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1. 发明申请

US20070149468A1 Methods and compositions for rna interference 有权
标题翻译： rna干扰的方法和组成
公开(公告)号：US20070149468A1
公开(公告)日：2007-06-28
申请号：US10557219
申请日：2004-05-17
申请人： Aimee Jackson , Steven Bartz , Julja Burchard , Janell Schelter , Peter Linsley
发明人： Aimee Jackson , Steven Bartz , Julja Burchard , Janell Schelter , Peter Linsley
IPC分类号： A61K48/00 , C12Q1/68
CPC分类号： C12N15/1137 , C12N15/1138 , C12N2310/14 , C12N2320/10 , C12N2320/12
摘要： The invention provides methods and compositions for gene silencing by RNA interference. In particular, the invention provides methods for gene silencing or RNA knockdown using small interfering RNAs (siRNAs) having partial sequence homology to its target gene. The invention also provides methods for identifying common and/or differential responses to a plurality of different siRNAs targeting a gene. The invention also provides methods for evaluating the relative activity of the two strands of an siRNA. The invention further provides methods of designing siRNAs for gene silencing. The invention further provides methods of using siRNAs as therapeutics for treatment of diseases.
摘要翻译：本发明提供了通过RNA干扰进行基因沉默的方法和组合物。特别地，本发明提供了使用与其靶基因具有部分序列同源性的小干扰RNA（siRNA）进行基因沉默或RNA敲低的方法。本发明还提供了鉴定针对基因的多种不同siRNA的常见和/或差异应答的方法。本发明还提供了评估siRNA两条链的相对活性的方法。本发明还提供了设计用于基因沉默的siRNA的方法。本发明还提供了使用siRNA作为治疗疾病的治疗剂的方法。

2. 发明授权

US09200275B2 Methods and compositions for regulating cell cycle progression 有权
标题翻译：用于调节细胞周期进程的方法和组合物
公开(公告)号：US09200275B2
公开(公告)日：2015-12-01
申请号：US12304968
申请日：2007-06-14
申请人： Peter S. Linsley , Janell Schelter , Julja Burchard , Lee Lim , Miho Kibukawa
发明人： Peter S. Linsley , Janell Schelter , Julja Burchard , Lee Lim , Miho Kibukawa
IPC分类号： C12N15/113 , C12N15/11
CPC分类号： C12N15/111 , C12N2310/14 , C12N2320/12 , C12N2330/10 , C12N2330/31
摘要： In one aspect, a method is provided of inhibiting proliferation of a mammalian cell comprising introducing into said cell an effective amount of at least one at least one small interfering RNA agent (iRNA), wherein said iRNA comprises a nucleotide sequence of at least 15 nucleotides, wherein the nucleotide sequence comprises a seed region consisting of nucleotide positions 1 to 12, wherein position 1 represents the 5′ end of the iRNA nucleotide sequence and wherein said seed region comprises a nucleotide sequence of at least six contiguous nucleotides that is complementary to six contiguous nucleotides within positions 1 to 12 of a nucleotide sequence, wherein position 1 represents the 5″end of the nucleotide sequence, wherein the nucleotide sequence is selected from the group consisting of SEQ ID NO: 1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7 and SEQ ID NO:8. In some embodiments, the method comprises introducing at least one iRNA that inhibits the expression of at least one miR-16 responsive gene selected from TABLE 5 into the mammalian cell.
摘要翻译：一方面，提供抑制哺乳动物细胞增殖的方法，包括向所述细胞中引入有效量的至少一种至少一种小干扰RNA试剂（iRNA），其中所述iRNA包含至少15个核苷酸的核苷酸序列，其中所述核苷酸序列包含由核苷酸位置1至12组成的种子区，其中位置1表示iRNA核苷酸序列的5'末端，并且其中所述种子区包含与六个互补的至少六个连续核苷酸的核苷酸序列核苷酸序列的第1至12位的连续核苷酸，其中位置1代表核苷酸序列的5“末端，其中所述核苷酸序列选自SEQ ID NO：1，SEQ ID NO：2，SEQ ID NO： NO：3，SEQ ID NO：4，SEQ ID NO：5，SEQ ID NO：6，SEQ ID NO：7和SEQ ID NO：8。在一些实施方案中，所述方法包括将至少一种抑制至少一种选自表5的miR-16应答基因的表达的iRNA引入到哺乳动物细胞中。

