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.
Peyman
A
A
Hoechst AG, Frankfurt, Germany.
Helsberg
M
M
Kretzschmar
G
G
Mag
M
M
Grabley
S
S
Uhlmann
E
E
D001483:Base Sequence; D005814:Genes, Viral / Q000187:drug effects; D018259:Herpesvirus 1, Human / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D006801:Humans; D008969:Molecular Sequence Data; D016376:Oligonucleotides, Antisense / Q000494:pharmacology*; D012333:RNA, Messenger / Q000187:drug effects*; D012367:RNA, Viral / Q000187:drug effects*; D014779:Virus Replication / Q000187:drug effects*
D016376:Oligonucleotides, Antisense; D012333:RNA, Messenger; D012367:RNA, Viral