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1. 发明申请

US20100273856A1 SCREENING OF MICRO-RNA CLUSTER INHIBITOR POOLS 有权
标题翻译：微RNA聚集体抑制剂池的筛选
公开(公告)号：US20100273856A1
公开(公告)日：2010-10-28
申请号：US12670363
申请日：2008-07-21
申请人： Anja Smith , Scott Baskerville , Devin Leake , Annaleen Vermeulen , Barbara Robertson , Anastasia Khvorova
发明人： Anja Smith , Scott Baskerville , Devin Leake , Annaleen Vermeulen , Barbara Robertson , Anastasia Khvorova
IPC分类号： A61K31/7105 , C12Q1/68 , C12N5/09 , A61P35/00
CPC分类号： C12N15/111 , C12N2310/113 , C12N2310/141 , C12N2320/12 , C12N2330/10 , C12Q1/6886 , C12Q2600/178
摘要： The disclosure provides methods for inhibiting the activity of a miRNA cluster in a cell, and also for screening a cell for a phenotype(s) of interest resulting from inhibition of a miRNA cluster. The methods use a cluster pool which comprises at least one miRNA inhibitor specific for each miRNA in the miRNA cluster. MiRNA inhibitors are described that induce apoptosis in breast cancer cells and hence are useful in the treatment of breast cancer. The disclosure also provides pharmaceutical compositions which are useful for the treatment of breast cancer; methods for inducing the nuclear translocation of NF-κB in a breast cancer cell; methods for inducing the nuclear translocation of c-Jun in a breast cancer cell; method for inhibiting the nuclear translocation of NF-κB in a breast cancer cell; and methods for providing prognostic medical information relating to breast cancer progression.
摘要翻译：本公开提供了抑制细胞中miRNA簇的活性的方法，以及用于筛选由miRNA群抑制引起的表型的细胞。该方法使用聚类池，其包含至少一种对miRNA簇中的每个miRNA特异的miRNA抑制剂。描述了诱导乳腺癌细胞凋亡的MiRNA抑制剂，因此可用于治疗乳腺癌。本公开还提供了可用于治疗乳腺癌的药物组合物; 在乳腺癌细胞中诱导NF-κB的核易位的方法; 在乳腺癌细胞中诱导c-Jun的核易位的方法; 抑制乳腺癌细胞中NF-κB的核易位的方法; 以及用于提供与乳腺癌进展相关的预后医学信息的方法。

2. 发明授权

US08367318B2 Screening of micro-RNA cluster inhibitor pools 有权
标题翻译：筛选微RNA聚类抑制剂池
公开(公告)号：US08367318B2
公开(公告)日：2013-02-05
申请号：US12670363
申请日：2008-07-21
申请人： Anja Smith , Scott Baskerville , Devin Leake , Annaleen Vermeulen , Barbara Robertson , Anastasia Khvorova
发明人： Anja Smith , Scott Baskerville , Devin Leake , Annaleen Vermeulen , Barbara Robertson , Anastasia Khvorova
IPC分类号： C12Q1/68
CPC分类号： C12N15/111 , C12N2310/113 , C12N2310/141 , C12N2320/12 , C12N2330/10 , C12Q1/6886 , C12Q2600/178
摘要： The disclosure provides methods for inhibiting the activity of a miRNA cluster in a cell, and also for screening a cell for a phenotype(s) of interest resulting from inhibition of a miRNA cluster. The methods use a cluster pool which comprises at least one miRNA inhibitor specific for each miRNA in the miRNA cluster. MiRNA inhibitors are described that induce apoptosis in breast cancer cells and hence are useful in the treatment of breast cancer. The disclosure also provides pharmaceutical compositions which are useful for the treatment of breast cancer; methods for inducing the nuclear translocation of NF-κB in a breast cancer cell; methods for inducing the nuclear translocation of c-Jun in a breast cancer cell; method for inhibiting the nuclear translocation of NF-κB in a breast cancer cell; and methods for providing prognostic medical information relating to breast cancer progression.
摘要翻译：本公开提供了抑制细胞中miRNA簇的活性的方法，以及用于筛选由miRNA群抑制引起的表型的细胞。该方法使用聚类池，其包含至少一种对miRNA簇中的每个miRNA特异的miRNA抑制剂。描述了诱导乳腺癌细胞凋亡的MiRNA抑制剂，因此可用于治疗乳腺癌。本公开还提供了可用于治疗乳腺癌的药物组合物; 在乳腺癌细胞中诱导NF-κB的核易位的方法; 在乳腺癌细胞中诱导c-Jun的核易位的方法; 抑制乳腺癌细胞中NF-κB的核易位的方法; 以及用于提供与乳腺癌进展相关的预后医学信息的方法。

