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1. 发明申请

US20060185027A1 Systems and methods for identifying miRNA targets and for altering miRNA and target expression 审中-公开
标题翻译：用于鉴定miRNA靶标和改变miRNA和靶标表达的系统和方法
公开(公告)号：US20060185027A1
公开(公告)日：2006-08-17
申请号：US11317660
申请日：2005-12-23
申请人： David Bartel , Benjamin Lewis , Matthew Jones-Rhoades , Christopher Burge
发明人： David Bartel , Benjamin Lewis , Matthew Jones-Rhoades , Christopher Burge
IPC分类号： A01K67/027 , A61K48/00 , G06F19/00 , C12N5/08 , C07H21/02
CPC分类号： C12N15/111 , C12N2310/14 , C12N2320/11
摘要： The present invention generally relates to microRNAs such as vertebrate microRNA (miRNA), for example, mammalian miRNA. Various aspects of the invention are directed to the detection, production, or expression of miRNA. In one aspect, the invention provides systems and methods for identifying targets of miRNA sequences. For instance, in one embodiment, gene sequences comprising UTRs are compared with miRNA sequences to determine the degree of interaction, for example, by determining a free energy measurement between the miRNA sequence and the UTR, and/or by determining complementarity between at least a portion of the miRNA sequence and the UTR. In another aspect, the invention is directed to the regulation of gene expression using miRNA. For example, gene expression within a cell may be altered by exposing the cell to an oligonucleotide comprising a sequence that is substantially antisense to at least a portion of an miRNA region of the gene, for example, antisense to a 6-mer or 7-mer portion of the miRNA. In still another aspect, the invention is directed to the treatment of cancer. For instance, in one set of embodiments, an isolated oligonucleotide comprising a sequence that is substantially antisense to an miRNA, or a portion of an miRNA, is administered to a subject having or being at risk of cancer. Yet other aspects of the invention are directed to compositions or kits including oligonucleotides comprising a sequence that is substantially antisense to an miRNA (or a portion of an miRNA), methods of promoting any of the above aspects, or the like.
摘要翻译：本发明通常涉及微小RNA，例如脊椎动物微小RNA（miRNA），例如哺乳动物miRNA。本发明的各个方面涉及miRNA的检测，产生或表达。一方面，本发明提供用于鉴定miRNA序列靶标的系统和方法。例如，在一个实施方案中，将包含UTR的基因序列与miRNA序列进行比较以确定相互作用程度，例如通过确定miRNA序列和UTR之间的自由能测量，和/或通过确定至少一个部分miRNA序列和UTR。另一方面，本发明涉及使用miRNA调节基因表达。例如，可以通过将细胞暴露于寡核苷酸来改变细胞内的基因表达，所述寡核苷酸包含基本上与基因的miRNA区的至少一部分反义的序列，例如与6-聚体或7- miRNA的部分。另一方面，本发明涉及癌症的治疗。例如，在一组实施方案中，将包含基本上与miRNA或一部分miRNA基本反义的序列的分离的寡核苷酸施用于具有或具有癌症风险的受试者。本发明的其它方面涉及包括寡核苷酸的组合物或试剂盒，其包含基本上与miRNA（或miRNA的一部分）反义的序列，促进任何上述方面的方法等。

2. 发明申请

US20070003962A1 RNA sequence-specific mediators of RNA interference 审中-公开
公开(公告)号：US20070003962A1
公开(公告)日：2007-01-04
申请号：US11474930
申请日：2006-06-26
申请人： Thomas Tuschl , Phillip Zamore , Phillip Sharp , David Bartel
发明人： Thomas Tuschl , Phillip Zamore , Phillip Sharp , David Bartel
IPC分类号： C12Q1/68 , C07H21/02 , C12P19/34
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.

3. 发明申请

US20070003961A1 RNA sequence-specific mediators of RNA interference 审中-公开
公开(公告)号：US20070003961A1
公开(公告)日：2007-01-04
申请号：US11474919
申请日：2006-06-26
申请人： Thomas Tuschl , Phillip Zamore , Phillip Sharp , David Bartel
发明人： Thomas Tuschl , Phillip Zamore , Phillip Sharp , David Bartel
IPC分类号： C12Q1/68
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.

