CRISPR/Cas9 cleavage of viral DNA efficiently suppresses hepatitis B virus
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Zhang_CRISPR.pdf
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Author(s)
Shlomai, Amir
Michailidis, Eleftherios
Bhatta, Ankit
Rice, Charles M.
Ramanan, Vyas
Cox, David Benjamin Turitz
Scott, David Arthur
Zhang, Feng
Bhatia, Sangeeta N
Schwartz, Robert E.
Date Issued
June 2015
Journal
Scientific Reports
Publisher
Nature Publishing Group
Citation
Ramanan, Vyas; Shlomai, Amir; Cox, David B.T.; Schwartz, Robert E.; Michailidis, Eleftherios; Bhatta, Ankit et al. "CRISPR/Cas9 cleavage of viral DNA efficiently suppresses hepatitis B virus." Scientific Reports 5 (June 2015): 1083 © 2015 Macmillan Publishers Limited, part of Springer Nature
Version
Final published version
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.
MIT Department
Broad Institute of MIT and Harvard
Harvard University--MIT Division of Health Sciences and Technology
Massachusetts Institute of Technology. Department of Biology
Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences
McGovern Institute for Brain Research at MIT
Koch Institute for Integrative Cancer Research at MIT
Terms of Use
Creative Commons Attribution 4.0 International License
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DOI of Published Version
https://doi.org/10.1038/srep10833