3. 发明申请

US20100184209A1 COMPOSITIONS AND METHODS FOR INHIBITING GENE SILENCING BY RNA INTERFERENCE 审中-公开
标题翻译：通过RNA干扰抑制基因沉默的组合物和方法
公开(公告)号：US20100184209A1
公开(公告)日：2010-07-22
申请号：US12279594
申请日：2007-02-16
申请人： Annaleen Vermeulen , Barbara Robertson , Scott Baskerville , Christina Yamada , Devin Leake , Yuriy Fedorov , Jon Karpilow , Anastasia Khvorova
发明人： Annaleen Vermeulen , Barbara Robertson , Scott Baskerville , Christina Yamada , Devin Leake , Yuriy Fedorov , Jon Karpilow , Anastasia Khvorova
IPC分类号： C12N5/071 , C07H21/02
CPC分类号： C12N15/111 , C12N15/113 , C12N2310/11 , C12N2310/321 , C12N2310/3515 , C12N2310/53 , C12N2320/50 , C12N2310/3521
摘要： The present invention provides compositions and methods for inhibiting gene silencing by the RNAi pathway. The RNAi inhibitors of the invention have a reverse complement (RC) region to the target molecule of interest (e.g., miRNA) in association with at least one flanking region coupled to either at the 3′ or 5′ end of the RC region. The flanking regions can be single-stranded or can have one or more regions of double stranded nucleic acid with or without a hairpin loop. The RNAi inhibitors described herein can inhibit endogenous targets, including but not limited to microRNAs, or piRNAs, or can be used to inhibit the effects of exogenously introduced molecules, such as synthetic siRNAs, siRNAs expressed from vector constructs (e.g., viral expression systems), or siRNAs generated by enzymatic methods. Inhibition is specific, potent, prolonged, and can be performed on a single target or multiple targets simultaneously.
摘要翻译：本发明提供了通过RNAi途径抑制基因沉默的组合物和方法。本发明的RNAi抑制剂与至少一个与RC区的3'或5'末端连接的侧翼区域具有与目的靶分子（例如miRNA）的反向互补序列（RC）区域。侧翼区域可以是单链的或可以具有一个或多个具有或不具有发夹环的双链核酸区域。本文所述的RNAi抑制剂可抑制内源性靶标，包括但不限于微小RNA或piRNA，或可用于抑制外源引入分子如合成siRNAs，由载体构建体（例如病毒表达系统）表达的siRNA的作用，，或通过酶法产生的siRNA。抑制是具体的，有效的，延长的，并且可以同时在单个靶或多个靶上进行。

4. 发明申请

US20080009012A1 Methods, libraries and computer program products for determining whether siRNA induced phenotypes are due to off-target effects 审中-公开
标题翻译：用于确定siRNA诱导表型的方法，文库和计算机程序产品是否由于脱靶效应
公开(公告)号：US20080009012A1
公开(公告)日：2008-01-10
申请号：US11825461
申请日：2007-07-06
申请人： Amanda Birmingham , Emily Anderson , Angela Reynolds , Devin Leake , Scott Baskerville , Yuriy Fedorov , Jon Karpilow , William Marshall , Anastasia Khvorova
发明人： Amanda Birmingham , Emily Anderson , Angela Reynolds , Devin Leake , Scott Baskerville , Yuriy Fedorov , Jon Karpilow , William Marshall , Anastasia Khvorova
IPC分类号： C12Q1/68 , C07H21/04
CPC分类号： C12N15/111 , C12N2310/14 , C12N2320/50 , C12N2330/31
摘要： The present disclosure provides methods, libraries and computer program products for determining whether a phenotype induced by a candidate siRNA for a target gene in an RNAi experiment is target specific or a false positive. Through the use of a control siRNA that has one or two seed sequences of six or seven bases in combination with a neutral scaffolding sequence, a distinction can be made between false positive and true positive analyses of functionality.
摘要翻译：本公开提供了用于确定由RNAi实验中的靶基因的候选siRNA诱导的表型是靶标特异性还是假阳性的方法，文库和计算机程序产品。通过使用具有6个或7个碱基的一个或两个种子序列与中性脚手架序列组合的对照siRNA，可以区分功能性的假阳性和真阳性分析。

