新型修饰反义寡核苷酸对登革病毒的抑制作用
Inhibition of dengue virus by novel, modified antisense oligonucleotides.
作者信息
Raviprakash K, Liu K, Matteucci M, Wagner R, Riffenburgh R, Carl M
机构信息
Naval Medical Research Institute, Bethesda, Maryland 20889.
出版信息
J Virol. 1995 Jan;69(1):69-74. doi: 10.1128/JVI.69.1.69-74.1995.
Abstract
Five different target regions along the length of the dengue virus type 2 genome were compared for inhibition of the virus following intracellular injection of the cognate antisense oligonucleotides and their analogs. Unmodified phosphodiester oligonucleotides as well as the corresponding phosphorothioate oligonucleotides were ineffective in bringing about a significant inhibition of the virus. Novel modified phosphorothioate oligonucleotides in which the C-5 atoms of uridines and cytidines were replaced by propynyl groups caused a significant inhibition of the virus. Antisense oligonucleotide directed against the target region near the translation initiation site of dengue virus RNA was the most effective, followed by antisense oligonucleotide directed against a target in the 3' untranslated region of the virus RNA. It is suggested that the inhibitory effect of these novel modified oligonucleotides is due to their increased affinity for the target sequences and that they probably function via an RNase H cleavage of the oligonucleotide:RNA heteroduplex.
摘要
在向细胞内注射同源反义寡核苷酸及其类似物后，对登革病毒2型基因组全长的五个不同靶区域进行了病毒抑制比较。未修饰的磷酸二酯寡核苷酸以及相应的硫代磷酸寡核苷酸均无法对病毒产生显著抑制作用。尿苷和胞苷的C-5原子被丙炔基取代的新型修饰硫代磷酸寡核苷酸对病毒产生了显著抑制作用。针对登革病毒RNA翻译起始位点附近靶区域的反义寡核苷酸最为有效，其次是针对病毒RNA 3'非翻译区中一个靶标的反义寡核苷酸。提示这些新型修饰寡核苷酸的抑制作用归因于它们对靶序列亲和力的增加，并且它们可能通过核酸酶H切割寡核苷酸：RNA异源双链体发挥作用。
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