Chinese Science Bulletin ISSN:1001-6538 2004 Vol.49 No.14 1470-1475
RNA interference-mediated inhibition of Hepatitis B Virus replication
TANG Ni1, ZHANG Bingqiang1, YAN Ge1, PU Dan1, GAO Xiaolin1,
Tong-Chuan He2 & HUANG Ailong1
1. The Institute for Viral Hepatitis, Chongqing University of Medical Sciences, Chongqing 400010, China;
2. Molecular Oncology Laboratory, The University of Chicago Medical Center, Chicago, IL 60637, USA
Correspondence should be addressed to Huang Ailong (e-mail: [email protected])
Abstract Persistent and recurrent infection of hepatitis B virus (HBV) represents one of the most common and severe viral infections of humans, and has caused a formidable health problem in the affected countries. Currently used antiviral drugs have a very limited success on controlling HBV replication and infection. RNA interference (RNAi), a process by which double-stranded RNA (dsRNA) directs sequence-specific degradation of target mRNA in mammalian and plant cells, has recently been used to knockdown gene expression in various species. In this study, we sought to determine whether RNAi-mediated silencing of HBV viral gene expression could lead to the effective inhibition of HBV replication. We first developed RNAi vectors that expressed small interfering RNA (siRNA) and targeted the HBV core or surface gene sequence. Our results demonstrated that these specific siRNAs efficiently reduced the levels of corresponding viral RNAs and proteins, and thus suppressed viral replication. Treatment with siRNA gave the greatest reduction in the levels of HBsAg (92%) and in HBeAg (85%) respectively in the cultured cell medium. Our findings further demonstrated that the RNAi-mediated antiviral effect was sequence-specific and dose-dependent. Therefore, our findings strongly suggest that RNAi-mediated silencing of HBV viral genes could effectively inhibit the replication of HBV, hence RNAi-based strategy should be further explored as a more efficacious antiviral therapy of HBV infection.
Keywords: antiviral therapy, Hepatitis B virus, RNA interference, viral replication, gene therapy.
DOI: 10.1360/04wc0096
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发表于 2004-10-29 02:23
