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

Vyas Ramanan, Amir Shlomai, David B.T. Cox, Robert E. Schwartz, Eleftherios Michailidis, Ankit Bhatta, David A. Scott, Feng Zhang, Charles M. Rice, Sangeeta N. Bhatia

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Article number10833
JournalScientific Reports
Volume5
DOIs
StatePublished - 2 Jun 2015

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