Zq. Yao et al., IN-VIVO INHIBITION OF HEPATITIS-B VIRAL GENE-EXPRESSION BY ANTISENSE PHOSPHOROTHIOATE OLIGODEOXYNUCLEOTIDES IN ATHYMIC NUDE-MICE, Journal of viral hepatitis, 3(1), 1996, pp. 19-22
Antisense oligodeoxynucleotides strategies have been used both to stud
y normal gene function and to block gene expression therapeutically. W
e have previously shown that a number of antisense oligonucleotides ag
ainst hepatitis B virus (HBV) mRNA are able to inhibit viral gene expr
ession in vitro, Here we report the establishment of an animal model p
roducing HBV markers in athymic nude mice and inhibition of HBV gene e
xpression and replication by antisense DNA in vivo. 2.2.15 cells (Hep-
G2 cell line transfected with HBV genomes) were injected subcutaneousl
y (s.c.) into athymic BALB/c nude mice at a total cell number of 0.5-1
x10(8) per mouse. Transplanted tumours developed about 2 weeks after i
noculation. Hepatitis B surface and e antigens (HBsAg and HBeAg), as w
ell as HBV DNA, could be detected in the circulation of tumour-bearing
mice, Hepatitis B surface antigen and hepatitis B core antigen (HBcAg
) were demonstrated in tumour cells, After 10 days of tumour growth, a
ntisense phosphorothioate oligonucleotide, complementary to the cap si
te of the SP II promoter of HBV mRNA, were injected by infiltration in
to or around the tumour as a daily dose of 20 mu g per gram body weigh
t. Treatment for a total of 10 days resulted in an effective inhibitio
n of viral replication and gene expression, These results suggest ther
apeutic potential for antisense oligomers in the treatment of patients
who are chronically infected with HBV.