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。

公开(公告)号：US20120072124A1

公开(公告)日：2012-03-22

申请号：US13207282

申请日：2011-08-10

申请人： Jerald P. Radich ,  Hongyue Dai ,  Mao Mao ,  Janell M. Schelter ,  Peter S. Linsley

发明人： Jerald P. Radich ,  Hongyue Dai ,  Mao Mao ,  Janell M. Schelter ,  Peter S. Linsley

IPC分类号： G06F19/20 ,  G01N33/50

CPC分类号： C12Q1/6886 ,  C12Q2600/106 ,  C12Q2600/112 ,  C12Q2600/136 ,  C12Q2600/158 ,  Y02A90/26

摘要： The invention provides molecular markers that are associated with the progression of chronic myeloid leukemia (CML), and methods and computer systems for monitoring the progression of CML in a patient based on measurements of these molecular markers. The present invention also provides CML target genes, and methods and compositions for treating CML patients by modulating the expression or activity of these CML target genes and/or their encoded proteins. The invention also provides genes that are associated with resistance to imatinib mesylate (Gleevec™) treatment in CML patients, and methods and compositions for determining the responsiveness of a CML patient to imatinib mesylate treatment based on measurements of these genes and/or their encoded proteins. The invention also provides methods and compositions for enhancing the effect of Gleevec™ by modulating the expression or activity of these genes and/or their encoded proteins.

摘要翻译： 本发明提供了与慢性骨髓性白血病（CML）进展相关的分子标记，以及用于基于这些分子标记物的测量来监测患者中CML进展的方法和计算机系统。 本发明还提供CML靶基因，以及通过调节这些CML靶基因和/或其编码蛋白的表达或活性来治疗CML患者的方法和组合物。 本发明还提供了与CML患者中对伊马替尼甲磺酸盐（Gleevec TM）治疗有关的基因，以及基于这些基因和/或其编码蛋白质的测量来确定CML患者对甲磺酸伊马替尼治疗的反应性的方法和组合物 。 本发明还提供了通过调节这些基因和/或其编码的蛋白质的表达或活性来增强Gleevec TM的作用的方法和组合物。

公开(公告)号：US08014957B2

公开(公告)日：2011-09-06

申请号：US11640517

申请日：2006-12-14

申请人： Jerald P. Radich ,  Hongyue Dai ,  Mao Mao ,  Janell M. Schelter ,  Peter S. Linsley

发明人： Jerald P. Radich ,  Hongyue Dai ,  Mao Mao ,  Janell M. Schelter ,  Peter S. Linsley

IPC分类号： G01N33/48

CPC分类号： C12Q1/6886 ,  C12Q2600/106 ,  C12Q2600/112 ,  C12Q2600/136 ,  C12Q2600/158 ,  Y02A90/26

摘要： The invention provides molecular markers that are associated with the progression of chronic myeloid leukemia (CML), and methods and computer systems for monitoring the progression of CML in a patient based on measurements of these molecular markers. The present invention also provides CML target genes, and methods and compositions for treating CML patients by modulating the expression or activity of these CML target genes and/or their encoded proteins. The invention also provides genes that are associated with resistance to imatinib mesylate (Gleevec™) treatment in CML patients, and methods and compositions for determining the responsiveness of a CML patient to imatinib mesylate treatment based on measurements of these genes and/or their encoded proteins. The invention also provides methods and compositions for enhancing the effect of Gleevec™ by modulating the expression or activity of these genes and/or their encoded proteins.

摘要翻译： 本发明提供了与慢性骨髓性白血病（CML）进展相关的分子标记，以及用于基于这些分子标记物的测量来监测患者中CML进展的方法和计算机系统。 本发明还提供CML靶基因，以及通过调节这些CML靶基因和/或其编码蛋白的表达或活性来治疗CML患者的方法和组合物。 本发明还提供了与CML患者中对伊马替尼甲磺酸盐（Gleevec TM）治疗有关的基因，以及基于这些基因和/或其编码蛋白质的测量来确定CML患者对甲磺酸伊马替尼治疗的反应性的方法和组合物 。 本发明还提供了通过调节这些基因和/或其编码的蛋白质的表达或活性来增强Gleevec TM的作用的方法和组合物。

公开(公告)号：US06271002B1

公开(公告)日：2001-08-07

申请号：US09411074

申请日：1999-10-04

申请人： Peter S. Linsley ,  Janell M. Schelter

发明人： Peter S. Linsley ,  Janell M. Schelter

IPC分类号： C12P1934

CPC分类号： C12N15/1096

摘要： The present invention relates to methods and kits for amplification of mRNA using a primer in PCR that contains an RNA polymerase promoter. The invention provides methods for amplification and detection of RNA derived from a population of cells, preferably eukaryotic cells and most preferably mammalian cells, which methods preserve fidelity with respect to sequence and transcript representation, and additionally enable amplification of extremely small amounts of mRNA, such as might be obtained from 106 mammalian cells. In typical embodiments of the invention, an RNA polymerase promoter (RNAP) is incorporated into ds cDNA by priming cDNA amplification by polymerase chain reaction (PCR) with an RNAP-containing primer. Following less than 20 cycles of PCR, the resultant RNAP-containing ds cDNA is transcribed into RNA using an RNA polymerase capable of binding to the RNAP introduced during cDNA synthesis. This combination of PCR and in vitro transcription (IVT) enables the generation of a relatively large amount of RNA from a small starting number of cells without loss of fidelity. RNAs generated using this method may be labeled and employed to profile gene expression in different populations of cells, e.g., by use of a polynucleotide microarray.

摘要翻译： 本发明涉及使用含有RNA聚合酶启动子的PCR中的引物扩增mRNA的方法和试剂盒。 本发明提供了用于扩增和检测衍生自细胞群（优选真核细胞，最优选哺乳动物细胞）的RNA的方法，所述方法保持关于序列和转录物表达的保真度，并且还能够扩增极少量的mRNA，例如 可以从106个哺乳动物细胞获得。 在本发明的典型实施方案中，通过用含有RNAP的引物通过聚合酶链反应（PCR）引发cDNA扩增，将RNA聚合酶启动子（RNAP）引入ds cDNA。 在不到20个PCR循环后，使用能够结合cDNA合成引入的RNAP的RNA聚合酶将得到的含RNAP的ds cDNA转录成RNA。 PCR和体外转录（IVT）的这种组合使得能够从小的起始数量的细胞产生相对大量的RNA而不失去保真度。 使用该方法产生的RNA可以被标记并用于分析不同细胞群体中的基因表达，例如通过使用多核苷酸微阵列。