公开(公告)号：EP1412493A2

公开(公告)日：2004-04-28

申请号：EP02763401.3

申请日：2002-08-01

申请人： RESEARCH DEVELOPMENT FOUNDATION

发明人： TRONO, Didier ,  ZUFFEREY, Romain, N.

IPC分类号： C12N15/00

CPC分类号： C12N15/86 ,  A61K48/00 ,  C12N7/00 ,  C12N2740/15043 ,  C12N2740/16043 ,  C12N2740/16052 ,  C12N2740/16061 ,  C12N2830/38 ,  C12N2830/48 ,  C12N2830/50 ,  C12N2840/203 ,  C12N2840/44

摘要： The present invention provides HIV-derived lentivectors which are multiply modified to create highly safe, efficient, and potent vectors for expressing transgenes for gene therapy. The lentiviral vector comprise various combinations of an inactive central polypurine tract, a stuffer sequence, which may encode drug susceptibility genes, and a mutated hairpin in the 5' leader sequence that substantially abolishes replication. These elements are provided in conjunction with other features of lentiviral vectors, such as a self-inactivating configuration for biosaftey and promoters such as the EF1α promoter as one example. 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. These vectors therefore provide useful tools for genetic treatments for inherited and acquired disorders, gene-therapies for cancers and other disease, the creation of industrial and experimental production systems utilizing transformed cells, as well as for the study of basic cellular and genetic processes.

公开(公告)号：EP1383891A2

公开(公告)日：2004-01-28

申请号：EP02733179.2

申请日：2002-04-19

申请人： ADEREGEM (Association pour le Développement de la Recherche en Génétique Moléculaire

发明人： CHAMBON, Pierre ,  GHYSELINCK, Norbert, B. ,  SCHNÜTGEN, Frank

IPC分类号： C12N15/11 ,  C12N15/09 ,  C12N15/63 ,  C12N15/90 ,  C12N5/10 ,  C12N1/21 ,  C12N1/19 ,  A01H5/00 ,  A01K67/027

CPC分类号： C12N15/90 ,  C12N15/63 ,  C12N2800/30 ,  C12N2800/60 ,  C12N2840/20 ,  C12N2840/203 ,  C12N2840/44

摘要： The invention relates to a method for the stable inversion of a DNA fragment upon recombinase-mediated rearrangements using two sets of two incompatible site-specific recombinase targeting sites (SSRTS) in the same order but in reverse orientation flanking said DNA fragment to be inverted. The invention also relates to a method for the stable inversion of said DNA fragment upon rearrangement mediated by a recombinase such as Cre recombinase. The invention also relates to a method for obtaining a transgenic cell of which at least one allele of a DNA sequence of interest is invalidated by a process of conditional deletion and the genome of which comprises a reporter gene inserted at the place of the DNA fragment deleted by said process of conditional deletion. The invention also concerns a method to generate targeting sites to perform site-specific recombination mediated cassette exchange. The corresponding vectors, host cells, and transgenic animals are claimed.

公开(公告)号：EP1360191A2

公开(公告)日：2003-11-12

申请号：EP02704234.0

申请日：2002-01-24

申请人： Setagon, Inc.

发明人： OWENS, Gary K. ,  MANABE, Ichiro

IPC分类号： C07H21/04 ,  A01K67/00 ,  C12N15/74 ,  C12N15/85 ,  C12Q1/68

CPC分类号： C12N15/85 ,  A01K2217/05 ,  A61K48/00 ,  C12N2830/008 ,  C12N2830/85 ,  C12N2840/44

摘要： The present invention generally relates to promoters, enhancers and other regulatory elements of smooth muscle cells ('SMC'). The invention more particularly relates to methods for the targeted knockout, or over-expression, of genes of interest within smooth muscle cells or within a subtype of smooth muscle cells. The invention further relates to methods of conferring polynucleotide expression in vivo specifically in smooth muscle cells or in subtypes of smooth muscle cells.

公开(公告)号：EP1356070A2

公开(公告)日：2003-10-29

申请号：EP01973503.4

申请日：2001-09-21

申请人： Virxsys

发明人： CHANG, Yung-Nien ,  LU, Xiaobin ,  SLEPUSHKIN, Vladimir ,  CONDE, Betty ,  DAVIS, Brian ,  YU, Qiao ,  YANG, Yanping ,  MERLING, Randal ,  HAN, Wei ,  NI, Yajin ,  LI, Yuexia ,  DROPULIC, Boro

IPC分类号： C12N15/86

CPC分类号： C12N15/86 ,  A61K48/00 ,  C12N2740/16043 ,  C12N2800/108 ,  C12N2830/40 ,  C12N2830/42 ,  C12N2830/48 ,  C12N2830/50 ,  C12N2840/20 ,  C12N2840/203 ,  C12N2840/44

摘要： The present invention provides improved conditionally replicating vectors that have improved safety against the generation of replication competent vectors or virus. Also disclosed are methods of making, propagating and selectively packaging, modifying, and using such vectors. Included are improved helper constructs, host cells, for use with the improved vectors as well as pharmaceutical compositions and host cells comprising the vectors, the use of vector containing host cells to screen drugs, and methods of using the vectors to determine gene function. The methods also include the prophylatic and therapeutic treatment of disease, especially viral infection, and HIV infection in particular.