4. 发明申请

US20070003963A1 RNA sequence-specific mediators of RNA interference 审中-公开
标题翻译： RNA干扰的RNA序列特异性介质
公开(公告)号：US20070003963A1
公开(公告)日：2007-01-04
申请号：US11474932
申请日：2006-06-26
申请人： Thomas Tuschl , Phillip Zamore , Phillip Sharp , David Bartel
发明人： Thomas Tuschl , Phillip Zamore , Phillip Sharp , David Bartel
IPC分类号： C12Q1/68 , C12N15/86
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 finction. 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。

5. 发明申请

US20050075492A1 Methods and products for expression of micro RNAs 有权
标题翻译：用于表达微RNA的方法和产品
公开(公告)号：US20050075492A1
公开(公告)日：2005-04-07
申请号：US10913288
申请日：2004-08-06
申请人： Chang-Zheng Chen , David Bartel , Harvey Lodish
发明人： Chang-Zheng Chen , David Bartel , Harvey Lodish
IPC分类号： C07H21/02 , C12N15/113
CPC分类号： C12N15/113 , C07H21/02 , C12N15/111 , C12N2310/111 , C12N2310/14 , C12N2310/141 , C12N2310/53 , C12N2310/531 , C12N2330/30 , C12N2330/51
摘要： The invention relates to microRNAs, methods of producing microRNAs and methods for using microRNAs.
摘要翻译：本发明涉及微小RNA，产生微小RNA的方法和使用微小RNA的方法。

6. 发明申请

US20050144669A1 MicroRNAs in plants 审中-公开
标题翻译：植物中的微RNA
公开(公告)号：US20050144669A1
公开(公告)日：2005-06-30
申请号：US10884374
申请日：2004-07-01
申请人： Brenda Reinhart , Earl Weinstein , Matthew Rhoades , Bonnie Bartel , David Bartel
发明人： Brenda Reinhart , Earl Weinstein , Matthew Rhoades , Bonnie Bartel , David Bartel
IPC分类号： C07H21/04 , C12N15/82 , C12N15/87
CPC分类号： C07H21/04 , C12N15/8218
摘要： The present invention generally relates to the production and expression of microRNA (miRNA) in plants. In some cases, production and expression of miRNA can be used to at least partially inhibit or alter gene expression in plants. For instance, in some embodiments, a nucleotide sequence, which may encode a sequence substantially complementary to a gene to be inhibited or otherwise altered, may be prepared and inserted into a plant cell. Expression of the nucleotide sequence may cause the formation of precursor miRNA, which may, in turn, be cleaved (for example, with Dicer or other nucleases, including, for example, nucleases associated with RNA interference), to produce an miRNA sequence substantially complementary to the gene. The miRNA sequence may then interact with the gene (e.g., complementary binding) to inhibit the gene. In some cases, the nucleotide sequence may be an isolated nucleotide sequence. Other embodiments of the invention are directed to the precursor miRNA and/or the final miRNA sequence, as well as methods of making, promoting, and use thereof.
摘要翻译：本发明一般涉及植物中微小RNA（miRNA）的产生和表达。在某些情况下，miRNA的产生和表达可用于至少部分抑制或改变植物中的基因表达。例如，在一些实施方案中，可以制备可以编码与待抑制或以其它方式改变的基因基本上互补的序列的核苷酸序列并将其插入植物细胞中。核苷酸序列的表达可能导致前体miRNA的形成，其可以依次被切割（例如，用Dicer或其它核酸酶，包括例如与RNA干扰相关的核酸酶），以产生基本上互补的miRNA序列到基因。然后，miRNA序列可以与基因（例如，互补结合）相互作用以抑制基因。在一些情况下，核苷酸序列可以是分离的核苷酸序列。本发明的其它实施方案涉及前体miRNA和/或最终miRNA序列，以及其制备，促进和使用方法。

7. 发明申请

US20050103242A1 Safe 有权
公开(公告)号：US20050103242A1
公开(公告)日：2005-05-19
申请号：US11022261
申请日：2004-12-23
申请人： David Bartel , Melvin Keehart
发明人： David Bartel , Melvin Keehart
IPC分类号： E05D15/58 , E05G1/00 , E05G1/026 , E05G1/04
CPC分类号： E05D15/56 , E05D15/58 , E05G1/00 , E05G1/026 , E05Y2900/20 , E05Y2900/602 , E06B3/5045
摘要： A safe having a support assembly disposed in the interior of the safe. The door of the safe is coupled to the support assembly and is shiftable between a closed position wherein the door is received in an opening of the safe and an open position wherein the door is removed from the opening in the safe and disposed in the interior of the safe.

