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    Poly-DNP-siRNA
    3.
    发明申请
    Poly-DNP-siRNA 审中-公开

    公开(公告)号：US20040248841A1

    公开(公告)日：2004-12-09

    申请号：US10801118

    申请日：2004-03-15

    发明人： Jui H. Wang ,  Hongtao Liao ,  Long Shen ,  Xiaolan Chen

    IPC分类号： A61K048/00 ,  C07H021/02

    CPC分类号： C12N15/1135 ,  C07H21/02 ,  C12N15/111 ,  C12N15/1137 ,  C12N15/1138 ,  C12N2310/14 ,  C12N2310/321 ,  C12N2320/51 ,  C12N2310/3529

    摘要： Embodiments of the present invention provide methods and for improving the stability or efficacy of the double stranded siRNAs by replacing either one or both of its native RNA strands with homologous RNase-resistant poly-DNP-RNA to form poly-DNP-siRNA, where DNP denotes a 2null-O-(2,4-dinitrophenyl) represented by the structure: 1 wherein R2, R4, and R5 are independently H, halide, linear or branched alkyl, linear or branched acyl, linear or branched alkylene, linear or branched O-alkyl, linear or branched amido, linear or branched S-alkyl, mono or disubstituted amine, linear or branched thioamido, phosphothionate, or phosphothioate. Additional embodiments include DNP-derivatized siRNAs with improved stability or efficacy compared to non-DNP-derivatized siRNAs.

    摘要翻译： 本发明的实施方案提供了通过用同源的RNA酶抗性多聚DNP-RNA替换其天然RNA链中的一个或两个来形成多聚DNP-siRNA来提供双链siRNAs的稳定性或功效的方法和用于改善双链siRNA的稳定性或功效，其中DNP 表示由以下结构表示的2'-O-（2,4-二硝基苯基）：其中R 2，R 4和R 5独立地为H，卤素，直链或支链烷基，直链或支链酰基 直链或支链的亚烷基，直链或支链的O-烷基，直链或支链的酰胺基，直链或支链的S-烷基，单或二取代的胺，直链或支链的硫代酰氨基，磷酸酯或磷酸硫酸酯。 另外的实施方案包括与非DNP衍生的siRNA相比具有改进的稳定性或功效的DNP衍生的siRNA。

    High efficacy antisense RIalpha PKA poly-DNP oligoribonucleotides
    10.
    发明申请
    High efficacy antisense RIalpha PKA poly-DNP oligoribonucleotides 失效
    高效反义RIalpha PKA多聚DNP寡核糖核苷酸

    公开(公告)号：US20040142896A1

    公开(公告)日：2004-07-22

    申请号：US10728491

    申请日：2003-12-05

    发明人： Jui H. Wang ,  Long Shen ,  Xiaolan Chen

    IPC分类号： A61K048/00 ,  C07H021/04

    CPC分类号： C12N15/113 ,  A61K38/00 ,  C12N15/1137 ,  C12N2310/321 ,  C12N2310/3529

    摘要： The present invention discloses antisense poly-2null-O-(2,4-dinitrophenyl) oligoribonucleotides which are capable of down regulating the expression of the RInull subunit of protein kinase A. An example is 5null-GGCUGCGUGCCUCCUCACUGG (named antisense poly-DNP RNA-21) or a sequence which has a one-base mismatch therewith. The antisense oligoribonucleotide can be synthesized by in vitro transcription followed by chemical derivatization. The base sequence of the oligoribonucleotides is complementary to that of nt 110 to 130 in RInull/PKA mRNA. The antisense poly-DNP RNA-21 was found to inhibit cell growth with IC50 values in the nanomolar range. These oligonucleotides can be used as effective anti-cancer agents.

    摘要翻译： 本发明公开了能够下调蛋白激酶A的RIalpha亚基表达的反式多聚-2'-O-（2,4-二硝基苯基）寡核糖核苷酸。一个实例是5'-GGCUGCGUGCCUCCUCACUGG（命名为反义多聚DNP RNA-21）或与其单碱基错配的序列。 反义寡核苷酸可以通过体外转录，然后进行化学衍生化合成。 寡核糖核苷酸的碱基序列与RIalpha / PKA mRNA中的nt 110至130的碱基序列互补。 发现反义多聚DNP RNA-21抑制细胞生长，其IC50值在纳摩尔范围内。 这些寡核苷酸可以用作有效的抗癌剂。