MODIFIED OLIGORIBONUCLEOTIDE ANALOGS WITH ENHANCED IMMUNOSTIMULATORY ACTIVITY
    22.
    发明申请
    MODIFIED OLIGORIBONUCLEOTIDE ANALOGS WITH ENHANCED IMMUNOSTIMULATORY ACTIVITY 审中-公开
    改良的寡核苷酸类似物与增强的免疫活性

    公开(公告)号:US20110244025A1

    公开(公告)日:2011-10-06

    申请号:US12946379

    申请日:2010-11-15

    摘要: The invention provides immunostimulatory compositions and methods for their use. In particular, the immunostimulatory compositions of the invention include RNA-like polymers that incorporate an immunostimulatory sequence motif and at least one chemical modification to confer improved stability against nuclease degradation and improved activity. Specific modifications involving phosphate linkages, nucleotide analogs, and combinations thereof are provided. Compositions of the invention optionally include an antigen and can be used to stimulate an immune response. Also provided are compositions and methods useful for treating a subject having an infection, a cancer, an to allergic condition, or asthma. Modified oligoribonucleotide analogs of the invention are believed to stimulate Toll-like receptors TLR7 and TLR8.

    摘要翻译: 本发明提供免疫刺激组合物及其使用方法。 特别地,本发明的免疫刺激组合物包括纳入免疫刺激序列基序的RNA样聚合物和至少一种化学修饰,以提供改善的对核酸酶降解的稳定性和改善的活性。 提供了涉及磷酸键,核苷酸类似物及其组合的具体修饰。 本发明的组合物任选地包括抗原并且可以用于刺激免疫应答。 还提供了可用于治疗感染,癌症,过敏性疾病或哮喘的受试者的组合物和方法。 据信本发明的修饰的寡核糖核苷酸类似物刺激Toll样受体TLR7和TLR8。

    High efficacy antisense RIαPKA poly-DNP oligoribonucleotides
    23.
    发明授权
    High efficacy antisense RIαPKA poly-DNP oligoribonucleotides 失效
    高效反义RIalphaPKA多聚DNP寡核糖核苷酸

    公开(公告)号:US07528117B2

    公开(公告)日:2009-05-05

    申请号:US10728491

    申请日:2003-12-05

    摘要: The present invention discloses antisense poly-2′-O-(2,4-dinitrophenyl) oligoribonucleotides which are capable of down regulating the expression of the RIα subunit of protein kinase A. An example is 5′-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 RIα/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。

    In Vitro and in vivo silencing of human c-myc oncogene expression by poly-DNP-RNA
    24.
    发明申请
    In Vitro and in vivo silencing of human c-myc oncogene expression by poly-DNP-RNA 审中-公开
    体外和体内沉默人类c-myc癌基因表达多聚DNP-RNA

    公开(公告)号:US20060122140A1

    公开(公告)日:2006-06-08

    申请号:US11284693

    申请日:2005-11-22

    IPC分类号: A61K48/00

    摘要: The present invention provides antisense oligoribonucleotides with sequences that recognize and bind to the c-myc gene or c-myc mRNA, where one or more sugar residues of the oligoribonucleotides are modified by the substitution of DNP at the 2′-O position. The antisense oligoribonucleotides can be used for inhibiting the growth of cells in which the c-myc gene is overexpressed by down-regulation of transcription of c-myc RNA or translation of the c-myc protein. The antisense oligoribonucleotides can also be used for diagnostic purposes to identify the overexpression of the c-myc gene. The nucleotide sequence of the DNP-oligoribonucleotides is complementary to the sequence 578 to 598 in c-myc mRNA and does not contain a G-quartet motif. This DNP-RNA can silence c-myc gene expression both in vitro and in vivo with high efficacy and sequence specificity.

    摘要翻译: 本发明提供了具有识别和结合c-myc基因或c-myc mRNA的序列的反义寡核苷酸,其中寡核糖核苷酸的一个或多个糖残基通过在2'-O位置处的DNP的取代被修饰。 反义寡核糖核苷酸可用于抑制c-myc基因通过下调c-myc RNA的转录或c-myc蛋白的翻译而过表达的细胞的生长。 反义寡核糖核酸也可用于诊断目的,以鉴定c-myc基因的过表达。 DNP-寡核糖核苷酸的核苷酸序列与c-myc mRNA中的序列578至598互补,并且不含G-四重基序列。 该DNP-RNA可以在体外和体内沉默c-myc基因表达,具有高效和序列特异性。