Selective Reduction of the Deleterious Activity of Extended Tri-Nucleotide Repeat Containing Genes
    3.
    发明申请
    Selective Reduction of the Deleterious Activity of Extended Tri-Nucleotide Repeat Containing Genes 有权
    选择性降低扩增的三核苷酸重复包含基因的有害活性

    公开(公告)号:US20130317088A1

    公开(公告)日:2013-11-28

    申请号:US13988605

    申请日:2011-12-08

    IPC分类号: A61K31/713

    摘要: Aspects of the invention include methods of selectively reducing the deleterious activity of mutant extended trinucleotide repeat containing genes in a cell, as well as compositions used in such methods. The deleterious activity (e.g., toxicity and/or dis-functionality of products encoded thereby) of a mutant extended trinucleotide repeat containing gene may be selectively reduced in a variety of different ways, e.g., by selectively decreasing SPT4 mediated transcriptional activity, by enhancing functionality of proteins encoded thereby, etc. Aspects of the invention further include assays for identifying agents that find use in methods of the invention, e.g. as summarized above. Methods and compositions of the invention find use in a variety of different applications, including the prevention or treatment of disease conditions associated with the presence of genes containing mutant extended trinucleotide repeats, such as Huntington's Disease (HD).

    摘要翻译: 本发明的方面包括选择性地降低细胞中突变型延伸三核苷酸重复含基因的有害活性的方法,以及用于这些方法的组合物。 突变型延伸三核苷酸重复含基因的有害活性(例如,由此编码的产物的毒性和/或功能异常)可以多种不同方式选择性地降低,例如通过增强功能性选择性降低SPT4介导的转录活性 由此编码的蛋白质等。本发明的方面还包括用于鉴定在本发明方法中使用的试剂的测定法,例如 如上所述。 本发明的方法和组合物可用于各种不同的应用,包括预防或治疗与含有突变型延伸三核苷酸重复序列(例如亨廷顿氏病(HD))的基因的存在相关的疾病状况。

    Selective reduction of the deleterious activity of extended tri-nucleotide repeat containing genes
    4.
    发明授权
    Selective reduction of the deleterious activity of extended tri-nucleotide repeat containing genes 有权
    延长三核苷酸重复基因的有害活性的选择性降低

    公开(公告)号:US09211303B2

    公开(公告)日:2015-12-15

    申请号:US13988605

    申请日:2011-12-08

    摘要: Aspects of the invention include methods of selectively reducing the deleterious activity of mutant extended trinucleotide repeat containing genes in a cell, as well as compositions used in such methods. The deleterious activity (e.g., toxicity and/or dis-functionality of products encoded thereby) of a mutant extended trinucleotide repeat containing gene may be selectively reduced in a variety of different ways, e.g., by selectively decreasing SPT4 mediated transcriptional activity, by enhancing functionality of proteins encoded thereby, etc. Aspects of the invention further include assays for identifying agents that find use in methods of the invention, e.g. as summarized above. Methods and compositions of the invention find use in a variety of different applications, including the prevention or treatment of disease conditions associated with the presence of genes containing mutant extended trinucleotide repeats, such as Huntington's Disease (HD).

    摘要翻译: 本发明的方面包括选择性地降低细胞中突变型延伸三核苷酸重复含基因的有害活性的方法,以及用于这些方法的组合物。 突变型延伸三核苷酸重复含基因的有害活性(例如,由此编码的产物的毒性和/或功能异常)可以多种不同方式选择性地降低,例如通过增强功能性选择性降低SPT4介导的转录活性 由此编码的蛋白质等。本发明的方面还包括用于鉴定在本发明方法中使用的试剂的测定法,例如 如上所述。 本发明的方法和组合物可用于各种不同的应用,包括预防或治疗与含有突变型延伸三核苷酸重复序列(例如亨廷顿氏病(HD))的基因的存在相关的疾病状况。

    Mammalian tumor susceptibility genes and their uses

    公开(公告)号:US08404807B2

    公开(公告)日:2013-03-26

    申请号:US13116911

    申请日:2011-05-26

    IPC分类号: C07K16/00 C07K14/00

    摘要: TSG101 is a tumor susceptibility gene whose homozygous functional knock out in fibroblasts leads to transformation and the ability of these cells to form metastatic tumors in nude mice. The cellular transformation that results from inactivation of TSG101 is reversible by restoration of TSG101 function. Decreased expression of TSG101 is associated with the occurrence of certain human cancers, including breast carcinomas. The TSG101 nucleic acid compositions find use in identifying homologous or related proteins and the DNA sequences encoding such proteins; in producing compositions that modulate the expression or function of the protein; and in studying associated physiological pathways. In addition, modulation of the gene activity in vivo is used for prophylactic and therapeutic purposes, such as treatment of cancer, identification of cell type based on expression, and the like. The DNA is further used as a diagnostic for a genetic predisposition to cancer, and to identify specific cancers having mutations in this gene.

