公开(公告)号：US20050014166A1

公开(公告)日：2005-01-20

申请号：US10720987

申请日：2003-11-24

申请人： Didier Trono ,  Maciej Wiznerowicz

发明人： Didier Trono ,  Maciej Wiznerowicz

IPC分类号： A61K48/00 ,  C12N15/11 ,  C12N15/113 ,  C12N15/86 ,  C12N15/867 ,  C12Q1/68

CPC分类号： C12N15/8509 ,  A01K2217/05 ,  A61D19/04 ,  C12N15/111 ,  C12N15/113 ,  C12N15/86 ,  C12N2310/111 ,  C12N2310/14 ,  C12N2320/32 ,  C12N2320/50 ,  C12N2740/16043 ,  C12N2800/30 ,  C12N2830/003 ,  C12N2830/005 ,  C12N2830/008 ,  C12N2830/48 ,  C12N2830/50 ,  C12N2840/203

摘要： The present invention provides compositions and methods of modulating or regulating eukaryotic gene expression through the controlled or regulated expression of polynucleotide constructs that encode siRNA or other desired exogenous nucleic acids or proteins. Such constructs, and additional elements of the system may be transfected into the cells of interest and the expression of the siRNA, and hence the expression of the target gene of the siRNA, may be controlled through the administration of a compound to the cell, such as a small molecule or drug. Lentivirus vectors are employed in some embodiments of the invention including the generation of conditional knockdown animals.

摘要翻译： 本发明提供了通过控制或调控表达编码siRNA或其它所需外源核酸或蛋白质的多核苷酸构建体来调节或调节真核基因表达的组合物和方法。 可以将这样的构建体和系统的另外的元件转染到感兴趣的细胞中，并且可以通过向细胞施用化合物来控制siRNA的表达，从而siRNA的靶基因的表达，例如 作为小分子或药物。 在本发明的一些实施方案中使用慢病毒载体，包括产生条件性敲除动物。

公开(公告)号：US20070196922A1

公开(公告)日：2007-08-23

申请号：US11680414

申请日：2007-02-28

申请人： Didier Trono ,  Maciej Wiznerowicz

发明人： Didier Trono ,  Maciej Wiznerowicz

IPC分类号： C12N15/867 ,  C12N5/08

CPC分类号： C12N15/86 ,  A61K48/00 ,  C07K14/55 ,  C07K14/70503 ,  C07K16/00 ,  C07K2317/622 ,  C07K2319/30 ,  C12N2740/15043 ,  C12N2740/16043 ,  C12N2800/30 ,  C12N2830/00 ,  C12N2830/002 ,  C12N2830/008 ,  C12N2830/30 ,  C12N2830/48 ,  C12N2830/50 ,  C12N2830/85 ,  C12N2840/20 ,  C12N2840/44

摘要： The present invention provides HIV-derived lentivectors which are safe, highly efficient, and very potent for expressing transgenes for human gene therapy, especially, in human hematopoietic progenitor cells as well as in all other blood cell derivatives. The lentiviral vectors comprise promoters active to promote expression specific to cell types or tissues. Further, promoters are providing that are amenable to control by activators, enhancers, or repressors. These vectors are in a self-inactivating configuration for biosaftey. Additional promoters are also described. The vectors can also comprise additional transcription enhancing elements such as the wood chuck hepatitis virus post-transcriptional regulatory element, without any decrease in the specificity or control exerted by the promoters. These vectors therefore provide useful tools for genetic treatments such as inherited and acquired lympho-hematological disorders, gene-therapies for cancers especially the hematological cancers, as well as for the study of hematopoiesis via lentivector-mediated modification of human HSCs.

摘要翻译： 本发明提供了用于人基因治疗特别是人类造血祖细胞以及所有其他血液细胞衍生物中表达转基因的安全，高效和非常有效的HIV衍生的慢病毒药物。 慢病毒载体包含促进对细胞类型或组织特异性表达的活性的启动子。 此外，提供可由活化剂，增强剂或阻遏物控制的启动子。 这些载体是生物燃料的自灭活配置。 还描述了另外的启动子。 载体还可以包含额外的转录增强元件，例如木卡因肝炎病毒转录后调节元件，而启动子所引起的特异性或对照的任何降低。 因此，这些载体为遗传治疗提供了有用的工具，例如遗传和获得性淋巴 - 血液学障碍，癌症特别是血液癌症的基因治疗，以及通过慢性介导的人类HSC修饰研究造血功能。

