公开(公告)号：US5780220A

公开(公告)日：1998-07-14

申请号：US382873

申请日：1995-02-03

申请人： David B. Weiner ,  Yosef Refaeli ,  David N. Levy

发明人： David B. Weiner ,  Yosef Refaeli ,  David N. Levy

IPC分类号： A61K38/00 ,  C07K14/16 ,  C07K16/10 ,  C12P21/08 ,  G01N33/569 ,  C12Q1/70 ,  A01N43/04 ,  A61K31/56 ,  G01N33/53

CPC分类号： C07K14/005 ,  C07K16/1072 ,  G01N33/56988 ,  A61K38/00 ,  C12N2740/16322 ,  Y10S514/01

摘要： A method for treating an individual exposed to or infected with HIV is disclosed which comprises administering to said individual a therapeutically effective amount of one or more compounds which inhibit or prevent replication of said HIV by interfering with the replicative or other essential functions of Vpr expressed by said HIV, by interactively blocking the Vpr target in human cells, and thereby preventing translocation of the Vpr/target complex from the cytosol of said human cells to the nuclei of said cells, where Vpr carries on activities essential to replication of HIV. In preferred embodiments, the compound or compounds which interactively block the target are steroid hormone receptor antagonists, glucocorticoid receptor antagonists, or glucocorticoid receptor Type II antagonists, especially mifepristone (RU-486). Pharmaceutical compositions comprising these compounds, as well as a method for identifying them and a kit for use therein, are also disclosed.

摘要翻译： 公开了一种用于治疗暴露于或感染HIV的个体的方法，其包括向所述个体施用治疗有效量的一种或多种化合物，所述一种或多种化合物通过干扰由Vpr表达的Vpr的复制或其它基本功能来抑制或阻止所述HIV的复制 所述HIV通过交互阻断人细胞中的Vpr靶，从而防止Vpr /靶复合物从所述人细胞的胞质溶胶转移到所述细胞的细胞核，其中Vpr进行HIV复制必需的活性。 在优选的实施方案中，交互地阻断靶标的化合物或类似物是类固醇激素受体拮抗剂，糖皮质激素受体拮抗剂或糖皮质激素受体II型拮抗剂，特别是米非司酮（RU-486）。 还公开了包含这些化合物的药物组合物，以及用于鉴定它们的方法和用于其中的试剂盒。

公开(公告)号：US5639598A

公开(公告)日：1997-06-17

申请号：US246177

申请日：1994-05-19

申请人： David B. Weiner ,  Yosef Refaeli ,  David N. Levy

发明人： David B. Weiner ,  Yosef Refaeli ,  David N. Levy

IPC分类号： A61K38/00 ,  C07K14/16 ,  C07K16/10 ,  G01N33/569 ,  C12Q1/70 ,  G01N33/53

CPC分类号： C07K14/005 ,  C07K16/1072 ,  G01N33/56988 ,  A61K38/00 ,  C12N2740/16322 ,  Y10S514/01

摘要： Human and simian immunodeficiency viruses (HIV/SIVs) contain, in addition to the canonical gag/pol/env genes, additional small open reading frames (ORFs) encoding gene products, including the 96-amino acid 15-kDa virion-associated HIV-1 Vpr gene product. Vpr functions as a regulator of cellular processes related to HIV replication. A biologically active recombinant HIV-1 Vpr protein was employed as a ligand to identify its cognate cellular target(s). A novel 41-kDa cytosolic viral protein R interacting protein, designated Rip-1, was identified using the recited assay. Rip-1 displays a wide-tissue distribution, including relevant targets of HIV infection. HIV-1 Vpr induced nuclear translocation of Rip-1. This invention provides novel biochemical reagents and methods that will facilitate the identification of antiviral agents.

摘要翻译： 除了典型的gag / pol / env基因之外，人和猿免疫缺陷病毒（HIV / SIV）还包含编码基因产物的其他小型开放阅读框（ORF），包括96-氨基酸15-kDa病毒体相关的HIV- 1 Vpr基因产物。 Vpr作为与HIV复制有关的细胞过程的调节剂。 使用生物活性的重组HIV-1 Vpr蛋白作为配体来鉴定其同源细胞靶标。 使用所述测定法鉴定了一种名为Rip-1的新型41-kDa胞质病毒蛋白R相互作用蛋白。 Rip-1显示广泛的组织分布，包括艾滋病毒感染的相关目标。 HIV-1Vpr诱导Rip-1的核易位。 本发明提供了促进抗病毒剂鉴定的新型生物化学试剂和方法。

公开(公告)号：US06667157B1

公开(公告)日：2003-12-23

申请号：US08809186

申请日：1997-06-24

申请人： David B. Weiner ,  David N. Levy ,  Yosef Refaeli ,  William V. Williams ,  Velpandi Ayyavoo

发明人： David B. Weiner ,  David N. Levy ,  Yosef Refaeli ,  William V. Williams ,  Velpandi Ayyavoo

IPC分类号： G01N33567

CPC分类号： C07K14/005 ,  A61K38/162 ,  A61K48/00 ,  C12N2710/14143 ,  C12N2740/16322

摘要： Method of inhibiting proliferation of cells using vpr protein or nucleotide sequences that encode vpr are disclosed. Method of preventing lymphocyte activation using vpr protein or nucleotide sequences that encode vpr are disclosed. Methods of treating an individual diagnosed with or suspected of suffering from autoimmune disease, diseases characterized by proliferating cells and graft versus host disease by administering vpr protein or a functional fragment thereof, or a nucleic acid molecule that comprises a nucleotide sequence that encodes vpr protein or a functional fragment thereof are disclosed. Conjugated compositions for delivery of active agents to the nucleus of cells are disclosed.