    Method for synthesizing DNA sequentially
    6.
    发明授权
    Method for synthesizing DNA sequentially 失效
    顺序合成DNA的方法

    公开(公告)号:US4293652A

    公开(公告)日:1981-10-06

    申请号:US042403

    申请日:1979-05-25

    申请人: Stanley N. Cohen

    发明人: Stanley N. Cohen

    IPC分类号: C12N15/10 C12N15/00

    CPC分类号: C12N15/10 Y10S435/82

    摘要: A method and a DNA linker are described for synthesizing relatively long double-stranded deoxyribonucleic acid sequences of defined composition. Short complementary single strand segments of oligonucleotides comprising part of the full sequence desired are synthesized using known procedures. Overlapping single strand segments are annealed forming double-stranded fragments which are inserted in cloning vectors and cloned in an appropriate host, both purifying the DNA fragments and amplifying the amount thereof. An adjacent fragment is then similarly synthesized in quantity and such fragments are inserted adjacent to the first synthetic introduced fragments in the cloning vectors, followed by cloning in an appropriate host. The procedure continues until the entire desired sequence has been formed, at which time it may be excised or cloned directly in the vectors upon which it was made. The described DNA linker contains a restriction enzyme recognition sequence for a restriction enzyme which cuts offset from the recognition sequence and exactly at the end of the linker, enabling synthesized DNA to be inserted at the end of the linker without disturbing the recognition sequence.

    摘要翻译: 描述了用于合成具有确定组成的相对较长的双链脱氧核糖核酸序列的方法和DNA连接体。 包含部分所需全序列的寡核苷酸短链互补链段是使用已知方法合成的。 重叠单链链段是退火形成双链片段,其插入克隆载体中并克隆在合适的宿主中,纯化DNA片段并扩增其量。 然后类似地合成相邻的片段,并将这些片段与克隆载体中的第一合成引入片段相邻插入,然后在合适的宿主中克隆。 该过程继续,直到形成完整的所需序列,此时可将其直接切割或克隆到其制备的载体中。 所描述的DNA连接体包含限制酶的限制酶识别序列,其限制酶从识别序列偏移并且恰好在接头的末端,使合成的DNA插入到接头的末端而不干扰识别序列。

    Mammalian tumor susceptibility genes and their uses
    8.
    发明授权
    Mammalian tumor susceptibility genes and their uses 失效
    哺乳动物肿瘤易感基因及其用途

    公开(公告)号:US07973130B2

    公开(公告)日:2011-07-05

    申请号:US10697720

    申请日:2003-10-29

    IPC分类号: C07K14/435

    摘要: TSG101 is a tumor susceptibility gene whose homozygous functional knock out in fibroblasts leads to transformation and the ability of these cells to form metastatic tumors in nude mice. The cellular transformation that results from inactivation of TSG101 is reversible by restoration of TSG101 function. Decreased expression of TSG101 is associated with the occurrence of certain human cancers, including breast carcinomas. The TSG101 nucleic acid compositions find use in identifying homologous or related proteins and the DNA sequences encoding such proteins; in producing compositions that modulate the expression or function of the protein; and in studying associated physiological pathways. In addition, modulation of the gene activity in vivo is used for prophylactic and therapeutic purposes, such as treatment of cancer, identification of cell type based on expression, and the like. The DNA is further used as a diagnostic for a genetic predisposition to cancer, and to identify specific cancers having mutations in this gene.

    摘要翻译: TSG101是一种肿瘤易感基因,其纯合功能敲除成纤维细胞导致转化和这些细胞在裸鼠中形成转移性肿瘤的能力。 由TSG101失活引起的细胞转化可通过恢复TSG101功能而逆转。 TSG101的表达降低与某些人类癌症(包括乳腺癌)的发生有关。 TSG101核酸组合物用于鉴定同源或相关蛋白质和编码此类蛋白质的DNA序列; 在制备调节蛋白质的表达或功能的组合物中; 并研究相关的生理学途径。 此外,体内基因活性的调节用于预防和治疗目的,例如癌症的治疗,基于表达的细胞类型的鉴别等。 该DNA进一步用于诊断癌症的遗传易感性,并鉴定具有该基因突变的特异性癌症。

    Mammalian tumor susceptibility gene products and their uses
    9.
    发明授权
    Mammalian tumor susceptibility gene products and their uses 失效
    哺乳动物肿瘤易感基因产物及其用途

    公开(公告)号:US07714108B2

    公开(公告)日:2010-05-11

    申请号:US10053975

    申请日:2002-01-18

    IPC分类号: C07K16/00 A61K39/395

    CPC分类号: C07K14/47 C07K16/18

    摘要: The present invention provides methods and compositions for regulating ubiquitination in a cell. In particular, the present invention provides purified polypeptides comprising an ubiquitination-regulating domain. The invention also provides methods of using such polypeptides for screening for agents, for producing antibodies, and for treatment of diseases, e.g., proliferative diseases, neurodegenerative diseases, autoimmune diseases, metabolic disease and developmental abnormalities. The invention further provides antibodies that bind an ubiquitination-regulating domain and agents and antibodies that regulate ubiquitination in cells, e.g., by modulating the interaction between a TSG101 protein and an MDM2 protein.

    摘要翻译: 本发明提供用于调节细胞中泛素化的方法和组合物。 特别地,本发明提供了包含泛素调节结构域的纯化多肽。 本发明还提供了使用这种多肽筛选试剂,产生抗体和治疗疾病如增殖性疾病,神经变性疾病,自身免疫性疾病,代谢疾病和发育异常的方法。 本发明还提供结合泛素调节结构域的抗体以及调节细胞中的泛素化的试剂和抗体,例如通过调节TSG101蛋白和MDM2蛋白之间的相互作用。