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1. 发明申请

WO2002098457A2 RECOMBINANT RHABDOVIRUSES AS LIVE-VIRAL VACCINES FOR IMMUNODEFICIENCY VIRUSES 审中-公开
标题翻译：作为免疫缺陷病毒的真菌病毒的重组病毒血红蛋白
公开(公告)号：WO2002098457A2
公开(公告)日：2002-12-12
申请号：PCT/US2002/000295
申请日：2002-01-08
申请人： THOMAS JEFFERSON UNIVERSITY , POMERANTZ, Roger, J. , SCHNELL, Matthias, J.
发明人： POMERANTZ, Roger, J. , SCHNELL, Matthias, J.
IPC分类号： A61K39/12
CPC分类号： C12N15/86 , A61K2039/525 , C07K14/005 , C12N2740/16122 , C12N2760/20022 , C12N2760/20043 , C12N2760/20045 , C12N2810/6081
摘要： This invention provides recombinant, replication-competent Rhabdovirus vaccine strain-based expression vectors for expressing heterologous viral antigenic polypeptides such as immunodeficiency virus envelope proteins or subparts thereof. An additional transcription stop/start unit within the Rhabdovirus genome is inserted to express the heterologouos antigenic polypeptides. The HIV-1 gp 160 protein is stably and functionally expressed, as indicated by fusion of human T cell-lines after infection with the recombinant RVs. Inoculation of mice with the recombinant Rabies viruses expressing HIV-1 gp160 induces a strong humoral response directed against the HIV-1 envelope protein after a single boost with an isolated recombinant HIV-1 gp120 protein. Moreover, high neutralization titers, Up to 1:800, against HIV-1 are detected in the mouse sera. The present invention also shows that a single vaccination with recombinant RV expressing HIV-1 envelope protein elicits a strong, long-lasting CTL response specific against HIV-1 proteins, such as the envelope protein of different HIV-1 strains. These recombinant viral vectors expressing viral antigenic polypeptides provide useful and effective pharmaceutical compositions for the generation of viral specific immune responses.
摘要翻译：本发明提供用于表达异源病毒抗原性多肽（例如免疫缺陷病毒包膜蛋白或其子部分）的重组，基于复制能力的基于弹状病毒基因毒株的表达载体。插入Rhabdovirus基因组内的另外的转录停止/起始单位以表达异源抗原多肽。 HIV-1 gp 160蛋白质是稳定和功能表达的，如通过重组RV感染后的人T细胞系的融合所表明的。用重组的表达HIV-1 gp160的狂犬病病毒接种小鼠，用分离的重组HIV-1 gp120蛋白单次加强后，诱导针对HIV-1包膜蛋白的强烈体液应答。此外，在小鼠血清中检测到针对HIV-1的高中和滴度，高达1：800。本发明还显示用重组RV表达HIV-1包膜蛋白的单次疫苗接种引起针对HIV-1蛋白（例如不同HIV-1毒株的包膜蛋白）特异性的强烈的持久的CTL反应。表达病毒抗原多肽的这些重组病毒载体提供用于产生病毒特异性免疫应答的有用和有效的药物组合物。

2. 发明申请

WO2003016539A1 RETROVIRAL VECTORS FOR GENE TRANSFER INTO NEURONAL CELLS 审中-公开
标题翻译：用于基因转移到神经细胞的转染载体
公开(公告)号：WO2003016539A1
公开(公告)日：2003-02-27
申请号：PCT/US2002/007547
申请日：2002-03-13
申请人： THOMAS JEFFERSON UNIVERSITY
发明人： DORNBURG, Ralph, C. , SCHNELL, Matthias, J. , DIETZSCHOLD, Bernhard
IPC分类号： C12N15/85
CPC分类号： C12N15/86 , C12N2740/13043 , C12N2740/13045 , C12N2810/60
摘要： The current methods of gene therapy do not allow for the efficient transduction of nerve cells, thereby limiting treatment of diseases or disorders involving the nervous system. The present invention is a method of treating a disease or disorder wherein an avian retrovirus (spleen necrosis virus, SNV) is engineered to express a rabies virus glycoprotein that allows for specific targeting of nerve cells. Since SNV is not infectious to human cells the retrovirus of the present invention is safe. Further, incorporation of a glycoprotein gene, specifically the N2C gene, and a therapeutic gene(s) of interest into the retroviral vector allows for the specific and efficient transduction of nerve cells with the gene(s) of interest, thereby treating a disease or disorder involving nerve cells.
摘要翻译：目前的基因治疗方法不能有效地转导神经细胞，从而限制了涉及神经系统的疾病或病症的治疗。本发明是一种治疗疾病或病症的方法，其中将禽类逆转录病毒（脾坏死病毒，SNV）工程化以表达允许神经细胞特异性靶向的狂犬病病毒糖蛋白。由于SNV对人体细胞不感染，所以本发明的逆转录病毒是安全的。此外，将糖蛋白基因，特别是N2C基因和目的基因的治疗基因并入逆转录病毒载体中，允许具有目的基因的神经细胞的特异性和有效转导，从而治疗疾病或涉及神经细胞的病症。

