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公开(公告)号：US5681746A
公开(公告)日：1997-10-28
申请号：US366851
申请日：1994-12-30
IPC分类号： C12N15/09 , A61K35/76 , A61K48/00 , A61P7/00 , C07K14/755 , C12N5/10 , C12N7/00 , C12N15/867 , C12R1/92 , C12N5/00 , C07H21/04 , C12N15/63
CPC分类号： C12N15/86 , C07K14/755 , A61K48/00 , C12N2740/13043
摘要： Retroviral vectors for directing expression of full length factor VIII in transduced host cells, plasmids encoding the same, and host cells transformed, transfected, or transduced therewith are disclosed. Also disclosed are retroviral particles comprising such retrovital vectors, as are methods for making such particles in suitable packaging cells. Retroviral particles so produced may be amphotropic, ecotropic, polytropic, or xenotropic; alternatively, they may comprise chimeric or hybrid envelope proteins to alter host range. Also described are retrovital particles comprising retroviral vectors for directing full length factor VIII expression which are complement resistant. Pharmaceutical compositions comprising retrovital particles of the invention are also disclosed, as are methods of treating mammals, particularly humans, afflicted with hemophilia.
摘要翻译： 公开了用于在转导的宿主细胞中指导全长因子VIII表达的逆转录病毒载体，编码它们的质粒和转化，转染或转导的宿主细胞。 还公开了包含这种逆转录病毒载体的逆转录病毒颗粒，以及在合适的包装细胞中制备这种颗粒的方法。 如此产生的逆转录病毒颗粒可以是单调性，亲和性，多变性或异位性; 或者，它们可以包含嵌合或杂合包膜蛋白以改变宿主范围。 还描述了包含用于引导补体抗性的全长因子VIII表达的逆转录病毒载体的逆转颗粒。 还公开了包含本发明的逆转录病毒颗粒的药物组合物，以及治疗患有血友病的哺乳动物，特别是人的方法。
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公开(公告)号：US06333195B1
公开(公告)日：2001-12-25
申请号：US09479776
申请日：2000-01-07
申请人： James G. Respess , Nicholas J. DePolo , Sunil Chada , Sybille Sauter , Mordechai Bodner , David A. Driver
发明人： James G. Respess , Nicholas J. DePolo , Sunil Chada , Sybille Sauter , Mordechai Bodner , David A. Driver
IPC分类号： C12N15867
CPC分类号： C12N15/86 , C12N2740/13043 , C12N2740/13052
摘要： Retroviral vector constructs are described which have a 5′ LTR, a tRNA binding site, a packaging signal, one or more heterologous sequences, an origin of second strand synthesis and a 3′ LTR, wherein the vector construct lacks retroviral gag/pol or env coding sequences. In addition, gag/pol, and env expression cassettes are described wherein the expression cassettes lack a consecutive sequence of more than 8 nucleotides in common. The above-described retroviral vector constructs, gag/pol and env expression cassettes may be utilized to construct producer cell lines which preclude the formation of replication competent virus.
摘要翻译： 描述了具有5'LTR，tRNA结合位点，包装信号，一个或多个异源序列，第二链合成起始和3'LTR的逆转录病毒载体构建体，其中载体构建体缺乏逆转录病毒gag / pol或env 编码序列。 此外，描述了gag / pol和env表达盒，其中表达盒缺少共同超过8个核苷酸的连续序列。 上述逆转录病毒载体构建体，gag / pol和env表达盒可用于构建排除形成复制能力的病毒的生产细胞系。
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公开(公告)号：US6013517A
公开(公告)日：2000-01-11
申请号：US850961
申请日：1997-05-05
申请人： James G. Respess , Nicholas J. DePolo , Sunil Chada , Sybille Sauter , Mordechai Bodner , David A. Driver
发明人： James G. Respess , Nicholas J. DePolo , Sunil Chada , Sybille Sauter , Mordechai Bodner , David A. Driver
IPC分类号： C12N15/48 , C12N15/867 , C12N5/10 , C12N15/86
CPC分类号： C12N15/86 , C12N2740/13043 , C12N2740/13052
摘要： Retroviral vector constructs are described which have a 5' LTR, a tRNA binding site, a packaging signal, one or more heterologous sequences, an origin of second strand synthesis and a 3' LTR, wherein the vector construct lacks retroviral gag/pol or env coding sequences. In addition, gag/pol, and env expression-cassettes are described wherein the expression cassettes lack a consecutive sequence of more than 8 nucleotides in common. The above-described retroviral vector constructs, gag/pol and env expression cassettes may be utilized to construct producer cell lines which preclude the formation of replication competent virus.
