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    RNA sequence-specific mediators of RNA interference
    1.
    发明公开
    RNA sequence-specific mediators of RNA interference 有权
    RNA-sequenzspezifische Mediatoren von RNA-Interferenz

    公开(公告)号：EP2028278A1

    公开(公告)日：2009-02-25

    申请号：EP08168152.0

    申请日：2001-03-30

    申请人： Whitehead Institute For Biomedical Research ,  Max-Planck-Gesellschaft zur Förderung der Wissenschaften e.V. ,  Massachusetts Institute of Technology ,  UNIVERSITY OF MASSACHUSETTS MEDICAL CENTER

    发明人： Tuschl, Thomas ,  Sharp, Phillip A. ,  Zamore, Phillip D. ,  Bartel, David P.

    IPC分类号： C12Q1/68 ,  C12N15/10

    CPC分类号： C12N15/113 ,  A01K67/0336 ,  A01K2207/05 ,  A01K2217/075 ,  A01K2227/703 ,  A01K2267/03 ,  A61K38/00 ,  C07H21/02 ,  C12N15/1079 ,  C12N15/111 ,  C12N2310/14 ,  C12N2310/321 ,  C12N2310/53 ,  C12N2330/30 ,  C12Q1/66 ,  C12N2310/3521

    摘要： The present invention relates to a Drosophila in vitro system which was used to demonstrate that dsRNA is processed to RNA segments 21-23 nucleotides (nt) in length. Furthermore, when these 21-23 nt fragments are purified and added back to Drosophila extracts, they mediate RNA interference in the absence of long dsRNA. Thus, these 21-23 nt fragments are the sequence-specific mediators of RNA degradation. A molecular signal, which may be their specific length, must be present in these 21-23 nt fragments to recruit cellular factors involved in RNAi. This present invention encompasses these 21-23 nt fragments and their use for specifically inactivating gene function. The use of these fragments (or chemically synthesized oligonucleotides of the same or similar nature) enables the targeting of specific mRNAs for degradation in mammalian cells, where the use of long dsRNAs to elicit RNAi is usually not practical, presumably because of the deleterious effects of the interferon response. This specific targeting of a particular gene function is useful in functional genomic and therapeutic applications.

    摘要翻译： 本发明涉及果蝇体外系统，其用于证明dsRNA被加工成长度为21-23个核苷酸（nt）的RNA片段。 此外，当这些21-23个片段被纯化并加回到果蝇提取物时，它们在不存在长dsRNA的情况下介导RNA干扰。 因此，这些21-23个片段是RNA降解的序列特异性介质。 必须在这21-23个片段中存在可能是其特异性长度的分子信号，以招募涉及RNAi的细胞因子。 本发明包括这些21-23个片段及其用于特异性灭活基因功能的用途。 这些片段（或相同或相似性质的化学合成寡核苷酸）的使用使得能够靶向用于在哺乳动物细胞中降解的特异性mRNA，其中使用长dsRNA引发RNAi通常是不实际的，可能是因为有害影响 干扰素反应。 特定基因功能的特异性靶向在功能基因组和治疗应用中是有用的。

    RNA sequence-specific mediators of RNA interference
    3.
    发明公开
    RNA sequence-specific mediators of RNA interference 有权
    一种用于通过RNA干扰的RNA的序列特异性介质的装置以及它们的用途制备敲除细胞或生物体过程

    公开(公告)号：EP2360253A1

    公开(公告)日：2011-08-24

    申请号：EP10184520.4

    申请日：2001-03-30

    申请人： The Whitehead Institute for Biomedical Research ,  Max-Planck-Gesellschaft zur Förderung der Wissenschaften e.V. ,  Massachusetts Institute of Technology ,  University of Massachusetts

    发明人： Tuschl, Thomas ,  Sharp, Phillip A. ,  Zamore, Phillip D. ,  Bartel, David P.

    IPC分类号： C12N15/113

    CPC分类号： C12N15/113 ,  A01K2217/075 ,  A61K9/0019 ,  A61K38/00 ,  A61K47/549 ,  A61K48/00 ,  C12N15/1079 ,  C12N15/111 ,  C12N2310/14 ,  C12N2310/321 ,  C12N2310/53 ,  C12N2330/30 ,  C12N2310/3521

    摘要： The present invention relates to a Drosophila in vitro system which was used to demonstrate that dsRNA is processed to RNA segments 21-23 nucleotides (nt) in length. Furthermore, when these 21-23 nt fragments are purified and added back to Drosophila extracts, they mediate RNA interference in the absence of long dsRNA. Thus, these 21-23 nt fragments are the sequence-specific mediators of RNA degradation. A molecular signal, which may be their specific length, must be present in these 21-23 nt fragments to recruit cellular factors involved in RNAi. This present invention encompasses these 21-23 nt fragments and their use for specifically inactivating gene function.; The use of these fragments (or chemically synthesized oligonucleotides of the same or similar nature) enables the targeting of specific mRNAs for degradation in mammalian cells, where the use of long dsRNAs to elicit RNAi is usually not practical, presumably because of the deleterious effects of the interferon response. This specific targeting of a particular gene function is useful in functional genomic and therapeutic applications.

    摘要翻译： 本发明涉及一种用于证明没dsRNA被加工成在长度RNA区段21-23个核苷酸（nt）的果蝇体外系统。 进一步，当合成21-23 nt的片段被纯化并加回至果蝇提取物，它们介导在不存在长dsRNA的RNA干扰。 因此，论文21-23个核苷酸的片段是RNA降解的序列特异性介质。 的分子信号，其可以是其具体的长度，必须存在于合成21-23个核苷酸的片段招募在RNAi中所涉及的细胞因子。 此本发明涵盖本文约21-23个碱基的片段及其用于特异性失活基因的功能使用。 使用合成片段（或具有相同或相似性质的化学合成的寡核苷酸）的启用特定的mRNA的靶向降解在哺乳动物细胞中，其中使用长dsRNA引发RNAi是一般不实际，可能的因为的有害影响 干扰素应答。 特定基因功能的这个特定的定位是在功能基因组和治疗应用。