公开(公告)号：US08748169B2

公开(公告)日：2014-06-10

申请号：US11680414

申请日：2007-02-28

申请人： Didier Trono ,  Maciej Wiznerowicz

发明人： Didier Trono ,  Maciej Wiznerowicz

IPC分类号： C12N15/63 ,  C12N15/85

CPC分类号： C12N15/86 ,  A61K48/00 ,  C07K14/55 ,  C07K14/70503 ,  C07K16/00 ,  C07K2317/622 ,  C07K2319/30 ,  C12N2740/15043 ,  C12N2740/16043 ,  C12N2800/30 ,  C12N2830/00 ,  C12N2830/002 ,  C12N2830/008 ,  C12N2830/30 ,  C12N2830/48 ,  C12N2830/50 ,  C12N2830/85 ,  C12N2840/20 ,  C12N2840/44

摘要： The present invention provides HIV-derived lentivectors which are safe, highly efficient, and very potent for expressing transgenes for human gene therapy, especially, in human hematopoietic progenitor cells as well as in all other blood cell derivatives. The lentiviral vectors comprise promoters active to promote expression specific to cell types or tissues. Further, promoters are providing that are amenable to control by activators, enhancers, or repressors. These vectors are in a self-inactivating configuration for biosaftey. Additional promoters are also described. The vectors can also comprise additional transcription enhancing elements such as the wood chuck hepatitis virus post-transcriptional regulatory element, without any decrease in the specificity or control exerted by the promoters. These vectors therefore provide useful tools for genetic treatments such as inherited and acquired lympho-hematological disorders, gene-therapies for cancers especially the hematological cancers, as well as for the study of hematopoiesis via lentivector-mediated modification of human HSCs.

摘要翻译： 本发明提供了用于人基因治疗特别是人类造血祖细胞以及所有其他血液细胞衍生物中表达转基因的安全，高效和非常有效的HIV衍生的慢病毒药物。 慢病毒载体包含促进对细胞类型或组织特异性表达的活性的启动子。 此外，提供可由活化剂，增强剂或阻遏物控制的启动子。 这些载体是生物燃料的自灭活配置。 还描述了另外的启动子。 载体还可以包含额外的转录增强元件，例如木卡因肝炎病毒转录后调节元件，而启动子所引起的特异性或对照的任何降低。 因此，这些载体为遗传治疗提供了有用的工具，例如遗传和获得性淋巴 - 血液学障碍，癌症特别是血液癌症的基因治疗，以及通过慢性介导的人类HSC修饰研究造血功能。

公开(公告)号：US20130096370A1

公开(公告)日：2013-04-18

申请号：US13448580

申请日：2012-04-17

申请人： Didier Trono ,  Maciej Wiznerowicz

发明人： Didier Trono ,  Maciej Wiznerowicz

IPC分类号： C12N15/85 ,  A61D19/04

CPC分类号： C12N15/8509 ,  A01K2217/05 ,  A61D19/04 ,  C12N15/111 ,  C12N15/113 ,  C12N15/86 ,  C12N2310/111 ,  C12N2310/14 ,  C12N2320/32 ,  C12N2320/50 ,  C12N2740/16043 ,  C12N2800/30 ,  C12N2830/003 ,  C12N2830/005 ,  C12N2830/008 ,  C12N2830/48 ,  C12N2830/50 ,  C12N2840/203

摘要： The present invention provides compositions and methods of modulating or regulating eukaryotic gene expression through the controlled or regulated expression of polynucleotide constructs that encode siRNA or other desired exogenous nucleic acids or proteins. Such constructs, and additional elements of the system may be transfected into the cells of interest and the expression of the siRNA, and hence the expression of the target gene of the siRNA, may be controlled through the administration of a compound to the cell, such as a small molecule or drug. Lentivirus vectors are employed in some embodiments of the invention including the generation of conditional knockdown animals.

