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    COMPOSITIONS AND METHODS FOR INHIBITING GENE SILENCING BY RNA INTERFERENCE
    5.
    发明申请
    COMPOSITIONS AND METHODS FOR INHIBITING GENE SILENCING BY RNA INTERFERENCE 审中-公开
    通过RNA干扰抑制基因沉默的组合物和方法

    公开(公告)号：US20100184209A1

    公开(公告)日：2010-07-22

    申请号：US12279594

    申请日：2007-02-16

    申请人： Annaleen Vermeulen ,  Barbara Robertson ,  Scott Baskerville ,  Christina Yamada ,  Devin Leake ,  Yuriy Fedorov ,  Jon Karpilow ,  Anastasia Khvorova

    发明人： Annaleen Vermeulen ,  Barbara Robertson ,  Scott Baskerville ,  Christina Yamada ,  Devin Leake ,  Yuriy Fedorov ,  Jon Karpilow ,  Anastasia Khvorova

    IPC分类号： C12N5/071 ,  C07H21/02

    CPC分类号： C12N15/111 ,  C12N15/113 ,  C12N2310/11 ,  C12N2310/321 ,  C12N2310/3515 ,  C12N2310/53 ,  C12N2320/50 ,  C12N2310/3521

    摘要： The present invention provides compositions and methods for inhibiting gene silencing by the RNAi pathway. The RNAi inhibitors of the invention have a reverse complement (RC) region to the target molecule of interest (e.g., miRNA) in association with at least one flanking region coupled to either at the 3′ or 5′ end of the RC region. The flanking regions can be single-stranded or can have one or more regions of double stranded nucleic acid with or without a hairpin loop. The RNAi inhibitors described herein can inhibit endogenous targets, including but not limited to microRNAs, or piRNAs, or can be used to inhibit the effects of exogenously introduced molecules, such as synthetic siRNAs, siRNAs expressed from vector constructs (e.g., viral expression systems), or siRNAs generated by enzymatic methods. Inhibition is specific, potent, prolonged, and can be performed on a single target or multiple targets simultaneously.

    摘要翻译： 本发明提供了通过RNAi途径抑制基因沉默的组合物和方法。 本发明的RNAi抑制剂与至少一个与RC区的3'或5'末端连接的侧翼区域具有与目的靶分子（例如miRNA）的反向互补序列（RC）区域。 侧翼区域可以是单链的或可以具有一个或多个具有或不具有发夹环的双链核酸区域。 本文所述的RNAi抑制剂可抑制内源性靶标，包括但不限于微小RNA或piRNA，或可用于抑制外源引入分子如合成siRNAs，由载体构建体（例如病毒表达系统）表达的siRNA的作用， ，或通过酶法产生的siRNA。 抑制是具体的，有效的，延长的，并且可以同时在单个靶或多个靶上进行。

    Highly functional short hairpin RNA
    6.
    发明申请
    Highly functional short hairpin RNA 审中-公开
    高度功能的短发夹RNA

    公开(公告)号：US20060223777A1

    公开(公告)日：2006-10-05

    申请号：US11390829

    申请日：2006-03-28

    申请人： Annaleen Vermeulen ,  Angela Reynolds ,  Jon Karpilow ,  Devin Leake ,  Xiaoqin Cheng ,  Stephanie Hartsel ,  Anastasia Khvorova

    发明人： Annaleen Vermeulen ,  Angela Reynolds ,  Jon Karpilow ,  Devin Leake ,  Xiaoqin Cheng ,  Stephanie Hartsel ,  Anastasia Khvorova

    IPC分类号： A61K48/00 ,  C07F9/6512 ,  C07H21/02 ,  C12N15/00

    CPC分类号： C12N15/111 ,  C12N2310/14 ,  C12N2310/321 ,  C12N2310/53 ,  C12N2330/30 ,  C12N2310/3521

    摘要： The present invention provides improved hairpin and fractured hairpin constructs for use in gene silencing through the RNA interference pathway. An exemplary short hairpin polynucleotide for use in gene silencing can include a polynucleotide having from about 42 nucleotides to about 106 nucleotides configured for being processed by Dicer. The polynucleotide can include a first region having from about 19 to about 35 nucleotides, a loop region coupled to the first region, the loop region having from about 4 to about 30 nucleotides, and a second region having from about 19 to about 35 nucleotides and having at least about 80% complementarity to the first region. Optionally, one of the first region or second region can have an overhang having less than about 6 nucleotides. Also, the short hairpin can be formed of a plurality of polynucleotides that cooperate to form a hairpin structure.

