公开(公告)号：WO1996009385A1

公开(公告)日：1996-03-28

申请号：PCT/US1995011873

申请日：1995-09-19

Applicant: MASSACHUSETTS INSTITUTE OF TECHNOLOGY

Inventor： MASSACHUSETTS INSTITUTE OF TECHNOLOGY ,  LEBOULCH, Philippe ,  LONDON, Irving, M.

IPC: C12N15/12

CPC classification number: C07K14/805 ,  A01K2217/05 ,  A61K38/00 ,  C12N2799/027

Abstract: Gene therapy methods and compositions for high level expression of anti-sickling beta-globin proteins in erythroid cells for treating Sickle Cell Disease are described.

Abstract translation: 描述了用于治疗镰状细胞病的红细胞中抗镰状β-珠蛋白高水平表达的基因治疗方法和组合物。

公开(公告)号：WO1997047758A1

公开(公告)日：1997-12-18

申请号：PCT/US1997009954

申请日：1997-06-06

Applicant: MASSACHUSETTS INSTITUTE OF TECHNOLOGY ,  ALBERT EINSTEIN COLLEGE OF MEDECINE OF YESHIVA UNIVERSITY

Inventor： MASSACHUSETTS INSTITUTE OF TECHNOLOGY ,  ALBERT EINSTEIN COLLEGE OF MEDECINE OF YESHIVA UNIVERSITY ,  LEBOULCH, Philippe ,  BOUHASSIRA, Eric ,  WESTERMAN, Karen ,  TAKEKOSHI, Ken, Julian

IPC: C12N15/86

CPC classification number: C12N15/86 ,  C07K14/805 ,  C12N15/64 ,  C12N15/90 ,  C12N2740/13043

Abstract: Methods and compositions for transforming cells, resulting in efficient and stable site-specific integration of transgenes, are disclosed. Transformation is achieved by introducing into a cell an acceptor vector, preferably a retroviral vector, which integrates into the genome of the cell. The acceptor vector comprises two incompatible lox sequences, L1 and L2. A donor vector is then introduced into the cell comprising a transgene flanked by the same L1 and L2 sequences. Stable gene transfer is initiated by contacting the lox L1 and L2 sequences with Cre recombinase.

Abstract translation: 公开了用于转化细胞，导致转基因的有效和稳定的位点特异性整合的方法和组合物。 通过向细胞中引入整合到细胞基因组中的受体载体，优选逆转录病毒载体来实现转化。 受体载体包含两个不相容的lox序列L1和L2。 然后将供体载体导入包含侧翼具有相同L1和L2序列的转基因的细胞中。 通过将lox L1和L2序列与Cre重组酶接触来启动稳定的基因转移。

公开(公告)号：WO2004054512A2

公开(公告)日：2004-07-01

申请号：PCT/US2003/039526

申请日：2003-12-11

Applicant: GENETIX PHARMACEUTICALS, INC. ,  MASSACHUSETTS INSTITUTE OF TECHNOLOGY ,  LEBOULCH, Philippe ,  PAWLIUK, Robert ,  WESTERMAN, Karen

Inventor： LEBOULCH, Philippe ,  PAWLIUK, Robert ,  WESTERMAN, Karen

IPC: A61K

CPC classification number: A61K48/0058 ,  A01K67/0278 ,  A01K2207/15 ,  A01K2217/00 ,  A01K2227/105 ,  A01K2267/03 ,  A61K38/42 ,  A61K48/00 ,  C07H21/04 ,  C07K14/805 ,  C12N15/63 ,  C12N15/8509 ,  C12N15/86 ,  C12N15/867 ,  C12N2510/00 ,  C12N2740/15043 ,  C12N2740/16011 ,  C12N2740/16043 ,  C12N2830/008 ,  C12N2830/40

Abstract: Retroviral gene therapy vectors that are optimized for erythroid specific expression and treatment of hemoglobinopathic conditions are disclosed.

