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1.发明授权Enhanced packaging of herpes virus amplicons and generation of recombinant virus vectors 失效增强疱疹病毒扩增子的包装和重组病毒载体的产生公开(公告)号：US06573090B1
公开(公告)日：2003-06-03
申请号：US09458068
申请日：1999-12-09
申请人： Xandra O. Breakefield , E. Antonio Chiocca , Yoshinaga Saeki , Cornel Fraefel , Kurt Tobler , Mathias Ackermann , Mark Suter , Gosse J. Adema , Ken Shortman
发明人： Xandra O. Breakefield , E. Antonio Chiocca , Yoshinaga Saeki , Cornel Fraefel , Kurt Tobler , Mathias Ackermann , Mark Suter , Gosse J. Adema , Ken Shortman
IPC分类号： C12N1581
CPC分类号： C12N15/86 , A61K39/00 , A61K39/12 , A61K39/245 , A61K48/00 , A61K2039/5256 , A61K2039/53 , A61K2039/545 , C12N2710/16634 , C12N2710/16643 , C12N2800/204
摘要： The present invention relates to an enhanced and simplified herpes virus amplicon packaging system. The packaging system comprises a herpes virus amplicon vector and a packaging vector. In one embodiment, the packaging vector comprises a bacterial artificial chromosome (BAC) containing the HSV-1 genome. The packaging vector contains an intact pac site but is otherwise rendered packaging defective. The packaging vector can be rendered packaging defective by inserting nucleotides into the pac site, or by otherwise interfering with the capsid's ability to close, for example, by increasing the size of the DNA fragment upon which the herpes virus genome is cloned. This system can be used to package a wide range of nucleotide sequences (e.g., a therapeutic or antigenic gene) into an empty herpes virus particle taking advantage of the large transgene capacity of herpes viruses. This system can also be used as a vaccine to induce protective immunity against HSV-1, or other complex pathogens.
摘要翻译： 本发明涉及增强和简化的疱疹病毒扩增子包装系统。 包装系统包括疱疹病毒扩增子载体和包装载体。 在一个实施方案中，包装载体包含含有HSV-1基因组的细菌人造染色体（BAC）。 包装载体包含完整的pac位点，否则会导致包装有缺陷。 包装载体可以通过将核苷酸插入pac位点而被包装有缺陷，或以其它方式干扰衣壳关闭的能力，例如通过增加克隆疱疹病毒基因组的DNA片段的大小。 该系统可用于利用疱疹病毒的大转基因能力将大范围的核苷酸序列（例如，治疗或抗原基因）包装到空疱疹病毒颗粒中。 该系统也可以用作疫苗来诱导针对HSV-1或其他复杂病原体的保护性免疫。
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公开(公告)号：US06602499B1
公开(公告)日：2003-08-05
申请号：US09302952
申请日：1999-04-30
IPC分类号： A61K3500
CPC分类号： B82Y5/00 , A61K31/675 , A61K35/763 , A61K38/415 , A61K38/44 , A61K45/06 , A61K47/6891 , A61K48/00 , C12N7/00 , C12N15/86 , C12N2710/16332 , C12N2710/16632 , C12N2710/16643 , C12Y114/14 , C12Y117/04001 , A61K2300/00
摘要： The present invention relates to viral mutants and methods of using these viral mutants for selectively killing neoplastic cells. The viral mutants of the invention are capable of selectively killing neoplastic cells by a combination of viral mediated oncolysis and anti-cancer (“suicide”) gene therapy.
摘要翻译： 本发明涉及病毒突变体和使用这些病毒突变体选择性杀死肿瘤细胞的方法。 本发明的病毒突变体能够通过病毒介导的溶瘤和抗癌（“自杀”）基因治疗的组合选择性地杀死肿瘤细胞。
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公开(公告)号：US5688773A
公开(公告)日：1997-11-18
申请号：US330523
申请日：1994-10-28
IPC分类号： C12N15/09 , A61K31/675 , A61K35/76 , A61K38/00 , A61K48/00 , A61P25/00 , A61P35/00 , C12N5/10 , C12N9/02 , C12N5/00 , C12N15/00 , C07N14/00
CPC分类号： C12N9/0079 , A61K48/00 , A61K38/00 , C12N2799/027
摘要： A method for selectively killing nervous system and peripheral neoplastic cells is provided. Viral vectors are used to selectively express a cytochrome P450 gene in neoplastic cells, whose gene product targets the cells for selective killing, by rendering the cells sensitive to a chemotherapeutic agent.
