[Inhibitory effects of phosphorothioate antisense oligonucleotides on gene expression controlled by HCV 5'NCR in nude mice xenograft].
OBJECTIVE
To evaluate the activity in vivo of 3 phosphorothioate antisense oligonucleotides, HCV363, HCV279 and HCV349 using nude mice xenograft models based on the establishment of HCV 5' NCR transgenic cellular model (HepG2.9706).


METHODS
Female BALB/C nude mice, aged 4 to 6 weeks and weighing around 20g, were implanted s.c. with 100mul (106 cells) of the HepG2.9706 cells suspension in the lower-back region. In approximate 1 weeks, the animals were randomly grouped and intraperitoneally administrated the antisense drugs at 10 mg/kg body weight.


RESULTS
HCV363, HCV279 and HCV349 had obvious sequence-specific inhibitory effects on luciferase expression controlled by HCV 5' NCR in xenograft cells with the inhibitory rates of 80.4%, 78.6% and 47.9%, respectively. The effects of three different concentrations (5, 10, 20 mg/kg body weight) of HCV363 indicated that HCV363 increased the inhibitory activities on luciferase expression following the concentration raise and its inhibitory rate was up to 82.7%.


CONCLUSIONS
This study suggests that antisense oligonucleotides may provide a novel therapeutic approach to the treatment of HCV infection.
Wang
X
X
Institute of Radiation Medicine, Academy of Military Medical Sciences, Beijing 100850, China.
Wang
S
S
Guan
W
W
Mao
B
B
D000818:Animals; D005260:Female; D015967:Gene Expression Regulation, Viral / Q000187:drug effects*; D016174:Hepacivirus / Q000235:genetics*; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000235:genetics; D016376:Oligonucleotides, Antisense / Q000494:pharmacology*; D013873:Thionucleotides / Q000494:pharmacology*; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
D016376:Oligonucleotides, Antisense; D013873:Thionucleotides