The effect of a series of antisense oligodeoxyribonucleotides [oligo(dN)] on the expression of the surface antigen (HBsAg) gene of human hepatitis B virus (HBV) was examined using hepatocellular carcinoma cells that contain integrated HBV genomes. Of a number of antisense oligo(dN)s tested, synthetic 15-mers directed at the cap site of mRNA and regions of the translational initiation site of the HBsAg gene were found to be highly effective and inhibited viral gene expression by as much as 96%. The inhibition was specific to the HBsAg gene and appeared to be at the level of translation. These results suggest a therapeutic potential for antisense oligo(dN) in the treatment of patients who are chronically infected with HBV.


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