8. 发明申请

US20120196924A1 METHODS AND PRODUCTS FOR EXPRESSION OF MICRO RNAs 有权
标题翻译：用于表达微RNA的方法和产品
公开(公告)号：US20120196924A1
公开(公告)日：2012-08-02
申请号：US13326506
申请日：2011-12-15
申请人： Chang-Zheng Chen , David Bartel , Harvey Lodish
发明人： Chang-Zheng Chen , David Bartel , Harvey Lodish
IPC分类号： A61K48/00 , C12N15/79 , A61P7/00 , C12N1/21 , C12N5/10 , C12N1/19 , C07H21/02 , C12N15/63
CPC分类号： C12N15/113 , C07H21/02 , C12N15/111 , C12N2310/111 , C12N2310/14 , C12N2310/141 , C12N2310/53 , C12N2310/531 , C12N2330/30 , C12N2330/51
摘要： The invention relates to microRNAs, methods of producing microRNAs and methods for using microRNAs.
摘要翻译：本发明涉及微小RNA，产生微小RNA的方法和使用微小RNA的方法。

9. 发明授权

US08106180B2 Methods and products for expression of micro RNAs 有权
标题翻译：用于表达微RNA的方法和产品
公开(公告)号：US08106180B2
公开(公告)日：2012-01-31
申请号：US10913288
申请日：2004-08-06
申请人： Chang-Zheng Chen , David Bartel , Harvey Lodish
发明人： Chang-Zheng Chen , David Bartel , Harvey Lodish
IPC分类号： C07H21/04
CPC分类号： C12N15/113 , C07H21/02 , C12N15/111 , C12N2310/111 , C12N2310/14 , C12N2310/141 , C12N2310/53 , C12N2310/531 , C12N2330/30 , C12N2330/51
摘要： The invention relates to microRNAs, methods of producing microRNAs and methods for using microRNAs.
摘要翻译：本发明涉及微小RNA，产生微小RNA的方法和使用微小RNA的方法。

10. 发明申请

US20100029003A1 System and methods for identifying miRNA targets and for altering miRNA and target expression 审中-公开
标题翻译：用于鉴定miRNA靶标和改变miRNA和靶标表达的系统和方法
公开(公告)号：US20100029003A1
公开(公告)日：2010-02-04
申请号：US12321489
申请日：2009-01-21
申请人： David Bartel , Benjamin P. Lewis , Matthew W. Jones-Rhoades , Christopher B. Burge
发明人： David Bartel , Benjamin P. Lewis , Matthew W. Jones-Rhoades , Christopher B. Burge
IPC分类号： C12N15/85
CPC分类号： C12N15/111 , C12N2310/14 , C12N2320/11
摘要： The present invention generally relates to microRNAs such as vertebrate microRNA (miRNA), for example, mammalian miRNA. Various aspects of the invention are directed to the detection, production, or expression of miRNA. In one aspect, the invention provides systems and methods for identifying targets of miRNA sequences. For instance, in one embodiment, gene sequences comprising UTRs are compared with miRNA sequences to determine the degree of interaction, for example, by determining a free energy measurement between the miRNA sequence and the UTR, and/or by determining complementarity between at least a portion of the miRNA sequence and the UTR. In another aspect, the invention is directed to the regulation of gene expression using miRNA. For example, gene expression within a cell may be altered by exposing the cell to an oligonucleotide comprising a sequence that is substantially antisense to at least a portion of an miRNA region of the gene, for example, antisense to a 6-mer or 7-mer portion of the miRNA. In still another aspect, the invention is directed to the treatment of cancer. For instance, in one set of embodiments, an isolated oligonucleotide comprising a sequence that is substantially antisense to an miRNA, or a portion of an miRNA, is administered to a subject having or being at risk of cancer. Yet other aspects of the invention are directed to compositions or kits including oligonucleotides comprising a sequence that is substantially antisense to an miRNA (or a portion of an miRNA), methods of promoting any of the above aspects, or the like.
摘要翻译：本发明通常涉及微小RNA，例如脊椎动物微小RNA（miRNA），例如哺乳动物miRNA。本发明的各个方面涉及miRNA的检测，产生或表达。一方面，本发明提供用于鉴定miRNA序列靶标的系统和方法。例如，在一个实施方案中，将包含UTR的基因序列与miRNA序列进行比较以确定相互作用程度，例如通过确定miRNA序列和UTR之间的自由能测量，和/或通过确定至少一个部分miRNA序列和UTR。另一方面，本发明涉及使用miRNA调节基因表达。例如，可以通过将细胞暴露于寡核苷酸来改变细胞内的基因表达，所述寡核苷酸包含基本上与基因的miRNA区的至少一部分反义的序列，例如与6-聚体或7- miRNA的部分。另一方面，本发明涉及癌症的治疗。例如，在一组实施方案中，将包含基本上与miRNA或一部分miRNA基本反义的序列的分离的寡核苷酸施用于具有或具有癌症风险的受试者。本发明的其它方面涉及包括寡核苷酸的组合物或试剂盒，其包含基本上与miRNA（或miRNA的一部分）反义的序列，促进任何上述方面的方法等。

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