5. 发明申请

US20070218495A1 Methods, libraries and computer program products for gene silencing with reduced off-target effects 审中-公开
标题翻译：用于基因沉默的方法，图书馆和计算机程序产品，减少脱靶效应
公开(公告)号：US20070218495A1
公开(公告)日：2007-09-20
申请号：US11724346
申请日：2007-03-15
申请人： Amanda Birmingham , Emily Anderson , Angela Reynolds , Devin Leake , Scott Baskerville , Yuriy Fedorov , Jon Karpilow , William Marshall , Anastasia Khvorova
发明人： Amanda Birmingham , Emily Anderson , Angela Reynolds , Devin Leake , Scott Baskerville , Yuriy Fedorov , Jon Karpilow , William Marshall , Anastasia Khvorova
IPC分类号： C40B40/08 , C07H21/02
CPC分类号： C12N15/111 , C12N2310/14 , C12N2320/50 , C12N2330/31
摘要： The present invention provides methods, libraries and computer program products for selecting siRNA that reduce off-target effects and methods for gene silencing using these siRNAs. By comparing nucleotide sequences at positions 2-7 or 2-8 of the sense and/or antisense regions of candidate siRNAs to the 3′ UTR region of mRNAs, one can select siRNAs that have reduced off-target effects.
摘要翻译：本发明提供用于选择减少脱靶效应的siRNA的方法，文库和计算机程序产品以及使用这些siRNA的基因沉默方法。通过将候选siRNAs的有义和/或反义区的2-7位或2-8位的核苷酸序列与mRNA的3'UTR区进行比较，可以选择具有降低的脱靶效应的siRNA。

6. 发明申请

US20110160285A1 IDENTIFICATION OF MIRNA PROFILES THAT ARE DIAGNOSTIC OF HYPERTROPHIC CARDIOMYOPATHY 审中-公开
标题翻译：鉴别诊断超声心动图的MIRNA轮廓
公开(公告)号：US20110160285A1
公开(公告)日：2011-06-30
申请号：US12921827
申请日：2009-03-12
申请人： Emily Anderson , Anastasia Khvorova , Anita G. Seto , Scott Baskerville , Leslie Leinwand , Kevin G. Sullivan
发明人： Emily Anderson , Anastasia Khvorova , Anita G. Seto , Scott Baskerville , Leslie Leinwand , Kevin G. Sullivan
IPC分类号： A61K31/7105 , C40B30/04 , A61P9/00
CPC分类号： C12Q1/6883 , A61K48/00 , C12Q2600/178
摘要： Disclosed herein are a collection of miRNAs and genes whose expression is altered in hypertrophic cardiomyopathy. Accordingly, these miRNAs and genes, singly or in combination, are useful as molecular markers for diagnosis or prognosis of hypertrophic cardiomyopathy. The miRNAs and genes disclosed can also be therapeutic targets for cardiac hypertrophy. For example, agents such as miRNA mimics, miRNA inhibitors or siRNAs for a given miRNA or gene can be used to modulate the level of these molecules thereby inhibiting or preventing hypertrophic cardiomyopathy.
摘要翻译：本文公开了在增生性心肌病中表达改变的miRNA和基因的集合。因此，这些miRNA和基因单独或组合可用作增生性心肌病的诊断或预后的分子标记物。所公开的miRNA和基因也可以是心脏肥大的治疗靶点。例如，可以使用诸如miRNA模拟物，miRNA抑制剂或用于给定miRNA或基因的siRNA的试剂来调节这些分子的水平，从而抑制或预防肥大性心肌病。

7. 发明申请

US20090221435A1 MICROARRAY FOR DETECTING AND QUANTIFYING MICRORNA 审中-公开
标题翻译：用于检测和定量MICRORNA的微阵列
公开(公告)号：US20090221435A1
公开(公告)日：2009-09-03
申请号：US12278395
申请日：2007-02-07
申请人： Scott Baskerville , Fiona M. Jucker , Anastasia Khvorova
发明人： Scott Baskerville , Fiona M. Jucker , Anastasia Khvorova
IPC分类号： C40B30/04 , C40B40/06
CPC分类号： C12Q1/6837 , C12Q2525/207 , C12Q2525/197 , C12Q2525/161 , C12Q2537/163 , C12Q2565/525
摘要： A microarray can be configured for hybridizing with short nucleic acids, such as miRNA or siRNA, contained within a sample. Such a microarray includes a polynucleotide trap coupled to a substrate of a microarray site. The polynucleotide trap includes a probe that selectively hybridizes with short nucleic acid sequences, and a linker that is coupled to the substrate and configured to extend the probe from the substrate. Additionally, the polynucleotide trap can include an enhancer that hybridizes with the linker in order to enhance functionality of the probe. The linker and/or enhancer are configured to inhibit the probe from interacting with the linker or substrate. This can include the linker and/or enhancer being configured to have a minimal secondary structure so as to present the probe region for hybridizing with the target polynucleotide and inhibit the linker region or probe region from interacting with the substrate.
摘要翻译：可将微阵列配置为与样品中包含的短核酸如miRNA或siRNA杂交。这样的微阵列包括耦合到微阵列位点的底物的多核苷酸捕获物。多核苷酸捕获器包括与短核酸序列选择性杂交的探针和连接到基底并被配置为从基底延伸探针的接头。另外，多核苷酸捕获可以包括与接头杂交以增强探针的功能的增强子。接头和/或增强子被配置为抑制探针与接头或底物相互作用。这可以包括被配置为具有最小二级结构的接头和/或增强子，以便呈现用于与靶多核苷酸杂交的探针区域并且抑制接头区域或探针区域与底物相互作用。

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