Peyman A, Helsberg M, Kretzschmar G, Mag M, Grabley S, Uhlmann E
Hoechst AG, Frankfurt, Germany.
Biol Chem Hoppe Seyler. 1995 Mar;376(3):195-8. doi: 10.1515/bchm3.1995.376.3.195.
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.
在本研究中，我们阐明了确定针对特定靶点的活性序列是反义寡核苷酸疗法的主要障碍之一。针对单纯疱疹病毒1型（HSV-1）的不同靶基因以及这些基因内的不同位置，筛选了100种寡核苷酸以检测其抗病毒活性。为便于比较，所有寡核苷酸均采用相同的长度和相同的化学修饰：20聚体，在5'端和3'端均有两个硫代磷酸酯键。这种修饰未观察到序列非依赖性效应。令人惊讶的是，只有六种寡核苷酸显示出显著的抗病毒活性，其中活性最强的一种（#6）针对IE 110的翻译起始位点。
