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    • 3. 发明申请
    • INFLUENZA POLYNUCLEOTIDES, EXPRESSION CONSTRUCTS, COMPOSITIONS, AND METHODS OF USE
    • 流感多核苷酸,表达结构,组成和使用方法
    • WO2008128176A1
    • 2008-10-23
    • PCT/US2008/060222
    • 2008-04-14
    • NUCLEONICS, INC.PACHUK, Catherine, J.MCCALLUS, Daniel, E.
    • PACHUK, Catherine, J.MCCALLUS, Daniel, E.
    • A01N43/04C07H21/02C07H21/04C12N5/00C12N5/02C12N15/00
    • C07K14/005A61K2039/53C12N2760/16122
    • The invention provides isolated RNA molecules containing a stretch of nucleotides from a conserved Influenza sequence, and provides complementary RNA molecules thereto. The RNA molecules of the invention are also substantially non-homologous to human sequences. The RNA molecules of the invention include double-stranded RNAs comprising a first region that is a conserved Influenza sequence, and a second region that is at least substantially complementary to the first region. Such double-stranded RNAs include single short hairpin RNAs (shRNAs) as well as multi-target hairpin RNAs containing a plurality, or several, stem-loop structures. The present invention further provides expression constructs that provide for expression of one, or a plurality, of RNA molecules of the invention. The RNA molecules, expression constructs, and compositions of the present invention find use in reducing levels of Influenza A RNA, in reducing Influenza A virus titer, and in treating or preventing Influenza virus infection. The invention is effective against at least human, swine and avian originating strains of Influenza A, and makes gene-silencing therapeutic strategies for combating Influenza A infection feasible.
    • 本发明提供了分离的RNA分子,其含有来自保守流感序列的一段核苷酸,并向其提供互补的RNA分子。 本发明的RNA分子也与人序列基本上不同源。 本发明的RNA分子包括双链RNA,其包含保守的流感序列的第一区域和至少基本上与第一区域互补的第二区域。 这样的双链RNA包括单短发夹RNA(shRNA)以及含有多个或几个茎环结构的多靶发夹RNA。 本发明还提供了表达本发明的一种或多种RNA分子的表达构建体。 本发明的RNA分子,表达构建体和组合物用于降低甲型流感病毒RNA水平,降低甲型流感病毒滴度,以及用于治疗或预防流感病毒感染。 本发明对至少人类,猪和禽流感A型流感病毒株有效,并且使抗甲型流感病毒的基因沉默治疗策略成为可能。