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    Zinc finger protein derivatives and methods therefor
    1.
    发明授权
    Zinc finger protein derivatives and methods therefor 失效
    锌指蛋白衍生物及其方法

    公开(公告)号：US06790941B2

    公开(公告)日：2004-09-14

    申请号：US09500700

    申请日：2000-02-09

    申请人： Carlos F. Barbas, III ,  Joel M. Gottesfeld ,  Peter E. Wright

    发明人： Carlos F. Barbas, III ,  Joel M. Gottesfeld ,  Peter E. Wright

    IPC分类号： C07K100

    CPC分类号： C07K14/46 ,  A61K38/00 ,  A61K48/00 ,  C07K14/4702 ,  C07K2319/00 ,  C07K2319/02 ,  C07K2319/09 ,  C07K2319/24 ,  C07K2319/42 ,  C07K2319/71 ,  C07K2319/73 ,  C07K2319/735 ,  C07K2319/81 ,  C12N15/62 ,  C12Q1/68 ,  G01N33/5008 ,  G01N33/5011 ,  G01N33/502 ,  G01N33/56988 ,  G01N33/68

    摘要： Zinc finger proteins of the Cys2His2 type represent a class of malleable DNA binding proteins which may be selected to bind diverse sequences. Typically, zinc finger proteins containing three zinc finger domains, like the murine transcription factor Zif268 and the human transcription factor Sp1, bind nine contiguous base pairs (bp). To create a class of proteins which would be generally applicable to target unique sites within complex genomes, the present invention provides a polypeptide linker that fuses two three-finger proteins. Two six-fingered proteins were created and demonstrated to bind 18 contiguous bp of DNA in a sequence specific fashion. Expression of these proteins as fusions to activation or repression domains allows transcription to be specifically up or down modulated within cells. Polydactyl zinc finger proteins are broadly applicable as genome-specific transcriptional switches in gene therapy strategies and the development of novel transgenic plants and animals. Such proteins are useful for inhibiting, activating or enhancing gene expression from a zinc finger-nucleotide binding motif containing promoter or other transcriptional control element, as well as a structural gene or RNA sequence.

    摘要翻译： Cys2His2型的锌指蛋白表示可以选择以结合不同序列的一类可延展的DNA结合蛋白。 通常，含有三个锌指结构域的锌指蛋白，如鼠转录因子Zif2​​68和人转录因子Sp1，结合九个连续的碱基对（bp）。 为了产生通常适用于在复杂基因组内靶向独特位点的一类蛋白质，本发明提供融合两个三指蛋白的多肽接头。 产生两个六指蛋白质并证明以序列特异性方式结合18个连续的DNA DNA。 这些蛋白质作为融合物的活化或抑制结构域的表达允许转录在细胞内特异性上调或下调。 多糖基锌指蛋白广泛适用于基因治疗策略中的基因组特异性转录转换和新型转基因植物和动物的开发。 这样的蛋白质可用于从含有锌指核苷酸结合基序的启动子或其他转录控制元件以及结构基因或RNA序列抑制，激活或增强基因表达。

    Complex formation between dsDNA and oligomer of cyclic heterocycles
    4.
    发明授权
    Complex formation between dsDNA and oligomer of cyclic heterocycles 有权
    双链DNA和环状杂环的低聚物之间的复合物形成

    公开(公告)号：US06303312B1

    公开(公告)日：2001-10-16

    申请号：US09434290

    申请日：1999-11-05

    申请人： Peter B. Dervan ,  Joel M. Gottesfeld

    发明人： Peter B. Dervan ,  Joel M. Gottesfeld

    IPC分类号： C12Q168

    CPC分类号： C12N15/63 ,  A61K38/00 ,  A61K47/645 ,  C07D207/34 ,  C07D233/90 ,  C07D403/14 ,  C07K7/02

    摘要： Methods and compositions are provided for forming complexes intracellularly between dsDNA and oligomers of heterocycles, aliphatic amino acids, particularly omega-amino acids, and a polar end group. By appropriate choice of target sequences and composition of the oligomers, complexes are obtained with low dissociation constants. The formation of complexes can be used for modifying the phenotype of cells, either prokaryotic or eukaryotic, for research and therapy.

    摘要翻译： 提供了用于在dsDNA和杂环，脂族氨基酸，特别是ω-氨基酸的低聚物和极性端基之间在细胞内形成复合物的方法和组合物。 通过适当选择靶序列和低聚物的组成，可以获得具有低解离常数的复合物。 复合物的形成可用于改变原核或真核细胞的表型，用于研究和治疗。

    Inhibition of gene transcription by polyamide DNA-binding ligands
    5.
    发明授权
    Inhibition of gene transcription by polyamide DNA-binding ligands 有权
    通过聚酰胺DNA结合配体抑制基因转录

    公开(公告)号：US06660255B1

    公开(公告)日：2003-12-09

    申请号：US09367513

    申请日：2000-04-25

    申请人： Joel M. Gottesfeld ,  Peter B. Dervan ,  Donald E. Mosier ,  Eldon E. Baird

    发明人： Joel M. Gottesfeld ,  Peter B. Dervan ,  Donald E. Mosier ,  Eldon E. Baird

    IPC分类号： A61K31785

    CPC分类号： A61K47/645 ,  A61K47/595

    摘要： The invention provides polyamides suitable for modulating cellular or viral gene expression by binding to an identified target DNA sequence adjacent to the binding site of a minor groove transcription factor protein. The polyamides of the present invention are useful for the treatment of a human infected with a virus such as HIV-1. The polyamides of the present invention are also useful for the treatment of conditions, such as cancers, that result from the expression or over-expression of cellular genes, particularly oncogenes.

    摘要翻译： 本发明提供了适合于通过与邻近小槽转录因子蛋白的结合位点的鉴定的靶DNA序列结合来调节细胞或病毒基因表达的聚酰胺。 本发明的聚酰胺可用于治疗感染病毒如HIV-1的人。 本发明的聚酰胺也可用于治疗由细胞基因，特别是致癌基因的表达或过表达导致的病症如癌症。