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49 条记录 (耗时 0.048 秒)

    Expression monitoring by hybridization to high density nucleic acid arrays
    32.
    发明授权
    Expression monitoring by hybridization to high density nucleic acid arrays 有权
    通过与高密度核酸阵列杂交进行表达监测

    公开(公告)号：US06410229B1

    公开(公告)日：2002-06-25

    申请号：US09212004

    申请日：1998-12-14

    申请人： David J. Lockhart ,  Eugene L. Brown ,  Gordon G. Wong ,  Mark S. Chee ,  Thomas R. Gingeras

    发明人： David J. Lockhart ,  Eugene L. Brown ,  Gordon G. Wong ,  Mark S. Chee ,  Thomas R. Gingeras

    IPC分类号： C12Q168

    CPC分类号： C12Q1/6809 ,  C12Q1/6837 ,  G01N15/1475 ,  C12Q2565/507

    摘要： This invention provides methods of monitoring the expression levels of a multiplicity of genes. The methods involve hybridizing a nucleic acid sample to a high density array of oligonucleotide probes where the high density array contains oligonucleotide probes complementary to subsequences of target nucleic acids in the nucleic acid sample. In one embodiment, the method involves providing a pool of target nucleic acids comprising RNA transcripts of one or more target genes, or nucleic acids derived from the RNA transcripts, hybridizing said pool of nucleic acids to an array of oligonucleotide probes immobilized on surface, where the array comprising more than 100 different oligonucleotides and each different oligonucleotide is localized in a predetermined region of the surface, the density of the different oligonucleotides is greater than about 60 different oligonucleotides per 1 cm2, and the olignucleotide probes are complementary to the RNA transcripts or nucleic acids derived from the RNA transcripts; and quantifying the hybridized nucleic acids in the array.

    摘要翻译： 本发明提供监测多种基因的表达水平的方法。 所述方法包括将核酸样品与寡核苷酸探针的高密度阵列杂交，其中高密度阵列含有与核酸样品中靶核酸的子序列互补的寡核苷酸探针。 在一个实施方案中，所述方法包括提供包含一个或多个靶基因的RNA转录物或衍生自RNA转录物的核酸的靶核酸库，将所述核酸库与固定在表面上的寡核苷酸探针阵列杂交，其中 包含超过100种不同寡核苷酸的阵列和每种不同的寡核苷酸被定位在表面的预定区域中，不同寡核苷酸的密度大于每1cm 2大约60个不同的寡核苷酸，并且寡核苷酸探针与RNA转录物互补 衍生自RNA转录物的核酸; 并定量阵列中的杂交核酸。

    METHODS OF ENZYMATIC DISCRIMINATION ENHANCEMENT AND SURFACE-BOUND DOUBLE-STRANDED DNA
    36.
    发明申请
    METHODS OF ENZYMATIC DISCRIMINATION ENHANCEMENT AND SURFACE-BOUND DOUBLE-STRANDED DNA 有权
    酶切鉴定增强和表面双重双链DNA的方法

    公开(公告)号：US20100216656A1

    公开(公告)日：2010-08-26

    申请号：US12187503

    申请日：2008-08-07

    申请人： David J. Lockhart ,  Mark S. Chee ,  Dirk Vetter ,  Martin Digglemann

    发明人： David J. Lockhart ,  Mark S. Chee ,  Dirk Vetter ,  Martin Digglemann

    IPC分类号： C40B30/04 ,  C40B60/12

    CPC分类号： C40B60/12 ,  B01J2219/00427 ,  B01J2219/00529 ,  B01J2219/00596 ,  B01J2219/00608 ,  B01J2219/00659 ,  B01J2219/00722 ,  C12Q1/6837 ,  C12Q1/6869 ,  C12Q2565/507 ,  C12Q2521/501

    摘要： Methods for discriminating between fully complementary hybrids and those that differ by one or more base pairs and libraries of unimolecular, double-stranded oligonucleotides on a solid support. In one embodiment, the present invention provides methods of using nuclease treatment to improve the quality of hybridization signals on high density oligonucleotide arrays. In another embodiment, the present invention provides methods of using ligation reactions to improve the quality of hybridization signals on high density oligonucleotide arrays. In yet another embodiment, the present invention provides libraries of unimolecular or intermolecular, double-stranded oligonucleotides on a solid support. These libraries are useful in pharmaceutical discovery for the screening of numerous biological samples for specific interactions between the double-stranded oligonucleotides, and peptides, proteins, drugs and RNA. In a related aspect, the present invention provides libraries of conformationally restricted probes on a solid support. The probes are restricted in their movement and flexibility using double-stranded oligonucleotides as scaffolding. The probes are also useful in various screening procedures associated with drug discovery and diagnosis. The present invention further provides methods for the preparation and screening of the above libraries.

    摘要翻译： 用于区分完全互补的杂交体与通过一个或多个碱基对不同的那些的方法和在固体支持物上的单分子双链寡核苷酸的文库。 在一个实施方案中，本发明提供了使用核酸酶处理来提高高密度寡核苷酸阵列上杂交信号质量的方法。 在另一个实施方案中，本发明提供了使用连接反应来提高高密度寡核苷酸阵列上杂交信号质量的方法。 在另一个实施方案中，本发明提供了在固体支持物上的单分子或分子间双链寡核苷酸的文库。 这些文库在药物发现中可用于筛选许多生物样品，用于双链寡核苷酸与肽，蛋白质，药物和RNA之间的特异性相互作用。 在相关方面，本发明提供了在固体支持物上的构象限制探针的文库。 使用双链寡核苷酸作为脚手架，探针的运动和灵活性受到限制。 探针也可用于与药物发现和诊断相关的各种筛选程序。 本发明还提供了制备和筛选上述文库的方法。

    Uncoupling of DNA insert propagation and expression of protein for phage display
    37.
    发明申请
    Uncoupling of DNA insert propagation and expression of protein for phage display 有权
    DNA插入片段的解偶联和蛋白质的表达用于噬菌体展示

    公开(公告)号：US20080318298A1

    公开(公告)日：2008-12-25

    申请号：US11982392

    申请日：2007-10-31

    申请人： Pietro Ciceri ,  Patrick Parvis Zarrinkar ,  Daniel Kelly Treiber ,  David J. Lockhart

    发明人： Pietro Ciceri ,  Patrick Parvis Zarrinkar ,  Daniel Kelly Treiber ,  David J. Lockhart

    IPC分类号： C12N7/01 ,  C12N15/63

    CPC分类号： C07H21/04 ,  C12N15/1037 ,  C40B40/02

    摘要： The present invention provides an advance in phage display technology by permitting the uncoupling of the propagation of phages containing inserted sequences encoding heterologous polypeptides from the expression of said polypeptides. The invention provides phage constructs and methods for their use to permit phage coat protein expression, and thus phage propagation, in the absence of display of heterologous polypeptides, which may be expressed as a fusion with said coat protein in a regulated manner.

    摘要翻译： 本发明通过允许从所述多肽的表达中分离含有编码异源多肽的插入序列的噬菌体的繁殖来提供噬菌体展示技术的进步。 本发明提供了噬菌体构建体和方法，用于在不显示异源多肽的情况下允许噬菌体外壳蛋白表达，从而允许噬菌体扩增，从而可以以调节的方式表达为与所述外壳蛋白的融合。