Long-term inhibition of hepatitis B virus in transgenic mice by double-stranded adeno-associated virus 8-delivered short hairpin RNA

C. C. Chen, Tai-Ming Ko, H. I. Ma, H. L. Wu, X. Xiao, J. Li, C. M. Chang, P. Y. Wu, C. H. Chen, J. M. Han, C. P. Yu, K. S. Jeng, C. P. Hu, M. H. Tao*

*此作品的通信作者

研究成果: Article同行評審

69 引文 斯高帕斯(Scopus)

摘要

RNA interference (RNAi) was reported to block hepatitis B virus (HBV) gene expression and replication in vitro and in vivo. However, it remains a technical challenge for RNAi-based therapy to achieve long-term and complete inhibition effects in chronic HBV infection, which presumably requires more extensive and uniform transduction of the whole infected hepatocytes. To increase the in vivo transfection efficiency in liver, we used a double-stranded adeno-associated virus 8-pseudotyped vector (dsAAV2/8) to deliver shRNA. HBV transgenic mice were used as an animal model to evaluate the inhibition effects of the RNAi-based gene therapy. A single administration of dsAAV2/8 vector, carrying HBV-specific shRNA, effectively suppressed the steady level of HBV protein, mRNA and replicative DNA in liver of HBV transgenic mice, leading to up to 2-3 log10 decrease in HBV load in the circulation. Significant HBV suppression sustained for at least 120 days after vector administration. The therapeutic effect of shRNA was target sequence dependent and did not involve activation of interferon. These results underscore the potential for developing RNAi-based therapy by dsAAV2/8 vector to treat HBV chronic infection, and possibly other persistent liver infections as well.

原文English
頁(從 - 到)11-19
頁數9
期刊Gene Therapy
14
發行號1
DOIs
出版狀態Published - 1月 2007

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