3. 发明申请

US20100035966A1 METHODS AND COMPOSITIONS FOR REGULATING CELL CYCLE PROGRESSION 有权
标题翻译：用于调节细胞周期进程的方法和组合物
公开(公告)号：US20100035966A1
公开(公告)日：2010-02-11
申请号：US12304968
申请日：2007-06-14
申请人： Peter S. Linsley , Janell Schelter , Julja Burchard , Lee Lim , Miho Kibukawa
发明人： Peter S. Linsley , Janell Schelter , Julja Burchard , Lee Lim , Miho Kibukawa
IPC分类号： A61K31/7105 , C12N5/10 , C12Q1/68 , C07H21/02
CPC分类号： C12N15/111 , C12N2310/14 , C12N2320/12 , C12N2330/10 , C12N2330/31
摘要： In one aspect, a method is provided of inhibiting proliferation of a mammalian cell comprising introducing into said cell an effective amount of at least one at least one small interfering RNA agent (iRNA), wherein said iRNA comprises a nucleotide sequence of at least 15 nucleotides, wherein the nucleotide sequence comprises a seed region consisting of nucleotide positions 1 to 12, wherein position 1 represents the 5′ end of the iRNA nucleotide sequence and wherein said seed region comprises a nucleotide sequence of at least six contiguous nucleotides that is complementary to six contiguous nucleotides within positions 1 to 12 of a nucleotide sequence, wherein position 1 represents the 5″end of the nucleotide sequence, wherein the nucleotide sequence is selected from the group consisting of SEQ ID NO: 1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7 and SEQ ID NO:8. In some embodiments, the method comprises introducing at least one iRNA that inhibits the expression of at least one miR-16 responsive gene selected from TABLE 5 into the mammalian cell.
摘要翻译：一方面，提供抑制哺乳动物细胞增殖的方法，包括向所述细胞中引入有效量的至少一种至少一种小干扰RNA试剂（iRNA），其中所述iRNA包含至少15个核苷酸的核苷酸序列，其中所述核苷酸序列包含由核苷酸位置1至12组成的种子区，其中位置1表示iRNA核苷酸序列的5'末端，并且其中所述种子区包含与六个互补的至少六个连续核苷酸的核苷酸序列其中位置1代表核苷酸序列的5'末端，其中所述核苷酸序列选自SEQ ID NO：1，SEQ ID NO：2，SEQ ID NO：2 SEQ ID NO：3，SEQ ID NO：4，SEQ ID NO：5，SEQ ID NO：6，SEQ ID NO：7和SEQ ID NO：8。在一些实施方案中，所述方法包括将至少一种抑制至少一种选自表5的miR-16应答基因的表达的iRNA引入到哺乳动物细胞中。

4. 发明申请

US20100227909A1 COMPOSITIONS COMPRISING MIR34 THERAPEUTIC AGENTS FOR TREATING CANCER 有权
标题翻译：包含MIR34治疗癌症治疗剂的组合物
公开(公告)号：US20100227909A1
公开(公告)日：2010-09-09
申请号：US12598590
申请日：2008-05-05
申请人： Michele A. Cleary , Aimee L. Jackson , Peter S. Linsley , Julja Burchard , Lee P. Lim , Jill F. Magnus
发明人： Michele A. Cleary , Aimee L. Jackson , Peter S. Linsley , Julja Burchard , Lee P. Lim , Jill F. Magnus
IPC分类号： A61K31/713 , C07H21/02 , A61P35/00
CPC分类号： C12N15/113 , C12N15/111 , C12N2310/14 , C12N2310/141 , C12N2320/53 , C12Q1/6886 , C12Q2600/136 , C12Q2600/158 , C12Q2600/178
摘要： In one aspect, the invention generally relates to compositions comprising miR-34 and siRNAs functionally and structurally related to miR-34 for the treatment of cancer.
摘要翻译：一方面，本发明一般涉及包含miR-34和在功能上和结构上与用于治疗癌症的miR-34相关的siRNA的组合物。

