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Inhibition of hepatitis B virus (HBV) by LNA-mediated nuclear interference with HBV DNA transcription
Sun Zhen,Chen Hongyan #,Lu Daru *
School of Life Science,Fudan University
*Correspondence author
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Funding: This study was supported by grants from the State S&T Pro-jects of China （No.2008ZX10002-007) to Zhi Chen and by the Na-tional Natural Science Foundation of China）
Opened online: 9 January 2013
Accepted by: none
Citation: Sun Zhen,Chen Hongyan,Lu Daru.Inhibition of hepatitis B virus (HBV) by LNA-mediated nuclear interference with HBV DNA transcription[OL]. [ 9 January 2013] http://en.paper.edu.cn/en_releasepaper/content/4511934
 
 
Silencing target genes with small regulatory RNAs is widely used to investigate gene function and therapeutic drug development. Recently,triplex-based approaches have provided another attractive means to achieve targeted gene regulation and gene manipulation at the molecular and cellular levels. Nuclear entry of oligonucleotides and enhancement of their af?nity to the DNA targets are key points of such approaches. In this study, we developed lipid-based transport of a locked-nucleic-acid (LNA)-modi?ed oligonucleotide for hepatitis B virus (HBV) DNA interference in human hepatocytes expressing HBV genomic DNA. In these cells, the LNA-modi?ed oligonucleotides passed ef?ciently across the cell membrane, and lipid-coating facilitated translocation from the cytoplasm to the nucleus. The oligonucleotide specifically targeting HBV DNA clearly interfered with HBV DNA transcription as shown by a block in pregenomic RNA (pgRNA) production. The HBV DNA-targeted oligonucleotide suppressed HBV DNA replication and HBV protein production more ef?ciently than small interfering RNAs directed to the pgRNA. These results demonstrate that fusion with lipid can carry LNA-modi?ed oligonucleotides to the nucleus where they regulate gene expression. Interfering with HBV DNA transcription by LNA-mod-i?ed oligonucleotides has strong potential as a new strategy for HBV inhibition.
Keywords:RNA interference; Hepatocyte; Oligonucleotide; Lipofectamine; Triple-helix
 
 
 

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