Mixed-backbone oligonucleotides as second generation antisense oligonucleotides: In vitro and in vivo studies
Mixed-backbone oligonucleotides as second generation antisense oligonucleotides: In vitro and in vivo studies
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DOI：
10.1073/pnas.94.6.2620
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发表时间：
1997-03-18
影响因子：
11.1
通讯作者：
Zhang, RW
中科院分区：
文献类型：
--
作者：
Agrawal, S;Jiang, ZW;Zhang, RW
反义寡核苷酸作为新型治疗药物正在临床试验中得到评价。为了进一步改善反义寡核苷酸的性质，我们设计了混合骨架寡核苷酸（MBOs），它在3‘和5’端含有磷酸化片段，并在寡核苷酸的中心部分含有修饰的寡脱氧核苷酸或寡核糖核苷酸片段。与硫代寡脱氧核苷酸相比，其中一些mbo在对RNA的亲和力、RNase H活化和抗hiv活性方面表现出更好的特性。此外，这些mbo获得了更可接受的药理学、体内降解和药代动力学特征。
Antisense oligonucleotides are being evaluated in clinical trials as novel therapeutic agents. To further improve the properties of antisense oligonucleotides, we have designed mixed-backbone oligonucleotides (MBOs) Bat contain phosphorothioate segments at the 3' and 5' ends and have a modified oligodeoxynucleotide or oligoribonucleotide segment located in the central portion of the oligonucleotide. Some of these MBOs indicate improved properties compared with phosphorothioate oligodeoxynucleotides with respect to affinity to RNA, RNase H activation, and anti-HIV activity. In addition, more acceptable pharmacological, in vivo degradation and pharmacokinetic profiles were obtained with these MBOs.