Abstract translation: 公开了针对红血球特异性表达和血红蛋白病症状治疗优化的逆转录病毒基因治疗载体。

公开(公告)号：WO1994029470A1

公开(公告)日：1994-12-22

申请号：PCT/US1994006661

申请日：1994-06-10

Applicant: MASSACHUSETTS INSTITUTE OF TECHNOLOGY

Inventor： MASSACHUSETTS INSTITUTE OF TECHNOLOGY ,  LEBOULCH, Philippe ,  LONDON, Irving, M. ,  TUAN, Dorothy

IPC: C12N15/85

CPC classification number: C12N15/86 ,  A61K38/00 ,  C07K14/805 ,  C12N15/85 ,  C12N2740/13043 ,  C12N2830/008 ,  C12N2830/42 ,  C12N2830/50 ,  C12N2830/85

Abstract: A process and means for the design and the optimization of retroviral vectors transducing human beta -globin gene and beta -Locus Control Region ( beta -LCR) derivatives, hereafter referred to as [ beta -globin/LCR] retroviruses, which successfully meet the following criteria required for gene therapy applications: (1) stability of proviral transmission (low frequency of rearrangements similar to retroviral vectors considered stable in the art) upon infection of cell-lines and murine bone marrow cells, (2) improved viral titer, thereby allowing successful infection of bone marrow cells, and (3) high erythroid expression of the transduced human beta -globin gene, are described, along with specific constructs.

Abstract translation: 用于设计和优化逆转录病毒载体转导人β-球蛋白基因和β-聚焦对照区（β-LCR）衍生物，以下称为[β-球蛋白/ LCR]逆转录病毒，其成功地满足以下条件 基因治疗应用所需的标准：（1）感染细胞系和鼠骨髓细胞时，病毒传播（与本领域中认为稳定的逆转录病毒载体相似的低频重排）的稳定性，（2）改善的病毒滴度，从而允许 成功感染骨髓细胞，和（3）转导的人β-珠蛋白基因的高红细胞表达，以及具体构建体。

公开(公告)号：EP0706575A1

公开(公告)日：1996-04-17

申请号：EP94920181.0

申请日：1994-06-10

Applicant: MASSACHUSETTS INSTITUTE OF TECHNOLOGY

Inventor： LEBOULCH, Philippe ,  LONDON, Irving, M. ,  TUAN, Dorothy

IPC: C12N15 ,  A61K31 ,  A61K35 ,  A61K38 ,  A61K48 ,  C07K14 ,  C12N5

CPC classification number: C12N15/86 ,  A61K38/00 ,  C07K14/805 ,  C12N15/85 ,  C12N2740/13043 ,  C12N2830/008 ,  C12N2830/42 ,  C12N2830/50 ,  C12N2830/85

Abstract: A process and means for the design and the optimization of retroviral vectors transducing human β-globin gene and β-Locus Control Region (β-LCR) derivatives, hereafter referred to as [β-globin/LCR] retroviruses, which successfully meet the following criteria required for gene therapy applications: (1) stability of proviral transmission (low frequency of rearrangements similar to retroviral vectors considered stable in the art) upon infection of cell-lines and murine bone marrow cells, (2) improved viral titer, thereby allowing successful infection of bone marrow cells, and (3) high erythroid expression of the transduced human β-globin gene, are described, along with specific constructs.

公开(公告)号：EP0914457B1

公开(公告)日：2008-08-13

申请号：EP97928910.5

申请日：1997-06-06

Applicant: MASSACHUSETTS INSTITUTE OF TECHNOLOGY ,  ALBERT EINSTEIN COLLEGE OF MEDICINE OF YESHIVA UNIVERSITY

Inventor： LEBOULCH, Philippe ,  BOUHASSIRA, Eric ,  WESTERMAN, Karen ,  TAKEKOSHI, Ken Julian

IPC: C12N15/86 ,  C12N15/90 ,  C12N15/12 ,  C07K14/805

CPC classification number: C12N15/86 ,  C07K14/805 ,  C12N15/64 ,  C12N15/90 ,  C12N2740/13043

公开(公告)号：EP0783575A1

公开(公告)日：1997-07-16

申请号：EP95932544.0

申请日：1995-09-19

Applicant: MASSACHUSETTS INSTITUTE OF TECHNOLOGY

Inventor： LEBOULCH, Philippe ,  LONDON, Irving, M.