摘要翻译： 提供了选择性地杀死神经系统和外周肿瘤细胞的方法。 病毒载体用于通过使细胞对化学治疗剂敏感的肿瘤细胞中选择性表达细胞色素P450基因，其肿瘤细胞的基因产物靶向选择性杀伤细胞。
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4.发明申请公开(公告)号：US20080152590A1
公开(公告)日：2008-06-26
申请号：US12044204
申请日：2008-03-07
CPC分类号： C12N7/00 , A61K35/12 , A61K38/00 , A61K48/0008 , A61K48/0075 , C12N5/0623 , C12N15/86 , C12N2510/00 , C12N2710/16052 , C12N2710/16643 , C12N2740/10052 , Y02A50/473
摘要： One of the impediments to the treatment of some human brain tumors (e.g. gliomas) has been the degree to which they expand, migrate widely, and infiltrate normal tissue. We demonstrate that a clone of multipotent neural progenitor stem cells, when implanted into an experimental glioma, will migrate along with and distribute themselves throughout the tumor in juxtaposition to widely expanding and aggressively advancing tumor cells, while continuing to express a foreign reporter gene. Furthermore, drawn somewhat by the degenerative environment created just beyond the infiltrating tumor edge, the neural progenitor cells migrate slightly beyond and surround the invading tumor border. When implanted at a distant sight from the tumor bed (e.g., into normal tissue, into the contralateral hemisphere, into the lateral ventricles) the donor neural progenitor/stem cells will migrate through normal tissue and specifically target the tumor cells. These results suggest the adjunctive use of neural progenitor/stem cells as a novel, effective delivery vehicle for helping to target therapeutic genes and vectors to invasive brain tumors that have been refractory to treatment.
摘要翻译： 治疗某些人脑肿瘤（例如神经胶质瘤）的障碍之一是它们扩张，迁移广泛并渗透正常组织的程度。 我们证明，当植入实验性神经胶质瘤时，多潜能神经祖细胞的克隆将与整个肿瘤一起迁移并分布在整个肿瘤中，并与广泛扩张和积极进展的肿瘤细胞并列，同时继续表达外源报告基因。 此外，由于刚刚超出渗透性肿瘤边缘的退化环境，神经祖细胞迁移稍微超出并包围入侵肿瘤边界。 当植入远离肿瘤床（例如，进入正常组织，进入对侧半球，进入侧脑室）时，供体神经祖细胞/干细胞将迁移通过正常组织并且特异性靶向肿瘤细胞。 这些结果表明辅助性使用神经祖细胞/干细胞作为一种新型有效的递送载体，用于帮助将治疗基因和载体靶向治疗难治性的侵袭性脑肿瘤。
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公开(公告)号：US20130029339A1
公开(公告)日：2013-01-31
申请号：US13395354
申请日：2010-09-09
IPC分类号： C12Q1/68
CPC分类号： C12Q1/6886 , C12Q1/6858 , C12Q2600/106 , C12Q2600/118 , C12Q2600/156 , C12Q2527/125
摘要： Microvesicles are small membrane vesicles that either shed or bud off eukarotic cells. Analysis of the nucleic acid content of microvesicles may be useful in detecting the presence or absence of genetic aberrations. This invention discloses novel methods of diagnosing, prognosing, monitoring, or treating a disease, such as cancer, or other medical condition in a subject involving analyzing one or more nucleic acids contained within an isolated microvesicle for the presence or absence of one or more Kras genetic aberrations.
摘要翻译： 微泡是脱落或脱落的真核细胞的小囊泡。 微泡核酸含量的分析可用于检测遗传畸变的存在或不存在。 本发明公开了一种诊断，预后，监测或治疗疾病如癌症或其他医学病症的新方法，所述方法涉及分析一种或多种Kras存在或不存在于分离的微囊中的一种或多种核酸 遗传畸变。
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6.发明申请USE OF MICROVESICLES IN DIAGNOSIS, PROGNOSIS AND TREATMENT OF MEDICAL DISEASES AND CONDITIONS 审中-公开在诊断，预防和治疗医疗疾病和病症方面使用微波技术公开(公告)号：US20110053157A1
公开(公告)日：2011-03-03
申请号：US12865681
申请日：2009-02-02
申请人： Johan Karl Olov Skog , Xandra O. Breakefield , Dennis Brown , Kevin C. Miranda , Leileata M. Russo
发明人： Johan Karl Olov Skog , Xandra O. Breakefield , Dennis Brown , Kevin C. Miranda , Leileata M. Russo
IPC分类号： C12Q1/68
CPC分类号： C12Q1/6883 , C12N15/1017 , C12Q1/6806 , C12Q1/6886 , C12Q2600/106 , C12Q2600/112 , C12Q2600/156 , C12Q2600/158 , C12Q2600/178
摘要： The presently disclosed subject matter is directed to methods of aiding diagnosis, prognosis, monitoring and evaluation of a disease or other medical condition in a′ subject by detecting a biomarker in microvesicles isolated from a biological, sample from the subject. Moreover, disclosed subject matter is directed to methods of diagnosis, monitoring a disease by determining the concentration of microvesicles within a biological sample; methods of delivering a nucleic acid or protein to a target all by administering microvesicles that contain said nucleic acid or protein; methods for performing a body fluid transfusion by introducing a microvesicle-free or microvesicle enriched fluid fraction into a patient.
