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    IDENTIFICATION OF NOVEL GENES CODING FOR SMALL TEMPORAL RNAS
    52.
    发明申请
    IDENTIFICATION OF NOVEL GENES CODING FOR SMALL TEMPORAL RNAS 审中-公开
    鉴定小时RNAs的新基因编码

    公开(公告)号：US20130245090A1

    公开(公告)日：2013-09-19

    申请号：US13472826

    申请日：2012-05-16

    申请人： Thomas Tuschl ,  Mariana Lagos-Quintana ,  Winfried Lendeckel ,  Jutta Meyer ,  Reinhard Rauhut

    发明人： Thomas Tuschl ,  Mariana Lagos-Quintana ,  Winfried Lendeckel ,  Jutta Meyer ,  Reinhard Rauhut

    IPC分类号： C12N15/113

    CPC分类号： C12N15/113 ,  A61K38/00 ,  C12N2310/14 ,  C12N2310/141 ,  C12N2310/53 ,  C12N2330/10 ,  C12Q1/6876 ,  C12Q2600/136 ,  C12Q2600/178

    摘要： In Caenorhabditis elegans, lin-4 and let-7 enclode 22- and 21-nucleotide RNAs, respectively, that function as key regulators of developmental timing. Because the appearance of these short RNAs is regulated during development, they are also referred to as “small temporal RNAs” (stRNAs). We show that many more 21- and 22-nt expressed RNAs, termed microRNAs, (miRNAs), exist in invertebrates and vertebrates, and that some of these novel RNAs, similar to let-7 stRAN, are also highly conserved. This suggests that sequence-specific post-transcriptional regulatory mechanisms mediated by small RNAs are more general than previously appreciated.

    摘要翻译： 在秀丽隐杆线虫中，lin-4和let-7分别包含22个和21个核苷酸的RNA，其作为发育时机的关键调节剂。 因为这些短RNA的出现在发育过程中被调节，所以它们也被称为“小时间RNA”（stRNA）。 我们显示，更多的21和22-nt表达的RNA，称为microRNA（miRNA），存在于无脊椎动物和脊椎动物中，并且与let-7 stRAN相似的这些新型RNA中的一些也是高度保守的。 这表明由小RNA介导的序列特异性转录后调控机制比以前赞赏更为普遍。

    RNA interference mediating small RNA molecules
    53.
    发明授权
    RNA interference mediating small RNA molecules 有权
    RNA干扰介导小RNA分子

    公开(公告)号：US08445237B2

    公开(公告)日：2013-05-21

    申请号：US12834311

    申请日：2010-07-12

    申请人： Thomas Tuschl ,  Sayda Mahgoub Elbashir ,  Winfried Lendeckel

    发明人： Thomas Tuschl ,  Sayda Mahgoub Elbashir ,  Winfried Lendeckel

    IPC分类号： C12P19/34 ,  C12Q1/68 ,  C07H21/02 ,  A61K48/00

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

    摘要： Double-stranded RNA (dsRNA) induces sequence-specific post-transcriptional gene silencing in many organisms by a process known as RNA interference (RNAi). Using a Drosophila in vitro system, we demonstrate that 19-23 nt short RNA fragments are the sequence-specific mediators of RNAi. The short interfering RNAs (siRNAs) are generated by an RNase III-like processing reaction from long dsRNA. Chemically synthesized siRNA duplexes with overhanging 3′ ends mediate efficient target RNA cleavage in the lysate, and the cleavage site is located near the center of the region spanned by the guiding siRNA. Furthermore, we provide evidence that the direction of dsRNA processing determines whether sense or antisense target RNA can be cleaved by the produced siRNP complex.

    摘要翻译： 双链RNA（dsRNA）通过称为RNA干扰（RNAi）的过程在许多生物体中诱导序列特异性转录后基因沉默。 使用果蝇体外系统，我们证明19-23短小RNA片段是RNAi的序列特异性介质。 通过来自长dsRNA的RNA酶III类加工反应产生短干扰RNA（siRNA）。 与突出的3'端的化学合成的siRNA双链体介导裂解物中有效的靶RNA切割，并且切割位点位于由引导siRNA跨越的区域的中心附近。 此外，我们提供证据表明dsRNA加工的方向决定了有义或反义的靶RNA是否可以被生成的siRNP复合物切割。

    Human microRNAs and methods for inhibiting same
    56.
    发明授权
    Human microRNAs and methods for inhibiting same 有权
    人类微小RNA及其抑制方法

    公开(公告)号：US08247543B2

    公开(公告)日：2012-08-21

    申请号：US11919393

    申请日：2006-05-01

    申请人： Thomas Tuschl ,  Pablo Landgraf

    发明人： Thomas Tuschl ,  Pablo Landgraf

    IPC分类号： C07H21/04 ,  C07H21/02 ,  C12N15/63

    CPC分类号： C12N15/113 ,  C12N2310/14 ,  C12N2330/10

    摘要： The invention relates to isolated DNA or RNA molecules comprising at least ten contiguous bases having a sequence in a microRNA shown in SEQ ID NOs: 1-94; 281-374; 467-481; 497-522; or 549, except that up to thirty percent of the bases may be wobble bases, and up to 10% of the contiguous bases may be non-complementary. The invention further relates to modified single stranded microRNA molecules, isolated single stranded anti-microRNA molecules and isolated microRNP molecules. In another embodiment, the invention relates to a method for inhibiting microRNP activity in a cell.

    摘要翻译： 本发明涉及分离的DNA或RNA分子，其包含至少10个具有SEQ ID NO：1-94所示的微小RNA中的序列的连续碱基; 281-374; 467-481; 497-522; 或549，除了多达30％的碱基可以是摆动碱基，并且多达10％的连续碱基可以是非互补的。 本发明还涉及修饰的单链microRNA分子，分离的单链抗微RNA分子和分离的microRNP分子。 在另一个实施方案中，本发明涉及抑制细胞中microRNP活性的方法。

    RNA SEQUENCE-SPECIFIC MEDIATORS OF RNA INTERFERENCE
    57.
    发明申请
    RNA SEQUENCE-SPECIFIC MEDIATORS OF RNA INTERFERENCE 有权
    RNA干扰RNA序列特异性介质

    公开(公告)号：US20120029061A1

    公开(公告)日：2012-02-02

    申请号：US12897740

    申请日：2010-10-04

    申请人： Thomas Tuschl ,  Phillip D. Zamore ,  Phillip A. Sharp ,  David P. Bartel

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

    IPC分类号： A61K31/713 ,  C07H21/02

    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失活基因功能的用途。 使用这些片段（或具有相同或相似性质的化学合成的寡核苷酸）使得能够靶向用于哺乳动物细胞降解的特异性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。