Inhibition of viral growth by antisense oligonucleotides directed against the IE110 and the UL30 mRNA of herpes simplex virus type-1.

In the present work we elucidate that the identification of active sequences for a given target is one of the principle hurdles of antisense oligonucleotide therapeutics. A number of 100 oligonucleotides directed against different target genes of HSV-1 and different locations within those genes were screened for antiviral activity. To facilitate comparison, the same length and the same chemical modification were used for all oligonucleotides: 20mers with two phosphorothioate linkages at both the 5'- and the 3'-end. No sequence-independent effects were observed with this type of modification. Surprisingly, only six oligonucleotides did show significant antiviral activity, the most active one (#6) being directed against the translation initiation site of IE 110.