摘要翻译： 本发明提供了通过控制或调控表达编码siRNA或其它所需外源核酸或蛋白质的多核苷酸构建体来调节或调节真核基因表达的组合物和方法。 可以将这样的构建体和系统的另外的元件转染到感兴趣的细胞中，并且可以通过向细胞施用化合物来控制siRNA的表达，从而siRNA的靶基因的表达，例如 作为小分子或药物。 在本发明的一些实施方案中使用慢病毒载体，包括产生条件性敲除动物。

公开(公告)号：US20110172120A1

公开(公告)日：2011-07-14

申请号：US11774177

申请日：2007-07-06

申请人： Didier Trono ,  Maciej Wiznerowicz

发明人： Didier Trono ,  Maciej Wiznerowicz

IPC分类号： C40B40/02 ,  C40B40/06 ,  C40B40/00

CPC分类号： C12N15/8509 ,  A01K2217/05 ,  A61D19/04 ,  C12N15/111 ,  C12N15/113 ,  C12N15/86 ,  C12N2310/111 ,  C12N2310/14 ,  C12N2320/32 ,  C12N2320/50 ,  C12N2740/16043 ,  C12N2800/30 ,  C12N2830/003 ,  C12N2830/005 ,  C12N2830/008 ,  C12N2830/48 ,  C12N2830/50 ,  C12N2840/203

摘要： The present invention provides compositions and methods of modulating or regulating eukaryotic gene expression through the controlled or regulated expression of polynucleotide constructs that encode siRNA or other desired exogenous nucleic acids or proteins. Such constructs, and additional elements of the system may be transfected into the cells of interest and the expression of the siRNA, and hence the expression of the target gene of the siRNA, may be controlled through the administration of a compound to the cell, such as a small molecule or drug. Lentivirus vectors are employed in some embodiments of the invention including the generation of conditional knockdown animals.

摘要翻译： 本发明提供了通过控制或调控表达编码siRNA或其它所需外源核酸或蛋白质的多核苷酸构建体来调节或调节真核基因表达的组合物和方法。 可以将这样的构建体和系统的另外的元件转染到感兴趣的细胞中，并且可以通过向细胞施用化合物来控制siRNA的表达，从而siRNA的靶基因的表达，例如 作为小分子或药物。 在本发明的一些实施方案中使用慢病毒载体，包括产生条件性敲除动物。

公开(公告)号：US07198950B2

公开(公告)日：2007-04-03

申请号：US10261078

申请日：2002-09-30

申请人： Didier Trono ,  Maciej Wiznerowicz

发明人： Didier Trono ,  Maciej Wiznerowicz

IPC分类号： C12N15/867 ,  C12N15/63 ,  C12N15/64 ,  C12N5/10 ,  A61K48/00

CPC分类号： C12N15/86 ,  A61K48/00 ,  C07K14/55 ,  C07K14/70503 ,  C07K16/00 ,  C07K2317/622 ,  C07K2319/30 ,  C12N2740/15043 ,  C12N2740/16043 ,  C12N2800/30 ,  C12N2830/00 ,  C12N2830/002 ,  C12N2830/008 ,  C12N2830/30 ,  C12N2830/48 ,  C12N2830/50 ,  C12N2830/85 ,  C12N2840/20 ,  C12N2840/44

摘要： The present invention provides HIV-derived lentivectors which are safe, highly efficient, and very potent for expressing transgenes for human gene therapy, especially, in human hematopoietic progenitor cells as well as in all other blood cell derivatives. The lentiviral vectors comprise promoters active to promote expression specific to cell types or tissues. Further, promoters are providing that are amenable to control by activators, enhancers, or repressors. These vectors are in a self-inactivating configuration for biosaftey. Additional promoters are also described. The vectors can also comprise additional transcription enhancing elements such as the wood chuck hepatitis virus post-transcriptional regulatory element, without any decrease in the specificity or control exerted by the promoters. These vectors therefore provide useful tools for genetic treatments such as inherited and acquired lympho-hematological disorders, gene-therapies for cancers especially the hematological cancers, as well as for the study of hematopoiesis via lentivector-mediated modification of human HSCs.

摘要翻译： 本发明提供了用于人基因治疗特别是人类造血祖细胞以及所有其他血液细胞衍生物中表达转基因的安全，高效和非常有效的HIV衍生的慢病毒药物。 慢病毒载体包含促进对细胞类型或组织特异性表达的活性的启动子。 此外，提供可由活化剂，增强剂或阻遏物控制的启动子。 这些载体处于生物安全性的自灭活配置。 还描述了另外的启动子。 载体还可以包含额外的转录增强元件，例如土拨鼠肝炎病毒转录后调节元件，而启动子所发挥的特异性或对照的作用没有任何降低。 因此，这些载体为遗传治疗提供了有用的工具，例如遗传和获得性淋巴 - 血液学障碍，癌症特别是血液癌症的基因治疗，以及通过慢性介导的人类HSC修饰研究造血功能。