Phosphorothioate antisense oligodeoxynucleotides capable of inhibiting hepatitis C virus gene expression: in vitro translation assay.

Phosphorothioate antisense oligodeoxynucleotides (S-ODNs) designed to hybridize to the 5' region of the hepatitis C virus (HCV) genome were evaluated as to their ability to inhibit HCV gene expression, using an in vitro translation system. Three effective regions were found to interfere with the translation of HCV RNAs. These regions were region A [nucleotides (nt) 124 to 153], region B (nt 100 to 123), and region C (nt 324 to 360). Further detailed evaluation of S-ODNs within each region allowed us to propose some HCV-specific antiviral agent candidates. Two of them, SMS16 (nt 328 to 347) and SMS17 (nt 326 to 345), caused over 90% inhibition of HCV gene expression when present in a less than fourfold molar excess; this effect was sequence-specific and dose-dependent.