[Inhibition of hepatitis B virus replication in vitro by phosphorothioate and tetradecyl phosphorothioate analogs of antisense oligonucleotide directed against precore and core regions].
In order to study the action of antisense oligonucleotide (ASON) against hepatitis B virus (HBV), the 2.2.15 cells were chosen as an in vitro cell culture assay system and phosphorothioate (PS) and tetradecyl PS analogs of a 16-mer ASON were synthesized against precore and core regions of HBV gene. ASONs could inhibit specifically 92%-95% of the HBsAg and 84%-87% of the HBeAg produced at a concentration of 10 mumol/L and depress the amount of HBV DNA in culture supernatant and cells. ASONs had no effect on cellular alpha-fetoprotein synthesis and no cytotoxicity. There was not any inhibitory effect on the expression of viral proteins with an unrelated oligonucleotide. At similar concentration, the tetradecyl PS ASON of the same length and sequence as PS ASON had a greater inhibitory effect and better permeation efficiency, so it seems to be a very promising drug to be developed.
Zhang
S
S
Affiliated Hospital of Luzhou Medical College, Sichuan.
Wang
S
S
Wang
Y
Y
D004279:DNA, Viral; D006514:Hepatitis B Surface Antigens / Q000096:biosynthesis; D006513:Hepatitis B e Antigens / Q000096:biosynthesis; D006515:Hepatitis B virus / Q000276:immunology / Q000502:physiology*; D016376:Oligonucleotides, Antisense / Q000494:pharmacology*; D014779:Virus Replication / Q000187:drug effects*
D004279:DNA, Viral; D006514:Hepatitis B Surface Antigens; D006513:Hepatitis B e Antigens; D016376:Oligonucleotides, Antisense