公开(公告)号：EP0877752B1

公开(公告)日：2003-05-21

申请号：EP97903068.1

申请日：1997-01-23

申请人： THE BOARD OF TRUSTEES OF THE LELAND STANFORD JUNIOR UNIVERSITY ,  Rigel Pharmaceuticals, Inc.

发明人： NOALN, Garry P. ,  ROTHENBERG, S. Michael

IPC分类号： C07K1/04 ,  C12N15/86 ,  C12Q1/02 ,  C12Q1/68 ,  C12Q1/70

CPC分类号： C12N15/1082 ,  C07K1/047 ,  C12N15/1034 ,  C12N15/1079 ,  C12N15/86 ,  C12N2740/13043 ,  C12N2799/027 ,  C12N2830/00 ,  C12N2830/85 ,  C12N2840/20 ,  C12N2840/203 ,  C12N2840/44 ,  C12Q1/6811 ,  C12Q1/6897 ,  C12Q1/70 ,  G01N33/5008 ,  G01N33/5011 ,  G01N33/5014 ,  G01N33/5041 ,  G01N33/5044 ,  G01N33/5064 ,  G01N33/68 ,  G01N33/6803 ,  G01N2500/00 ,  G01N2510/00

摘要： Methods and compositions for screening for transdominant effector peptides and RNA molecules selected inside living cells from randomized pools are provided.

摘要翻译： 提供了用于筛选来自随机池的活细胞内选择的转移性效应子肽和RNA分子的方法和组合物。

公开(公告)号：EP1264892A2

公开(公告)日：2002-12-11

申请号：EP02011588.7

申请日：2002-05-27

申请人： Universita' Di Torino

发明人： Naldini, Luigi ,  De Palma, Michele

IPC分类号： C12N15/867 ,  C12N15/63 ,  C12N15/90 ,  A61K48/00

CPC分类号： C12N15/86 ,  A61K48/00 ,  C12N2740/16043 ,  C12N2830/008 ,  C12N2830/48 ,  C12N2830/50 ,  C12N2830/85 ,  C12N2840/203 ,  C12N2840/44

摘要： A lentiviral vector construct for transferring nucleotide sequences in vivo and ex vivo , which comprises transcription regulatory sequences of one or more genes preferentially expressed in endothelial cells of mammals, particularly sequences of the intronic and promoter regions of one or more human and murine genes preferentially expressed in endothelial cells. The invention also relates to the use of a lentiviral vector construct according to the invention for manufacturing a preparation for treating an angiogenesis-related pathology by gene delivery and selective expression in cells engaged in angiogenesis.

摘要翻译： 一种用于在体内和体外转移核苷酸序列的慢病毒载体构建体，其包含优先在哺乳动物的内皮细胞中表达的一个或多个基因的转录调节序列，特别是优先表达的一个或多个人和鼠基因的内含子和启动子区的序列 在内皮细胞中。 本发明还涉及根据本发明的慢病毒载体构建体在制备用于通过基因递送和在从事血管发生的细胞中的选择性表达来治疗血管生成相关病理学的制剂的用途。

公开(公告)号：EP1220928A2

公开(公告)日：2002-07-10

申请号：EP00967217.1

申请日：2000-10-02

申请人： ALEXION PHARMACEUTICALS, INC.

发明人： FODOR, William, L. ,  RAMSOONDAR, Jagdeece, J.

IPC分类号： C12N15/54 ,  C12N15/90 ,  C12N15/63 ,  C12N15/67 ,  C12N15/85 ,  C12N9/10 ,  C12N5/10 ,  C12N1/21 ,  A01K67/027

CPC分类号： A01K67/0275 ,  A01K2217/05 ,  A01K2217/075 ,  C12N9/10 ,  C12N15/63 ,  C12N15/67 ,  C12N15/85 ,  C12N15/902 ,  C12N15/907 ,  C12N2800/60 ,  C12N2830/42 ,  C12N2840/44

摘要： Disclosed are novel compositions and methods useful for modulating expression of a target gene in a cell by insertion of exogenous DNA sequence into the target gene. The compositions and methods of the invention are useful for generation of knockout animals including mammals.

公开(公告)号：EP1199368A2

公开(公告)日：2002-04-24

申请号：EP01124236.9

申请日：1999-07-01

申请人： TRANSGENE S.A.

