IN-VIVO INHIBITION OF HEPATITIS-B VIRUS GENE-EXPRESSION BY ANTISENSE PHOSPHOROTHIOATE OLIGONUCLEOTIDES

While an important goal of treatment for hepatitis B is to prevent the development of hepatocellular carcinoma, there has been no effective therapy for it. Antisense oligodeoxynucleotide treatment could in prin ciple inhibit hepatitis B virus gene expression and suppress tumor dev elopment. We used a mouse model for hepatocellular carcinoma, which is transgenic for the hepatitis B virus HBx gene, to study antisense pho sphorothioate oligodeoxynucleotides. Among 2 series of sense and antis ense oligodeoxynucleotides, only antisense sequences covering the init iation codon of the HBx gene effectively inhibited the expression of t he HBx gene in the liver. Intraperitoneal injection of this antisense oligodeoxynucleotide thrice a week for 8 weeks resulted in the prevent ion of preneoplastic lesion development in the liver without inflammat ion in the liver or developmental disturbance of the mice. Antisense p hosphorothioate oligodeoxynucleotides can inhibit the expression of a hepatitis B virus gene and may be a promising method for the preventio n of hepatocellular carcinoma in hepatitis B virus infection. (C) 1996 Academic Press