5. 发明申请

US20140088937A1 Methods of Predicting The Probability of Modulation of Transcript Levels By RNAI Compounds 审中-公开
标题翻译：通过RNAI化合物预测转录水平调节概率的方法
公开(公告)号：US20140088937A1
公开(公告)日：2014-03-27
申请号：US14091459
申请日：2013-11-27
申请人： Duncan Brown , Julja Burchard , Eugen C. Buehler
发明人： Duncan Brown , Julja Burchard , Eugen C. Buehler
IPC分类号： G06F19/12
CPC分类号： G16B5/00 , G16B20/00
摘要： The present invention provides a method for determining the probability that an RNAi compound modulates the expression level of a gene using a linear regression model. The present invention also provides a method for determining the probabilities that an RNAi compound modulates the expression levels of each gene in a set of genes of interest using the linear regression model. The present invention provides a method for determining the seed-sequence-dependent signature size of an RNAi compound using the linear regression model. The invention provides a method for identifying genes having seed-sequence-dependent silencing effect by an siRNA using the linear regression model. The invention further provides a method for selecting from a plurality of siRNAs one or more siRNAs with higher silencing efficacy, specificity and diversity in silencing a target gene in an organism. The invention also provides a method for determining the coefficients of the above linear regression model.
摘要翻译：本发明提供了使用线性回归模型确定RNAi化合物调节基因表达水平的可能性的方法。本发明还提供了使用线性回归模型确定RNAi化合物调节一组感兴趣基因中的每个基因的表达水平的概率的方法。本发明提供了使用线性回归模型确定RNAi化合物的种子序列依赖性特征大小的方法。本发明提供一种使用线性回归模型鉴定siRNA的具有种子序列依赖性沉默效应的基因的方法。本发明还提供了从多个siRNA中选择一种或多种沉默效力，特异性和沉默生物体中靶基因多样性的siRNA的方法。本发明还提供了一种用于确定上述线性回归模型的系数的方法。

6. 发明申请

US20120072123A1 Methods of Predicting The Probability of Modulation of Transcript Levels By RNAI Compounds 审中-公开
标题翻译：通过RNAI化合物预测转录水平调节概率的方法
公开(公告)号：US20120072123A1
公开(公告)日：2012-03-22
申请号：US13322931
申请日：2010-05-27
申请人： Duncan Brown , Julja Burchard , Eugen C. Buehler
发明人： Duncan Brown , Julja Burchard , Eugen C. Buehler
IPC分类号： G06F19/20
CPC分类号： G16B5/00 , G16B20/00
摘要： The present invention provides a method for determining the probability that an RNAi compound modulates the expression level of a gene using a linear regression model. The present invention also provides a method for determining the probabilities that an RNAi compound modulates the expression levels of each gene in a set of genes of interest using the linear regression model. The present invention provides a method for determining the seed-sequence-dependent signature size of an RNAi compound using the linear regression model. The invention provides a method for identifying genes having seed-sequence-dependent silencing effect by an siRNA using the linear regression model. The invention further provides a method for selecting from a plurality of siRNAs one or more siRNAs with higher silencing efficacy, specificity and diversity in silencing a target gene in an organism. The invention also provides a method for determining the coefficients of the above linear regression model.
摘要翻译：本发明提供了使用线性回归模型确定RNAi化合物调节基因表达水平的可能性的方法。本发明还提供了使用线性回归模型确定RNAi化合物调节一组感兴趣基因中的每个基因的表达水平的概率的方法。本发明提供了使用线性回归模型确定RNAi化合物的种子序列依赖性特征大小的方法。本发明提供一种使用线性回归模型鉴定siRNA的具有种子序列依赖性沉默效应的基因的方法。本发明还提供了从多个siRNA中选择一种或多种沉默效力，特异性和沉默生物体中靶基因多样性的siRNA的方法。本发明还提供了一种用于确定上述线性回归模型的系数的方法。

