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    Mammalian genes involved in rapamycin resistance and tumorgenesis annexin XIII genes
    14.
    发明申请
    Mammalian genes involved in rapamycin resistance and tumorgenesis annexin XIII genes 审中-公开
    哺乳动物基因涉及雷帕霉素抗性和肿瘤发生膜联蛋白XIII基因

    公开(公告)号：US20060052320A1

    公开(公告)日：2006-03-09

    申请号：US10513780

    申请日：2003-05-06

    申请人： Limin Li

    发明人： Limin Li

    IPC分类号： A61K48/00 ,  C12N15/87

    CPC分类号： A61K38/1709 ,  A01K2217/05 ,  A01K2217/075 ,  A01K2267/02 ,  A61K48/005 ,  C12N15/8509 ,  C12N2800/30 ,  C12N2830/006 ,  C12N2840/203 ,  C12N2840/44 ,  C12Q1/6886 ,  C12Q2600/136

    摘要： The present invention provides methods and compositions for regulating rapamycin resistance and/or tumorgenesis by modulating the expression and/or the activity of annexin XIII gene. The invention also provides methods and compositions for treatment of diseases, e.g., cancers, by modulating the expression and/or activity of annexin XIII gene. The invention also provides methods and compositions for diagnosing and screening annexin XIII mediated rapamycin resistance and/or tumorgenesis in patients. The invention further provides host cells whose annexin XIII gene can be reversibly switched on or off, and to methods of using annexin XIII gene in evaluation and screening for drugs which regulate rapamycin resistance and/or tumorgenesis. The invention also provides methods for generating genetically modified cells having altered sensitivity to rapamycin by knocking out a gene which mediates rapamycin resistance.

    摘要翻译： 本发明提供通过调节膜联蛋白XIII基因的表达和/或活性来调节雷帕霉素抗性和/或肿瘤发生的方法和组合物。 本发明还提供了通过调节膜联蛋白XIII基因的表达和/或活性来治疗疾病例如癌症的方法和组合物。 本发明还提供用于诊断和筛选患者中膜联蛋白XIII介导的雷帕霉素抗性和/或肿瘤发生的方法和组合物。 本发明还提供其膜联蛋白XIII基因可以可逆地开启或关闭的宿主细胞，以及使用膜联蛋白XIII基因评估和筛选调节雷帕霉素抗性和/或肿瘤发生的药物的方法。 本发明还提供了通过敲除介导雷帕霉素抗性的基因来产生对雷帕霉素敏感性改变的遗传修饰细胞的方法。

    Methods and combinations for gene targeting by homologous recombination
    15.
    发明申请
    Methods and combinations for gene targeting by homologous recombination 审中-公开
    通过同源重组进行基因靶向的方法和组合

    公开(公告)号：US20050118648A1

    公开(公告)日：2005-06-02

    申请号：US10490830

    申请日：2002-09-27

    申请人： Limin Li

    发明人： Limin Li

    IPC分类号： C12N15/90 ,  C12Q1/68 ,  C12N15/85 ,  G01N33/53 ,  G01N33/567

    CPC分类号： C12N15/902

    摘要： The invention provides methods and compositions for inserting a DNA sequence in the genome of a cell by homologous recombination. In particular, the method utilizes a selection scheme in which a selection marker gene that encodes a fluorescence protein, such as a green fluorescence protein, is used for selection against random, non homologous insertions.

    摘要翻译： 本发明提供了通过同源重组将DNA序列插入细胞基因组中的方法和组合物。 特别地，该方法利用选择方案，其中编码荧光蛋白的选择标记基因，如绿色荧光蛋白，用于针对随机，非同源插入的选择。

    Method for concurrent disruption of expression of multiple alleles of mammalian genes
    16.
    发明授权
    Method for concurrent disruption of expression of multiple alleles of mammalian genes 失效
    同时破坏哺乳动物基因多重等位基因表达的方法

    公开(公告)号：US5679523A

    公开(公告)日：1997-10-21

    申请号：US585758

    申请日：1996-01-16

    申请人： Limin Li ,  Stanley N. Cohen

    发明人： Limin Li ,  Stanley N. Cohen

    IPC分类号： C07K14/47 ,  C12N15/00 ,  C12Q1/68 ,  C07H21/04

    CPC分类号： C12Q1/68 ,  C07K14/4702 ,  C12N15/00

    摘要： Methods are provided for identifying a gene at a random chromosomal locus in the genome of a mammalian cell. The method involves inactivating one copy of the gene by integrating one DNA construct (knockout construct) in that gene copy. The knockout construct includes a positive selection marker region sequence and, in a 5' direction from the selection marker region sequence, a transcription initiation region sequence responsive to a transactivation factor, said transcription initiation region oriented for antisense RNA transcription in the direction away from the selection marker region sequence. The second copy of the gene is inactivated by transforming the cells with a second DNA construct (transactivation construct) containing a gene sequence for the transactivation factor which initiates antisense RNA transcription extending from the knockout construct into the chromosomal locus flanking the knockout construct at its 5' end. Inactivation of both gene copies may result in a change in cell phenotype distinguishable from the wild-type phenotype. Optionally, the wild-type phenotype can be regained by introducing a third construct that can inhibit antisense RNA transcription.

    摘要翻译： 提供了用于鉴定哺乳动物细胞基因组中随机染色体基因座上的基因的方法。 该方法包括通过在该基因拷贝中整合一个DNA构建体（敲除构建体）来使基因的一个拷贝失活。 敲除构建体包括阳性选择标记区序列，并且在从选择标记区序列的5'方向上，对反式激活因子有反应的转录起始区序列，所述转录起始区取向为远离 选择标记区序列。 通过用包含反式激活因子的基因序列的第二个DNA构建体（反式激活构建体）转化细胞来灭活该基因的第二个拷贝，其启动从敲除构建体延伸到其敲除构建体侧翼的染色体基因座的5' ' 结束。 两种基因拷贝的失活可导致与野生型表型区分开的细胞表型的变化。 任选地，可以通过引入可抑制反义RNA转录的第三构建体来恢复野生型表型。

    Mammalian tumor susceptibility genes and their uses
    17.
    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

    申请人： Stanley N. Cohen ,  Limin Li

    发明人： Stanley N. Cohen ,  Limin Li

    IPC分类号： C07K14/435

    CPC分类号： G01N33/57415 ,  C07K14/4702 ,  C12N15/00 ,  C12Q1/68 ,  C12Q1/6886 ,  C12Q2600/118 ,  C12Q2600/136

    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
    18.
    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

    申请人： Limin Li ,  Stanley N. Cohen

    发明人： Limin Li ,  Stanley N. Cohen

    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。