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©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Aug 28, 2015; 21(32): 9554-9565
Published online Aug 28, 2015. doi: 10.3748/wjg.v21.i32.9554
Published online Aug 28, 2015. doi: 10.3748/wjg.v21.i32.9554
Dual gRNAs guided CRISPR/Cas9 system inhibits hepatitis B virus replication
Jie Wang, Rui-Yang Zhang, Shan-Long Ding, Lu Long, Xiang-Mei Chen, Hui Zhuang, Feng-Min Lu, State Key Laboratory of Natural and Biomimetic Drugs, Department of Microbiology and Infectious Disease Center, School of Basic Medicine, Peking University Health Science Center, Beijing 100191, China
Zhong-Wei Xu, Department of Gastroenterology, Pennsylvania Hospital, University of Pennsylvania, Philadelphia, PA 19104, United States
Shuang Liu, Beijing Artificial Liver Treatment and Training Center, Beijing Youan Hospital, Capital Medical University, Beijing 100069, China
Xiao-Meng Xie, Department of Epidemiology and Biostatistics, College of Public Health, Zhengzhou University, Zhengzhou 450001, Henan Province, China
Author contributions: Wang J, Xu ZW, Lu FM and Liu S designed the research; Wang J, Zhang RY, Ding SL, Long L and Xie XM performed the research; Wang J, Xu ZW, Lu FM, Liu S, Zhang RY and Xie XM analyzed the data; Wang J wrote the paper; Lu FM, Chen XM and Zhuang H revised the paper.
Supported by Natural Science Foundation of China, No. 81471938; the National S and T Major Project for Infectious Diseases, No. 2013ZX10002-002 and No. 2012ZX10002-005; and 111 Project, No. B07001.
Conflict-of-interest statement: The authors declare no conflicts of interest related to this manuscript.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Feng-Min Lu, MD, Professor, State Key Laboratory of Natural and Biomimetic Drugs, Department of Microbiology and Infectious Disease Center, School of Basic Medicine, Peking University Health Science Center, 38 Xueyuan Road, Beijing 100191, China. lu.fengmin@hsc.pku.edu.cn
Telephone: +86-10-82805136 Fax: +86-10-82805136
Received: February 13, 2015
Peer-review started: February 22, 2015
First decision: April 23, 2015
Revised: May 20, 2015
Accepted: July 8, 2015
Article in press: July 8, 2015
Published online: August 28, 2015
Peer-review started: February 22, 2015
First decision: April 23, 2015
Revised: May 20, 2015
Accepted: July 8, 2015
Article in press: July 8, 2015
Published online: August 28, 2015
Core Tip
Core tip: In this manuscript, 15 hepatitis B virus (HBV)-specific gRNAs were designed according to the HBV genome sequences of genotypes A-D. We confirmed that the CRISPR/Cas9 system with these HBV-specific gRNAs could efficiently suppress the replication of multiple HBV genotypes. Further, we demonstrated that dual gRNAs could guide the CRISPR/Cas9 system to efficiently destroy HBV cccDNA and reduce its level in HepAD38 cells. Since cccDNA, the template of HBV replication, accounts for the persistence of HBV infection, our data suggested that CRISPR/Cas9 technique may be a useful tool to eradicate HBV of multiple genotypes.