摘要翻译： 目前公开的主题涉及通过检测从生物样品分离的微泡中的生物标志物来帮助患者的疾病或其他医学状况的诊断，预后，监测和评价的方法。 此外，所公开的主题涉及诊断方法，通过确定生物样品中微泡的浓度来监测疾病; 通过施用含有所述核酸或蛋白质的微泡，将核酸或蛋白质递送至靶标的方法; 通过将无微泡或富含微泡的流体部分引入患者来进行体液输注的方法。
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公开(公告)号：US06770632B1
公开(公告)日：2004-08-03
申请号：US09617116
申请日：2000-07-14
IPC分类号： A61K3170
CPC分类号： A61K45/06 , A61K38/53 , Y02A50/465
摘要： Methods of killing neoplastic cells are provided. The invention relates to the use of folylpolyglutamyl synthetase (FPGS) gene transfer to enhance the sensitivity of several types of tumor cells to polyglutamylatable antifolate drugs, such as methotrexate (MTX) and edatrexate (EDX).
摘要翻译： 提供杀死肿瘤细胞的方法。 本发明涉及使用叶酰基聚谷氨酰合成酶（FPGS）基因转移来增强几种类型的肿瘤细胞对聚谷氨酰化抗叶酸药物如甲氨蝶呤（MTX）和依达曲沙（EDX））的敏感性。
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8.发明授权Herpes simplex virus amplicon vector targeting system and method of using same 失效单纯疱疹病毒扩增子载体靶向系统及其使用方法公开(公告)号：US06673602B1
公开(公告)日：2004-01-06
申请号：US09592537
申请日：2000-06-12
IPC分类号： C12N1500
CPC分类号： C12N15/86 , A61K48/00 , C12N2710/16643 , C12N2710/16645 , C12N2810/40 , C12N2810/60
摘要： The present invention relates to herpes simplex virus (HSV) amplicon vectors, and in particular, HSV-1 amplicon vectors, which have been genetically modified and used alone or with consequent genetically modified HSV virus, to target a selected cell type, such as neoplastic cells. The present invention also relates to methods of using such vectors to target a cell, in order to treat a pathologic condition, such as cancer.
摘要翻译： 本发明涉及单纯疱疹病毒（HSV）扩增子载体，特别是HSV-1扩增子载体，其已被遗传修饰并且单独使用或随后使用遗传修饰的HSV病毒靶向所选择的细胞类型，例如肿瘤 细胞。 本发明还涉及使用这些载体靶向细胞的方法，以便治疗诸如癌症的病理状况。
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公开(公告)号：US5407821A
公开(公告)日：1995-04-18
申请号：US725083
申请日：1991-07-03
IPC分类号： A61K31/13 , A61K31/135 , A61K31/395 , A61K31/415 , A61K31/445 , A61K31/475 , A61K31/54 , A61K45/00 , A61P25/28 , A61P43/00 , C12Q1/68 , C12P19/34
CPC分类号： C12Q1/683 , C12Q1/6883 , C12Q2600/156 , Y10S436/811
摘要： Methods are provided for detecting the presence of a gene for torsion dystonia in a human subject. Furthermore, a haplotype which is associated with torsion dystonia is disclosed. Methods and kits for the detection of torsion dystonia in a subject are additionally provided.
摘要翻译： 提供了用于检测人受试者中扭转肌张力障碍基因存在的方法。 此外，公开了与扭转肌张力障碍相关的单倍型。 还提供了用于检测受试者扭转肌张力障碍的方法和试剂盒。
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公开(公告)号：US20130040833A1
公开(公告)日：2013-02-14
申请号：US13395284
申请日：2010-09-09
CPC分类号： C12Q1/6806 , C12Q2563/161
摘要： The invention concerns gene signatures obtained from microvesicles and a method of applying these gene signatures in helping to determine a biological condition. The determination of a biological condition may aid, for example, the diagnosis, prognosis, and therapy treatment selection for a disease in a subject.
摘要翻译： 本发明涉及从微泡获得的基因特征以及应用这些基因签名帮助确定生物学条件的方法。 生物学条件的测定可以帮助例如对受试者的疾病的诊断，预后和治疗治疗选择。
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