CRISPR/Cas9 cleavage of viral DNA efficiently suppresses hepatitis B virus
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.; ... Show more Show less
MetadataShow full item record
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.
DepartmentBroad 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
Nature Publishing Group
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
Final published version