3. 发明申请

WO2003030933A1 RECOMBINANT RABIES VACCINE AND METHODS OF PREPARATION AND USE 审中-公开
标题翻译：重组病毒疫苗及其制备和使用方法
公开(公告)号：WO2003030933A1
公开(公告)日：2003-04-17
申请号：PCT/US2002/032475
申请日：2002-10-10
申请人： THOMAS JEFFERSON UNIVERSITY
发明人： DIETZSCHOLD, Bernard , HOOPER, Craig, D. , SCHNELL, Matthias, J.
IPC分类号： A61K39/205
CPC分类号： A61K39/205 , A61K39/12 , A61K2039/5254 , C12N2760/20134
摘要： Live rabies virus vaccines comprising a recombinant rabies virus genome which overexpresses the rabies virus G protein increase apoptotic activity in infected cells, and enhance the generation of anti-rabies immunity in a subject.
摘要翻译：包含过表达狂犬病病毒G蛋白的重组狂犬病病毒基因组的活狂犬病毒疫苗增加感染细胞中的凋亡活性，并增强受试者中抗狂犬病免疫的产生。

4. 发明申请

WO2002089728A2 RECOMBINANT RHABDOVIRUSES AS LIVE-VIRAL VACCINES 审中-公开
标题翻译：作为活体病毒的重组人RHABDOVIRUSES
公开(公告)号：WO2002089728A2
公开(公告)日：2002-11-14
申请号：PCT/US2002/012637
申请日：2002-04-19
申请人： THOMAS JEFFERSON UNIVERSITY
发明人： SCHNELL, Matthias, J. , POMERANTZ, Roger, J.
IPC分类号： A61K
CPC分类号： C07K14/005 , A61K2039/545 , A61K2039/57 , C07K2319/00 , C12N7/00 , C12N15/86 , C12N2710/24143 , C12N2710/24164 , C12N2740/15022 , C12N2740/16122 , C12N2760/20122 , C12N2760/20143 , C12N2770/24222
摘要： This invention provides recombinant, replication-competent Rhabdovirus vaccine strain-based expression vectors for expressing heterologous viral antigenic polypeptides such as immunodeficiency virus envelope proteins or subparts thereof. An additional transcription stop/start unit within the Rhabdovirus genome is inserted to express the heterologous antigenic polypeptides. The HIV-1 gp160 protein is stably and functionally expressed, as indicated by fusion of human T cell-lines after infection with the recombinant RVs. Inoculation of mice with the recombinant Rabies viruses expressing HIV-1 gp160 induces a strong humoral response directed against the HIV-1 envelope protein after a single boost with an isolated recombinant HIV-1 gp120 protein. Moreover, high neutralization titers, up to 1:800, against HIV-1 are detected in the mouse sera. These recombinant viral vectors expressing viral antigenic polypeptides provide useful and effective pharmaceutical compositions for the generation of viral-specific immune responses.
摘要翻译：本发明提供用于表达异源病毒抗原性多肽（例如免疫缺陷病毒包膜蛋白或其子部分）的重组，基于复制能力的基于弹状病毒基因毒株的表达载体。插入Rhabdovirus基因组内的另外的转录停止/起始单位以表达异源抗原多肽。 HIV-1 gp160蛋白质是稳定和功能表达的，如通过重组RV感染后的人T细胞系的融合所表明的。用重组的表达HIV-1 gp160的狂犬病病毒接种小鼠，用分离的重组HIV-1 gp120蛋白单次加强后，诱导针对HIV-1包膜蛋白的强烈体液应答。此外，在小鼠血清中检测到针对HIV-1的高达1：800的高中和滴度。表达病毒抗原多肽的这些重组病毒载体提供用于产生病毒特异性免疫应答的有用和有效的药物组合物。

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