INHIBITION OF HERPES-SIMPLEX VIRUS-1 REPRODUCTION WITH HYDROPHOBIZED ANTISENSE OLIGONUCLEOTIDES

Antisense oligonucleotides were modified by their ends with hydrophobi c substituents which permitted enhancing their activity. The effect of hydrophobized oligonucleotides on reproduction of Herpes Simplex Viru s type 1 in Vero cells was studied. Two types of oligonucleotides were used: a 12-mer complementary to the splicing site 983-994 of early mR NA-5 of the virus and 19-mer complementary to the site of mRNA that en codes the virus DNA-polymerase. These oligonucleotides were modified b y 5'-ends with n-undecyl or cholesteryl moieties and by 3'-ends with a cridine or 1,7-heptanediol. In comparison with the unnmodified oligonu cleotides the hydrophobized ones were significantly more active and in hibited HSV-1 infection at micromolar concentrations. (C) 1994 Academi c Press, Inc.