发明人： Mehtali, Majid ,  Lusky, Monika

IPC分类号： C12N15/861 ,  C12N15/34 ,  C07K14/075 ,  C12N7/01 ,  C12N5/10 ,  A61K48/00

CPC分类号： C12N15/86 ,  A61K48/00 ,  C07K14/005 ,  C12N2710/10322 ,  C12N2710/10343 ,  C12N2830/008 ,  C12N2840/44

摘要： Described are recombinant adenoviral vectors retaining sufficient E4 sequences to improve the expression and/or persistence of expression of a gene of interest. Furthermore, the invention describes the use of a polynucleotide encoding one or more ORF(s) of the E4 region of an adenovirus selected from ORF1, ORF2, ORF3, ORF4, ORF3/4, ORF6/7, ORF6 and ORF7 taken individually or in combination, to improve the expression and/or persistence of expression of a gene of interest operably linked to regulatory elements and inserted into an expression vector. Finally, a host cell, a composition, an infectious viral particle comprising such a polynucleotide or adenoviral vector, a method for preparing said viral particle as well as their therapeutic use are described.

公开(公告)号：EP1155131A2

公开(公告)日：2001-11-21

申请号：EP00908750.3

申请日：2000-02-22

申请人： Athersys, Inc.

发明人： HARRINGTON, John, J. ,  SHERF, Bruce ,  RUNDLETT, Stephen

IPC分类号： C12N15/67 ,  C12N15/85 ,  C12N15/63 ,  C12Q1/68 ,  C12N15/10 ,  C12N15/62 ,  G01N33/50

CPC分类号： C12N15/1096 ,  C07K2319/00 ,  C12N15/63 ,  C12N15/67 ,  C12N15/85 ,  C12N2800/108 ,  C12N2800/204 ,  C12N2800/60 ,  C12N2840/20 ,  C12N2840/203 ,  C12N2840/44

摘要： The present invention is directed generally to activating gene expression or causing over-expression of a gene by recombination methods in situ. The invention also is directed generally to methods for expressing an endogenous gene in a cell at levels higher than those normally found in the cell. In one embodiment of the invention, expression of an endogenous gene is activated or increased following integration into the cell, by non-homologous or illegitimate recombination, of a regulatory sequence that activates expression of the gene. In another embodiment, the expression of the endogenous gene may be further increased by co-integration of one or more amplifiable markers, and selecting for increased copies of the one or more amplifiable markers located on the integrated vector. In another embodiment, the invention is directed to activation of endogenous genes by non-targeted integration of specialized activation vectors, which are provided by the invention, into the genome of a host cell. The invention also provides methods for the identification, activation, isolation, and/or expression of genes undiscoverable by current methods since no target sequence is necessary for integration. The invention also provides methods for isolation of nucleic acid molecules (particularly cDNA molecules) encoding a variety of proteins, including transmembrane proteins, and for isolation of cells expressing such transmembrane proteins which may be heterologous transmembrane proteins. The invention also is directed to isolated genes, gene products, nucleic acid molecules, to compositions comprising such genes, gene products and nucleic acid molecules, and to vectors and host cells comprising such genes and nucleic acid molecules, that may be used in a variety of therapeutic and diagnostic applications. Thus, by the present invention, endogenous genes, including those associated with human disease and development, may be activated and isolated without prior knowledge of the sequence, structure, function, or expression profile of the genes.

公开(公告)号：EP0952767A4

公开(公告)日：2001-10-24

申请号：EP96942757

申请日：1996-11-12

申请人： UNIV ROCHESTER

发明人： FEDEROFF HOWARD

IPC分类号： A01K67/027 ,  C07K14/48 ,  C12N5/10 ,  C12N9/00 ,  C12N15/09 ,  C12N15/63 ,  C12N15/85 ,  C12N15/869 ,  C12Q1/68 ,  A01K67/00 ,  C12N15/00 ,  C12N15/01 ,  C12N15/10 ,  C12N15/11

CPC分类号： A01K67/0275 ,  A01K67/0276 ,  A01K2217/05 ,  A01K2217/075 ,  A01K2227/105 ,  A01K2267/03 ,  A01K2267/0356 ,  C07K14/48 ,  C12N9/00 ,  C12N15/63 ,  C12N15/85 ,  C12N15/8509 ,  C12N15/86 ,  C12N2710/16643 ,  C12N2800/108 ,  C12N2800/30 ,  C12N2830/008 ,  C12N2840/203 ,  C12N2840/44

摘要： The present invention relates to recombinatorial substrates which include a promoter, a terminator, a gene positioned 3' to the terminator and whose expression is to be controlled, and recombination sites on each side of the terminator such that when the substrate is treated with a specific recombinase the gene will be expressed. Recombinatorial substrates which have a promoter, a gene to be controlled, and recombination sites on each side of the gene which when treated with recombinase delete the gene are also provided. Also enclosed are methods of creating transgenic mammals carrying the recombinatorial substrate and methods for activating the recombinatorial substrate.