INHIBITION OF VIRAL GROWTH BY ANTISENSE OLIGONUCLEOTIDES DIRECTED AGAINST THE IE110 AND THE UL30 MESSENGER-RNA OF HERPES-SIMPLEX VIRUS TYPE-1

In the present work we elucidate that the identification of active seq uences for a given target is one of the principle hurdles of antisense oligonucleotide therapeutics. A number of 100 oligonucleotides direct ed against different target genes of HSV-1 and different locations wit hin those genes were screened for antiviral activity. To facilitate co mparison, the same length and the same chemical modification were used for all oligonucleotides: 20mers with two phosphorothioate linkages a t both the 5'- and the 3'-end. No sequence-independent effects were ob served with this type of modification. Surprisingly, only six oligonuc leotides did show significant antiviral activity, the most active one (# 6) being directed against the translation initiation site of IE 110 .