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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。

    Identification of toxic nucleotide sequences
    5.
    发明申请
    Identification of toxic nucleotide sequences 审中-公开
    鉴定毒性核苷酸序列

    公开(公告)号：US20050203043A1

    公开(公告)日：2005-09-15

    申请号：US11040553

    申请日：2005-01-21

    申请人： Yuriy Fedorov ,  Jon Karpilow ,  Anastasia Khvorova

    发明人： Yuriy Fedorov ,  Jon Karpilow ,  Anastasia Khvorova

    IPC分类号： C07H21/02 ,  C07H21/04 ,  C12N15/11 ,  C12Q1/68 ,  G01N33/48 ,  G01N33/50 ,  G06F19/00

    CPC分类号： C12Q1/6883 ,  C12N15/111 ,  C12N2310/14 ,  C12N2310/53 ,  C12N2320/10 ,  C12Q2600/142

    摘要： Toxic nucleic acid sequences and methods for identifying, using, and screening libraries for them, including in silico screening, are provided. Compositions of the invention comprise unimolecular and double stranded polynucleotides comprising at least one toxicity region. Toxic sequences of the invention include A/G UUU A/G/U, G/C AAA G/C, and/or GCCA, NUUU, wherein N is any nucleotide, or complements thereof. The invention also provides a method of inducing a toxic response in a cell, comprising introducing into the cell a unimolecular or double stranded polynucleotide comprising at least one toxicity region comprising a sequence selected from the group consisting of A/G UUU A/G/U, G/C AAA G/C, GAAT, and GCCA, NUUU, wherein N is any nucleotide, or a complement of any of the foregoing, wherein said unimolecular or double stranded polynucleotide is at least 5 base pairs long and is comprises a sense and antisense region that are at least substantially complementary.

    摘要翻译： 提供了有毒的核酸序列和用于识别，使用和筛选其文库的方法，包括计算机筛选。 本发明的组合物包含包含至少一个毒性区域的单分子和双链多核苷酸。 本发明的毒性序列包括A / G UUU A / G / U，G / C AAA G / C和/或GCCA，NUUU，其中N是任何核苷酸或其互补序列。 本发明还提供了在细胞中诱导毒性反应的方法，包括向细胞中引入单分子或双链多核苷酸，所述单分子或双链多核苷酸包含至少一个毒性区，其包含选自A / G UUU A / G / U ，G / C AAA G / C，GAAT和GCCA，NUUU，其中N是任何前述的任何核苷酸或补体，其中所述单分子或双链多核苷酸长度为至少5个碱基对并且包含感觉 和至少基本上互补的反义区。

    MICRO-RNA SCAFFOLDS AND NON-NATURALLY OCCURRING MICRO-RNAS
    8.
    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。

    Highly functional short hairpin RNA
    9.
    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。