摘要翻译： 公开了使用vpr蛋白抑制细胞增殖的方法或编码vpr的核苷酸序列。 公开了使用vpr蛋白或编码vpr的核苷酸序列预防淋巴细胞活化的方法。 治疗患有或怀疑患有自身免疫疾病的个体的方法，通过施用vpr蛋白或其功能片段或包含编码vpr蛋白的核苷酸序列的核酸分子的核酸分子，或者包含编码vpr蛋白的核苷酸序列的核酸分子， 公开了其功能片段。 公开了将活性剂递送至细胞核的共轭组合物。

公开(公告)号：US5714316A

公开(公告)日：1998-02-03

申请号：US147890

申请日：1993-11-04

申请人： David Weiner ,  William Williams ,  David N. Levy

发明人： David Weiner ,  William Williams ,  David N. Levy

IPC分类号： A61K38/00 ,  A61K47/48 ,  C07K14/16 ,  C07K14/535 ,  C07K14/73 ,  C12N7/01 ,  C12N15/867 ,  C12Q1/68 ,  C07H21/02 ,  C12N15/00 ,  C12Q1/70

CPC分类号： C12N15/86 ,  A61K47/48776 ,  C07K14/005 ,  C07K14/535 ,  C07K14/70514 ,  A61K38/00 ,  C07K2319/00 ,  C12N2740/16043 ,  C12N2740/16045 ,  C12N2740/16222 ,  C12N2810/50 ,  C12N2810/852 ,  C12N2810/855

摘要： The present invention provides compositions and methods for targeting recombinant retroviral particles specifically to cells of interest for delivery of desired therapeutic or toxic agents. The invention provides chimeric nucleotide constructs, chimeric proteins formed of a selected viral envelope gene from which a selected sequence has been deleted and into which has been inserted all or an effective portion of a heterologous ligand, said ligand or portion thereof capable of binding to a selected receptor, recombinant viral particles formed of the chimeric proteins, a biological mediator for delivery to the target cell; and retroviral gag and pol proteins. The lack of retroviral nucleic acid renders the viral particle replication defective and non-pathogenic.

摘要翻译： 本发明提供用于特异性靶向重组逆转录病毒颗粒的组合物和方法，用于递送所需治疗剂或毒性剂。 本发明提供嵌合核苷酸构建体，由所选择的病毒包膜基因形成的嵌合蛋白，所选择的序列已经被缺失，并且已经插入了全部或有效部分的异源配体，所述配体或其部分能够结合到 选择的受体，由嵌合蛋白形成的重组病毒颗粒，用于递送至靶细胞的生物介体; 和逆转录病毒gag和pol蛋白。 逆转录病毒核酸的缺乏使得病毒颗粒复制有缺陷和非致病性。

公开(公告)号：US20080118494A1

公开(公告)日：2008-05-22

申请号：US11661881

申请日：2005-09-02

申请人： Olaf Kutsch ,  Jennifer Jones ,  George M. Shaw ,  David N. Levy

发明人： Olaf Kutsch ,  Jennifer Jones ,  George M. Shaw ,  David N. Levy

IPC分类号： A61K35/76 ,  C12N7/00 ,  C12N5/06 ,  C12Q1/70 ,  A61P43/00 ,  A61K39/00 ,  A61K39/395

CPC分类号： C12Q1/6897 ,  C12Q1/18 ,  G01N2333/16

摘要： Provided herein are compositions and methods that allow for the study of HIV latency and reactivation. Further provided are compositions and methods for in vitro screening of agents for their ability to reactivate, suppress reactivation or inhibit transcription of HIV. Compositions for and methods for activating a cell are also provided herein. Further provided herein are methods of treating a subject using agents that reactivate latent HIV infection or agents that inhibit HIV transcription. Also provided herein are methods of activating a latent microbiological entity in a subject. Further provided herein are methods for enhancing an immune response in a subject and compositions used as a vaccination adjuvant. Methods of making disclosed cells and compositions are also provided herein.

摘要翻译： 本文提供了允许研究HIV潜伏期和再激活的组合物和方法。 进一步提供的是用于体外筛选试剂以恢复，抑制再激活或抑制HIV转录的能力的组合物和方法。 本文还提供了用于激活细胞的组合物和方法。 本文还提供了使用重新激活潜伏HIV感染的药剂或抑制HIV转录的药物治疗受试者的方法。 本文还提供了激活受试者中的潜在微生物实体的方法。 本文还提供了用于增强受试者的免疫应答的方法和用作接种佐剂的组合物。 本文还提供制备公开的细胞和组合物的方法。