7. 发明授权

US08609830B2 Methods and compositions for RNA interference 有权
标题翻译： RNA干扰的方法和组成
公开(公告)号：US08609830B2
公开(公告)日：2013-12-17
申请号：US10557219
申请日：2004-05-17
申请人： Aimee L. Jackson , Steven R. Bartz , Julja Burchard , Janell M. Schelter , Peter S. Linsley
发明人： Aimee L. Jackson , Steven R. Bartz , Julja Burchard , Janell M. Schelter , Peter S. Linsley
IPC分类号： C07H21/00
CPC分类号： C12N15/1137 , C12N15/1138 , C12N2310/14 , C12N2320/10 , C12N2320/12
摘要： The invention provides methods and compositions for gene silencing by RNA interference. In particular, the invention provides methods for gene silencing or RNA knockdown using small interfering RNAs (siRNAs) having partial sequence homology to its target gene. The invention also provides methods for identifying common and/or differential responses to a plurality of different siRNAs targeting a gene. The invention also provides methods for evaluating the relative activity of the two strands of an siRNA. The invention further provides methods of designing siRNAs for gene silencing. The invention further provides methods of using siRNAs as therapeutics for treatment of diseases.
摘要翻译：本发明提供了通过RNA干扰进行基因沉默的方法和组合物。特别地，本发明提供了使用与其靶基因具有部分序列同源性的小干扰RNA（siRNA）进行基因沉默或RNA敲低的方法。本发明还提供了鉴定针对基因的多种不同siRNA的常见和/或差异应答的方法。本发明还提供了评估siRNA两条链的相对活性的方法。本发明还提供了设计用于基因沉默的siRNA的方法。本发明还提供了使用siRNA作为治疗疾病的治疗剂的方法。

8. 发明授权

US07962316B2 Method of designing siRNAs for gene silencing 有权
标题翻译：设计siRNA用于基因沉默的方法
公开(公告)号：US07962316B2
公开(公告)日：2011-06-14
申请号：US10577696
申请日：2004-10-27
申请人： Aimee L. Jackson , Steven R. Bartz , Julja Burchard , Peter S. Linsley , Wei Ge , Guy L. Cavet
发明人： Aimee L. Jackson , Steven R. Bartz , Julja Burchard , Peter S. Linsley , Wei Ge , Guy L. Cavet
IPC分类号： G06F17/10 , G06F7/60
CPC分类号： C12N15/111 , C12N2310/14 , C12N2320/11 , C12N2330/31 , G06F19/18 , G06F19/22
摘要： The present invention provides a method for identifying siRNA target motifs in a transcript using a position-specific score matrix approach. The invention also provides a method for identifying off-target genes of an siRNA using a position-specific score matrix approach. The invention further provides a method for designing siRNAs with higher silencing efficacy and specificity. The invention also provides a library of siRNAs comprising siRNAs with high silencing efficacy and specificity.
摘要翻译：本发明提供使用位置特异性评分矩阵法来鉴定转录物中的siRNA靶基序的方法。本发明还提供了一种使用位置特异性评分矩阵方法鉴定siRNA的靶外基因的方法。本发明还提供了设计具有较高沉默功效和特异性的siRNA的方法。本发明还提供了包含具有高沉默功效和特异性的siRNA的siRNA文库。

