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    Micro-RNA scaffolds and non-naturally occurring micro-RNAs
    1.
    发明授权
    Micro-RNA scaffolds and non-naturally occurring micro-RNAs 有权
    微RNA支架和非天然存在的微RNA

    公开(公告)号：US09353368B2

    公开(公告)日：2016-05-31

    申请号：US12601508

    申请日：2008-05-22

    申请人： Melissa Kelley ,  Amanda Birmingham ,  Jon Karpilow ,  Anastasia Khvorova ,  Kevin Sullivan

    发明人： Melissa Kelley ,  Amanda Birmingham ,  Jon Karpilow ,  Anastasia Khvorova ,  Kevin Sullivan

    IPC分类号： C12N15/11 ,  C07H21/04 ,  C12N15/113 ,  C12Q1/68

    CPC分类号： C12N15/113 ,  C12N15/111 ,  C12N2310/141 ,  C12N2310/531 ,  C12N2320/30 ,  C12N2330/30 ,  C12Q1/6869

    摘要： The present disclosure provides a non-naturally occurring miRNA having a stem-loop structure comprising a scaffold derived from a first endogenous miRNA (e.g., miR-196a-2 or miR-204), a mature strand derived from a second endogenous miRNA, and a star strand sequence that is at least partially complementary to the mature strand sequence. The present disclosure also provides a non-naturally occurring miRNA having a stem-loop structure comprising a scaffold derived from an endogenous miRNA (e.g., miR-196a-2 or miR-204), a mature strand designed t be at least partially complementary to a target RNA, and a star strand sequence that is at least partially complementary to the mature strand sequence. The methods and compositions of the disclosure may be used to mediate gene silencing via the RNAi pathway.

    摘要翻译： 本公开提供了非天然存在的具有茎环结构的miRNA，其包含源自第一内源miRNA（例如，miR-196a-2或miR-204）的支架，源自第二内源miRNA的成熟链，以及 与成熟链序列至少部分互补的星形链序列。 本公开还提供了非天然存在的miRNA，其具有包含源自内源miRNA（例如，miR-196a-2或miR-204）的支架的茎环结构，成熟链被设计为至少部分地与 靶RNA和与成熟链序列至少部分互补的星形链序列。 本公开的方法和组合物可用于通过RNAi途径介导基因沉默。

    MICRO-RNA SCAFFOLDS AND NON-NATURALLY OCCURRING MICRO-RNAS
    3.
    发明申请
    MICRO-RNA SCAFFOLDS AND NON-NATURALLY OCCURRING MICRO-RNAS 有权
    MICRO-RNA SCAFFOLDS和非天然产生的微RNA

    公开(公告)号：US20100292310A1

    公开(公告)日：2010-11-18

    申请号：US12601508

    申请日：2008-05-22

    申请人： Melissa Kelley ,  Amanda Birmingham ,  Jon Karpilow ,  Anastasia Khvorova ,  Kevin Sullivan

    发明人： Melissa Kelley ,  Amanda Birmingham ,  Jon Karpilow ,  Anastasia Khvorova ,  Kevin Sullivan

    IPC分类号： A61K31/7088 ,  C07H21/02 ,  C12N15/63 ,  C12N5/10

    CPC分类号： C12N15/113 ,  C12N15/111 ,  C12N2310/141 ,  C12N2310/531 ,  C12N2320/30 ,  C12N2330/30 ,  C12Q1/6869

    摘要： The present disclosure provides a non-naturally occurring miRNA having a stem-loop structure comprising a scaffold derived from a first endogenous miRNA (e.g., miR-196a-2 or miR-204), a mature strand derived from a second endogenous miRNA, and a star strand sequence that is at least partially complementary to the mature strand sequence. The present disclosure also provides a non-naturally occurring miRNA having a stem-loop structure comprising a scaffold derived from an endogenous miRNA (e.g., miR-196a-2 or miR-204), a mature strand designed t be at least partially complementary to a target RNA, and a star strand sequence that is at least partially complementary to the mature strand sequence. The methods and compositions of the disclosure may be used to mediate gene silencing via the RNAi pathway.

    摘要翻译： 本公开提供了非天然存在的具有茎环结构的miRNA，其包含源自第一内源miRNA（例如，miR-196a-2或miR-204）的支架，源自第二内源miRNA的成熟链，以及 与成熟链序列至少部分互补的星形链序列。 本公开还提供了非天然存在的miRNA，其具有包含源自内源miRNA（例如，miR-196a-2或miR-204）的支架的茎环结构，成熟链被设计为至少部分地与 靶RNA和与成熟链序列至少部分互补的星形链序列。 本公开的方法和组合物可用于通过RNAi途径介导基因沉默。

    COMPOSITIONS AND METHODS FOR INHIBITING GENE SILENCING BY RNA INTERFERENCE
    8.
    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。