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公开(公告)号：US08101348B2
公开(公告)日：2012-01-24
申请号：US10520470
申请日：2003-07-10
CPC分类号： C12N15/113 , A61K47/549 , A61K47/557 , C07K14/4705 , C07K19/00 , C12N15/111 , C12N2310/14 , C12N2310/351 , C12N2310/3513 , C12N2320/30 , C12N2320/51 , C12N2330/30
摘要： The present invention relates to sequence and structural features of single-stranded (ss) RNA molecules required to mediate target-specific nucleic acid modifications by RNA-interference (RNAi), such as target mRNA degradation and/or DNA methylation.
摘要翻译： 本发明涉及通过RNA干扰（RNAi）介导靶特异性核酸修饰所需的单链（ss）RNA分子的序列和结构特征，例如靶mRNA降解和/或DNA甲基化。
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公开(公告)号：US20060166910A1
公开(公告)日：2006-07-27
申请号：US10520470
申请日：2003-07-10
IPC分类号： A61K48/00
CPC分类号： C12N15/113 , A61K47/549 , A61K47/557 , C07K14/4705 , C07K19/00 , C12N15/111 , C12N2310/14 , C12N2310/351 , C12N2310/3513 , C12N2320/30 , C12N2320/51 , C12N2330/30
摘要： The present invention relates to sequence and structural features of single-stranded (ss) RNA molecules required to mediate target-specific nucleic acid modifications by RNA-interference (RNAi), such as target mRNA degradation and/or DNA methylation.
摘要翻译： 本发明涉及通过RNA干扰（RNAi）介导靶特异性核酸修饰所需的单链（ss）RNA分子的序列和结构特征，例如靶mRNA降解和/或DNA甲基化。
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3.发明授权公开(公告)号：US08470797B2
公开(公告)日：2013-06-25
申请号：US13438170
申请日：2012-04-03
申请人： Thomas Tuschl , Tilmann Achsel , Reinhard Luehrmann , Jutta Myer
发明人： Thomas Tuschl , Tilmann Achsel , Reinhard Luehrmann , Jutta Myer
IPC分类号： C12N15/11
CPC分类号： C12N15/111 , A01K2217/05 , A01K2217/075 , A61K38/00 , A61K48/0058 , C12N2310/111 , C12N2310/14 , C12N2310/53 , C12N2330/30
摘要： The invention relates to vectors for the inducible expression of RNA molecules in eukaryotic, particularly mammalian cells and transgenic animals.
摘要翻译： 本发明涉及用于在真核细胞，特别是哺乳动物细胞和转基因动物中可诱导表达RNA分子的载体。
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公开(公告)号：US08790922B2
公开(公告)日：2014-07-29
申请号：US12897759
申请日：2010-10-04
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。
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公开(公告)号：US08754203B2
公开(公告)日：2014-06-17
申请号：US13469689
申请日：2012-05-11
申请人： Thomas Tuschl , Pablo Landgraf
发明人： Thomas Tuschl , Pablo Landgraf
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。
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公开(公告)号：US08394628B2
公开(公告)日：2013-03-12
申请号：US12897744
申请日：2010-10-04
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.
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公开(公告)号：US08372968B2
公开(公告)日：2013-02-12
申请号：US12537602
申请日：2009-08-07
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.
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公开(公告)号：US08198428B2
公开(公告)日：2012-06-12
申请号：US12775952
申请日：2010-05-07
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和21个核苷酸RNA，其作为发育时间的关键调节剂。 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。
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公开(公告)号：US20120070892A1
公开(公告)日：2012-03-22
申请号：US13307694
申请日：2011-11-30
申请人： Sebastien Pfeffer , Thomas Tuschl
发明人： Sebastien Pfeffer , Thomas Tuschl
CPC分类号： C12N15/1131 , C07H21/04 , C07K14/005 , C12N15/111 , C12N2310/111 , C12N2310/14 , C12N2310/53 , C12N2320/11 , C12N2330/10 , C12N2330/31 , C12N2710/16022 , C12N2710/16222 , C12N2710/16422
摘要： The invention relates to isolated nucleic acid molecules comprising the sequence of a human cytomegalovirus microRNA. In another embodiment, the invention relates to single stranded DNA virus microRNA molecules comprising the sequence of a human cytomegalovirus microRNA. The invention also relates to the anti-DNA virus microRNA molecules.
摘要翻译： 本发明涉及包含人巨细胞病毒微RNA序列的分离的核酸分子。 在另一个实施方案中，本发明涉及包含人巨细胞病毒微RNA序列的单链DNA病毒微小RNA分子。 本发明还涉及抗DNA病毒微小RNA分子。
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公开(公告)号：US20120015042A1
公开(公告)日：2012-01-19
申请号：US13008636
申请日：2011-01-18
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.
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