Seki M, Honda Y
Biosciences Laboratory, Mitsubishi Chemical Corporation, Yokohama.
J Biochem. 1995 Dec;118(6):1199-204. doi: 10.1093/oxfordjournals.jbchem.a125007.
Phosphorothioate antisense oligodeoxynucleotides (S-ODNs) designed to hybridize to the 5' region of the hepatitis C virus (HCV) genome were evaluated as to their ability to inhibit HCV gene expression, using an in vitro translation system. Three effective regions were found to interfere with the translation of HCV RNAs. These regions were region A [nucleotides (nt) 124 to 153], region B (nt 100 to 123), and region C (nt 324 to 360). Further detailed evaluation of S-ODNs within each region allowed us to propose some HCV-specific antiviral agent candidates. Two of them, SMS16 (nt 328 to 347) and SMS17 (nt 326 to 345), caused over 90% inhibition of HCV gene expression when present in a less than fourfold molar excess; this effect was sequence-specific and dose-dependent.
使用体外翻译系统，对设计用于与丙型肝炎病毒（HCV）基因组5'区域杂交的硫代磷酸反义寡脱氧核苷酸（S-ODN）抑制HCV基因表达的能力进行了评估。发现三个有效区域会干扰HCV RNA的翻译。这些区域是A区[核苷酸（nt）124至153]、B区（nt 100至123）和C区（nt 324至360）。对每个区域内的S-ODN进行进一步详细评估后，我们提出了一些HCV特异性抗病毒剂候选物。其中两种，SMS16（nt 328至347）和SMS17（nt 326至345），当以小于四倍摩尔过量存在时，可导致超过90%的HCV基因表达抑制；这种效应具有序列特异性且呈剂量依赖性。