    摘要翻译： 本发明提供用于通过RNA干扰途径进行基因沉默的改良的发夹和断裂发夹构建体。 用于基因沉默的示例性短发夹多核苷酸可以包括具有约42个核苷酸至约106个核苷酸的多核苷酸，其被配置为由Dicer加工。 多核苷酸可以包括具有约19至约35个核苷酸的第一区域，耦合到第一区域的环区域，具有约4至约30个核苷酸的环区域和具有约19至约35个核苷酸的第二区域和具有约19至约35个核苷酸的第二区域， 与第一个区域具有至少约80％的互补性。 任选地，第一区域或第二区域之一可以具有小于约6个核苷酸的突出端。 此外，短发夹可以由多个多核苷酸形成，其协作形成发夹结构。

    SCREENING OF MICRO-RNA CLUSTER INHIBITOR POOLS
    7.
    发明申请
    SCREENING OF MICRO-RNA CLUSTER INHIBITOR POOLS 有权
    微RNA聚集体抑制剂池的筛选

    公开(公告)号：US20100273856A1

    公开(公告)日：2010-10-28

    申请号：US12670363

    申请日：2008-07-21

    申请人： Anja Smith ,  Scott Baskerville ,  Devin Leake ,  Annaleen Vermeulen ,  Barbara Robertson ,  Anastasia Khvorova

    发明人： Anja Smith ,  Scott Baskerville ,  Devin Leake ,  Annaleen Vermeulen ,  Barbara Robertson ,  Anastasia Khvorova

    IPC分类号： A61K31/7105 ,  C12Q1/68 ,  C12N5/09 ,  A61P35/00

    CPC分类号： C12N15/111 ,  C12N2310/113 ,  C12N2310/141 ,  C12N2320/12 ,  C12N2330/10 ,  C12Q1/6886 ,  C12Q2600/178

    摘要： The disclosure provides methods for inhibiting the activity of a miRNA cluster in a cell, and also for screening a cell for a phenotype(s) of interest resulting from inhibition of a miRNA cluster. The methods use a cluster pool which comprises at least one miRNA inhibitor specific for each miRNA in the miRNA cluster. MiRNA inhibitors are described that induce apoptosis in breast cancer cells and hence are useful in the treatment of breast cancer. The disclosure also provides pharmaceutical compositions which are useful for the treatment of breast cancer; methods for inducing the nuclear translocation of NF-κB in a breast cancer cell; methods for inducing the nuclear translocation of c-Jun in a breast cancer cell; method for inhibiting the nuclear translocation of NF-κB in a breast cancer cell; and methods for providing prognostic medical information relating to breast cancer progression.

    摘要翻译： 本公开提供了抑制细胞中miRNA簇的活性的方法，以及用于筛选由miRNA群抑制引起的表型的细胞。 该方法使用聚类池，其包含至少一种对miRNA簇中的每个miRNA特异的miRNA抑制剂。 描述了诱导乳腺癌细胞凋亡的MiRNA抑制剂，因此可用于治疗乳腺癌。 本公开还提供了可用于治疗乳腺癌的药物组合物; 在乳腺癌细胞中诱导NF-κB的核易位的方法; 在乳腺癌细胞中诱导c-Jun的核易位的方法; 抑制乳腺癌细胞中NF-κB的核易位的方法; 以及用于提供与乳腺癌进展相关的预后医学信息的方法。

    Screening of micro-RNA cluster inhibitor pools
    9.
    发明授权
    Screening of micro-RNA cluster inhibitor pools 有权
    筛选微RNA聚类抑制剂池

    公开(公告)号：US08367318B2

    公开(公告)日：2013-02-05

    申请号：US12670363

    申请日：2008-07-21

    申请人： Anja Smith ,  Scott Baskerville ,  Devin Leake ,  Annaleen Vermeulen ,  Barbara Robertson ,  Anastasia Khvorova

    发明人： Anja Smith ,  Scott Baskerville ,  Devin Leake ,  Annaleen Vermeulen ,  Barbara Robertson ,  Anastasia Khvorova

    IPC分类号： C12Q1/68

    CPC分类号： C12N15/111 ,  C12N2310/113 ,  C12N2310/141 ,  C12N2320/12 ,  C12N2330/10 ,  C12Q1/6886 ,  C12Q2600/178

    摘要： The disclosure provides methods for inhibiting the activity of a miRNA cluster in a cell, and also for screening a cell for a phenotype(s) of interest resulting from inhibition of a miRNA cluster. The methods use a cluster pool which comprises at least one miRNA inhibitor specific for each miRNA in the miRNA cluster. MiRNA inhibitors are described that induce apoptosis in breast cancer cells and hence are useful in the treatment of breast cancer. The disclosure also provides pharmaceutical compositions which are useful for the treatment of breast cancer; methods for inducing the nuclear translocation of NF-κB in a breast cancer cell; methods for inducing the nuclear translocation of c-Jun in a breast cancer cell; method for inhibiting the nuclear translocation of NF-κB in a breast cancer cell; and methods for providing prognostic medical information relating to breast cancer progression.

    摘要翻译： 本公开提供了抑制细胞中miRNA簇的活性的方法，以及用于筛选由miRNA群抑制引起的表型的细胞。 该方法使用聚类池，其包含至少一种对miRNA簇中的每个miRNA特异的miRNA抑制剂。 描述了诱导乳腺癌细胞凋亡的MiRNA抑制剂，因此可用于治疗乳腺癌。 本公开还提供了可用于治疗乳腺癌的药物组合物; 在乳腺癌细胞中诱导NF-κB的核易位的方法; 在乳腺癌细胞中诱导c-Jun的核易位的方法; 抑制乳腺癌细胞中NF-κB的核易位的方法; 以及用于提供与乳腺癌进展相关的预后医学信息的方法。