9. 发明授权

US07013221B1 Iterative probe design and detailed expression profiling with flexible in-situ synthesis arrays 有权
标题翻译：迭代探针设计和具有灵活原位合成阵列的详细表达谱
公开(公告)号：US07013221B1
公开(公告)日：2006-03-14
申请号：US09561487
申请日：2000-04-28
申请人： Stephen H. Friend , Roland Stoughton , Peter S. Linsley , Julja Burchard
发明人： Stephen H. Friend , Roland Stoughton , Peter S. Linsley , Julja Burchard
IPC分类号： G01N33/48 , C12Q1/68
CPC分类号： G06F19/20
摘要： Methods and compositions are provided that are useful for detecting and reporting a plurality of different target polynucleotide sequences in a sample, such as polynucleotides corresponding to a plurality of different genes expressed by a cell or cells. In particular, the invention provides methods for screening a plurality of candidate polynucleotide probes to evaluate both the sensitivity and the specificity with which each candidate probe hybridizes to a target polynucleoide sequence. Candidate polynucleotide probes can then be ranked according to both their sensitivity and specificity, and probes that have optimal sensitivity and specificity for a target polynucleotide sequence can be selected. In one embodiment, polynucleotide probes can be selected according to the methods described herein to prepare “screening chips” wherein a large number of target polynucleotide sequences are detected using a single microarray have a few (e.g., 1–5) probes for each target polynucleotide sequence. In a particularly preferred embodiment, the invention provides a screening chip that can detect genetic transcripts from the entire genome of an organism. In an alternative embodiment, polynucleotide probes can be selected according to the methods described herein to prepare “signature chips” to more accurately detect certain selected “signature genes” using several polynucleotide probes (e.g., 10–20) for each signature gene. The invention additionally provides microarrays containing polynucleotide probes for a large number of genes expressed by a cell or organism. Further, methods for detecting a plurality of polynucleotide molecules, including a large number of genes expressed by a cell or organism, are also provided.
摘要翻译：提供了可用于检测和报告样品中多个不同靶多核苷酸序列的方法和组合物，例如对应于由细胞或细胞表达的多种不同基因的多核苷酸。特别地，本发明提供了筛选多个候选多核苷酸探针以评估每个候选探针与目标多核苷酸序列杂交的灵敏度和特异性的方法。然后可以根据其灵敏度和特异性对候选多核苷酸探针进行排序，并且可以选择对靶多核苷酸序列具有最佳敏感性和特异性的探针。在一个实施方案中，可以根据本文所述的方法选择多核苷酸探针以制备“筛选芯片”，其中使用单个微阵列检测大量目标多核苷酸序列，其中每个靶多核苷酸具有少量（例如1-5）探针序列。在一个特别优选的实施方案中，本发明提供了可以检测来自生物体的整个基因组的遗传转录物的筛选芯片。在替代实施方案中，可以根据本文所述的方法选择多核苷酸探针以通过使用每个特征基因的多个多核苷酸探针（例如10-20）来制备“签名芯片”以更精确地检测某些所选择的“特征基因”。本发明另外提供含有由细胞或生物表达的大量基因的多核苷酸探针的微阵列。此外，还提供了用于检测多个多核苷酸分子的方法，包括由细胞或生物体表达的大量基因。

10. 发明申请

US20110250591A1 METHOD OF DESIGNING siRNAS FOR GENE SILENCING 有权
标题翻译：设计用于基因沉默的siRNA的方法
公开(公告)号：US20110250591A1
公开(公告)日：2011-10-13
申请号：US13100836
申请日：2011-05-04
申请人： Aimee L. Jackson , Steven R. Bartz , Julja Burchard , Peter S. Linsley , Wei Ge , Guy L. Cavet
发明人： Aimee L. Jackson , Steven R. Bartz , Julja Burchard , Peter S. Linsley , Wei Ge , Guy L. Cavet
IPC分类号： C12Q1/68
CPC分类号： C12N15/111 , C12N2310/14 , C12N2320/11 , C12N2330/31 , G06F19/18 , G06F19/22
摘要： The present invention provides a method for identifying siRNA target motifs in a transcript using a position-specific score matrix approach. The invention also provides a method for identifying off-target genes of an siRNA using a position-specific score matrix approach. The invention further provides a method for designing siRNAs with higher silencing efficacy and specificity. The invention also provides a library of siRNAs comprising siRNAs with high silencing efficacy and specificity.
摘要翻译：本发明提供使用位置特异性评分矩阵法来鉴定转录物中的siRNA靶基序的方法。本发明还提供了一种使用位置特异性评分矩阵方法鉴定siRNA的靶外基因的方法。本发明还提供了设计具有较高沉默功效和特异性的siRNA的方法。本发明还提供了包含具有高沉默功效和特异性的siRNA的siRNA文库。

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