapeutic approach to control the virus and possibly cure patients.

Year of Publication
2015
Journal
Sci Rep
Volume
5
Pages
10833
Date Published
2015 Jun 02
ISSN
2045-2322
URL
DOI
10.1038/srep10833
PubMed ID
26035283
PubMed Central ID
PMC4649911
Links
Grant list
UL1 TR000043 / TR / NCATS NIH HHS / United States
R01 MH110049 / MH / NIMH NIH HHS / United States
1K08DK101754 / DK / NIDDK NIH HHS / United States
5DP1-MH100706 / DP / NCCDPHP CDC HHS / United States
P30 CA014051 / CA / NCI NIH HHS / United States
R01 DK085713 / DK / NIDDK NIH HHS / United States
T32 GM007753 / GM / NIGMS NIH HHS / United States
P30-CA14051 / CA / NCI NIH HHS / United States
P30 ES002109 / ES / NIEHS NIH HHS / United States
8 UL1 TR000043 / TR / NCATS NIH HHS / United States
DP1 MH100706 / MH / NIMH NIH HHS / United States
R01 NS073124 / NS / NINDS NIH HHS / United States
Howard Hughes Medical Institute / United States
5R01-NS073124 / NS / NINDS NIH HHS / United States
DK085713 / DK / NIDDK NIH HHS / United States
T32GM007753 / GM / NIGMS NIH HHS / United States
K08 DK101754 / DK / NIDDK NIH HHS / United States
P30-ES002109 / ES / NIEHS NIH HHS / United States