IPC: C12N15 ,  A61K35 ,  A61K38 ,  A61K48 ,  A61P7 ,  C07K14 ,  C12N5 ,  C12P21

CPC classification number: C07K14/805 ,  A01K2217/05 ,  A61K38/00 ,  C12N2799/027

Abstract: Gene therapy methods and compositions for high level expression of anti-sickling beta-globin proteins in erythroid cells for treating Sickle Cell Disease are described.

公开(公告)号：EP1581056B1

公开(公告)日：2010-07-21

申请号：EP03813391.4

申请日：2003-12-11

Applicant: Genetix Pharmaceuticals Inc. ,  MASSACHUSETTS INSTITUTE OF TECHNOLOGY

Inventor： LEBOULCH, Philippe ,  PAWLIUK, Robert ,  WESTERMAN, Karen

IPC: A01N63/00 ,  C07H21/04 ,  C12N15/00 ,  C12N15/867

CPC classification number: A61K48/0058 ,  A01K67/0278 ,  A01K2207/15 ,  A01K2217/00 ,  A01K2227/105 ,  A01K2267/03 ,  A61K38/42 ,  A61K48/00 ,  C07H21/04 ,  C07K14/805 ,  C12N15/63 ,  C12N15/8509 ,  C12N15/86 ,  C12N15/867 ,  C12N2510/00 ,  C12N2740/15043 ,  C12N2740/16011 ,  C12N2740/16043 ,  C12N2830/008 ,  C12N2830/40

Abstract: The invention provides improved compositions and methods for achieving gene therapy in hematopoietic cells and hematopoietic precursor cells, including erythrocytes, erythroid progenitors, and embryonic stem cells. The invention further provides improved gene therapy methods for treating hematopoietic-related disorders. Retroviral gene therapy vectors that are optimized for erythroid specific expression and treatment of hemoglobinopathic conditions are disclosed.

公开(公告)号：EP0706575B1

公开(公告)日：2004-09-22

申请号：EP94920181.8

申请日：1994-06-10

Applicant: MASSACHUSETTS INSTITUTE OF TECHNOLOGY

Inventor： LEBOULCH, Philippe ,  LONDON, Irving, M. ,  TUAN, Dorothy

IPC: C12N15/85 ,  C12N15/86 ,  C07K14/805 ,  A61K48/00 ,  C12N15/12

CPC classification number: C12N15/86 ,  A61K38/00 ,  C07K14/805 ,  C12N15/85 ,  C12N2740/13043 ,  C12N2830/008 ,  C12N2830/42 ,  C12N2830/50 ,  C12N2830/85

公开(公告)号：EP1581056A2

公开(公告)日：2005-10-05

申请号：EP03813391.4

申请日：2003-12-11

Applicant: Genetix Pharmaceuticals Inc. ,  MASSACHUSETTS INSTITUTE OF TECHNOLOGY

Inventor： LEBOULCH, Philippe ,  PAWLIUK, Robert ,  WESTERMAN, Karen

IPC: A01N63/00 ,  C07H21/04 ,  C12N15/00

CPC classification number: A61K48/0058 ,  A01K67/0278 ,  A01K2207/15 ,  A01K2217/00 ,  A01K2227/105 ,  A01K2267/03 ,  A61K38/42 ,  A61K48/00 ,  C07H21/04 ,  C07K14/805 ,  C12N15/63 ,  C12N15/8509 ,  C12N15/86 ,  C12N15/867 ,  C12N2510/00 ,  C12N2740/15043 ,  C12N2740/16011 ,  C12N2740/16043 ,  C12N2830/008 ,  C12N2830/40

Abstract: The invention provides improved compositions and methods for achieving gene therapy in hematopoietic cells and hematopoietic precursor cells, including erythrocytes, erythroid progenitors, and embryonic stem cells. The invention further provides improved gene therapy methods for treating hematopoietic-related disorders. Retroviral gene therapy vectors that are optimized for erythroid specific expression and treatment of hemoglobinopathic conditions are disclosed.