摘要翻译： 描述了具有5'LTR，tRNA结合位点，包装信号，一个或多个异源序列，第二链合成起始和3'LTR的逆转录病毒载体构建体，其中该载体构建体缺乏逆转录病毒gag / pol或env 编码序列。 此外，描述了gag / pol和env表达盒，其中表达盒缺少多于8个核苷酸的连续序列。 上述逆转录病毒载体构建体，gag / pol和env表达盒可用于构建排除形成复制能力的病毒的生产细胞系。
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4.发明授权Methods for producing a vector producing cell line utilizing a high multiplicity of transduction 有权利用高转化率产生产生生物体的细胞系的方法公开(公告)号：US06410316B1
公开(公告)日：2002-06-25
申请号：US09526983
申请日：2000-03-15
申请人： Philip L. Sheridan , Mordechai Bodner , Nicholas J. DePolo , Sybille Sauter , Stephen M. W. Chang
发明人： Philip L. Sheridan , Mordechai Bodner , Nicholas J. DePolo , Sybille Sauter , Stephen M. W. Chang
IPC分类号： C12N1500
CPC分类号： C12N7/00 , A61K48/00 , A61K48/0091 , C07K14/005 , C12N15/86 , C12N2740/13022 , C12N2740/13043 , C12N2740/13052 , C12N2760/20134 , C12N2760/20222
摘要： Retroviral vector particle producing cells are provided, wherein the cell (a) has greater than 5 stably integrated copies of a retroviral vector construct; (b) produces greater than 10 infectious recombinant retroviral vector particles per cell per day; and (c) produces replication incompetent retroviral vector particles.
摘要翻译： 提供了逆转录病毒载体产生细胞，其中细胞（a）具有大于5个逆转录病毒载体构建体的稳定整合的拷贝; （b）每个细胞每天产生大于10个感染性重组逆转录病毒载体颗粒; 和（c）产生复制无能的逆转录病毒载体颗粒。
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5.发明授权Methods and compositions for increasing the infectivity of gene transfer vectors 失效增加基因转移载体感染性的方法和组合物公开(公告)号：US06855549B1
公开(公告)日：2005-02-15
申请号：US09448613
申请日：1999-11-22
申请人： Paul B. McCray, Jr. , Guoshun Wang , Beverly Davidson , Mordechai Bodner , Steven M. Herrmann , Douglas J. Jolly
发明人： Paul B. McCray, Jr. , Guoshun Wang , Beverly Davidson , Mordechai Bodner , Steven M. Herrmann , Douglas J. Jolly
CPC分类号： A61K48/0008 , A61K9/0073 , A61K47/183 , A61K48/00 , C07K14/4712 , C12N2799/025 , C12N2799/027
摘要： The present invention involves methods and compositions for increasing the susceptibility of target cells to transduction by gene transfer vectors. Specifically, it is proposed that increasing intracellular permeability in epithelial tissue increases the percentage of input vector that will transduce that target tissue. Specific examples show that receptors for retrovirus are preferentially accessible on the basolateral surface of airway epithelia, and permeabilizing such tissues results in greater infection with retrovirus. This has important implications in gene therapy, for example, to treat cystic fibrosis with the CFTR gene.
摘要翻译： 本发明涉及通过基因转移载体增加靶细胞对转导的敏感性的方法和组合物。 具体来说，提出增加上皮组织中的细胞内通透性增加了将转导该靶组织的输入载体的百分比。 具体实例表明，逆转录病毒的受体优先在气道上皮的基底外侧表面可及，并且透化这样的组织导致逆转录病毒感染更大。 这在基因治疗中具有重要意义，例如用CFTR基因治疗囊性纤维化。
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公开(公告)号：US5693522A
公开(公告)日：1997-12-02
申请号：US371922
申请日：1995-01-11
IPC分类号： C12N15/09 , A61K39/00 , A61K48/00 , A61P35/00 , C07K14/00 , C07K14/47 , C07K14/82 , C12N5/10 , C12N15/00 , C07H21/02 , C12N5/00
摘要： The present invention provides a method of destroying selected tumor cells comprising administering to a warm-blooded animal a vector construct which directs the expression of at least one immunogenic, non-tumorigenic form of an altered cellular component normally associated with the selected tumor cells. Also provided are vector constructs which direct the expression of altered cellular components. Representative altered cellular components include ras.sup.*, p53.sup.*, Rb.sup.*, alter protein encoded by the Wilms' tumor gene, ubiquitin.sup.*, mucin.sup.*, DCC, APC, MCC, neu, an altered receptor, and bcr/abl. Also provided are recombinant viruses carrying a vector construct, target cells infected with the recombinant virus, and pharmaceutical compositions comprising the recombinant virus and a pharmaceutically acceptable carrier or diluent.
摘要翻译： 本发明提供了破坏所选择的肿瘤细胞的方法，包括向温血动物施用指导至少一种免疫原性，非致瘤性形式的通常与所选择的肿瘤细胞相关的改变的细胞组分的载体构建体。 还提供了引导改变的细胞组分的表达的载体构建体。 代表性改变的细胞成分包括由Wilms肿瘤基因编码的ras *，p53 *，Rb *，改变的蛋白质，泛素*，粘蛋白*，DCC，APC，MCC，neu，改变的受体和bcr / abl。 还提供携带载体构建体的重组病毒，用重组病毒感染的靶细胞，以及包含重组病毒和药学上可接受的载体或稀释剂的药物组合物。
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