公开(公告)号：US11701435B2

公开(公告)日：2023-07-18

申请号：US16820066

申请日：2020-03-16

申请人： bluebird bio, Inc. ,  Massachusetts Institute of Technology

发明人： Philippe Louis Leboulch ,  Robert Pawliuk ,  Karen Westerman

IPC分类号： A01N63/00 ,  C12N15/79 ,  C07H21/04 ,  A61K48/00 ,  C07K14/805 ,  A01K67/027 ,  C12N15/85 ,  C12N15/86 ,  A61K38/42 ,  C12N15/867 ,  C12N15/63

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

摘要： Provided are improved compositions and methods for achieving gene therapy in hematopoietic cells and hematopoietic precursor cells, including erythrocytes, erythroid progenitors, and embryonic stem cells. Also provided are 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：US20170145388A1

公开(公告)日：2017-05-25

申请号：US15356830

申请日：2016-11-21

申请人： GLAXOSMITHKLINE INTELLECTUAL PROPERTY DEVELOPMENT LIMITED

发明人： Sabine JOHNSON ,  Celeste PALLANT ,  Eirini VAMVA ,  Conrad VINK

IPC分类号： C12N7/00 ,  C12N15/86

CPC分类号： C12N7/00 ,  C12N5/10 ,  C12N7/025 ,  C12N7/045 ,  C12N15/85 ,  C12N15/86 ,  C12N2740/15043 ,  C12N2740/16043 ,  C12N2740/16052 ,  C12N2830/006 ,  C12N2830/40 ,  C12N2830/60

摘要： The invention relates to retroviral producer cell comprising nucleic acid sequences encoding: gag and pol proteins; envelope protein or a functional substitute thereof; and the RNA genome of the retroviral vector particle, wherein said nucleic acid sequences are all located at a single locus within the retroviral producer cell genome.

公开(公告)号：US20170101647A1

公开(公告)日：2017-04-13

申请号：US15287622

申请日：2016-10-06

申请人： DNA2.0, INC.

发明人： Jeremy Minshull ,  Mark Welch ,  Sridhar Govindrajan ,  Maggie Lee ,  Kate Caves ,  Jon Ness

IPC分类号： C12N15/67 ,  C12N9/12 ,  C12N15/85 ,  C12N15/52 ,  C12N15/81

CPC分类号： C12N15/67 ,  C12N9/12 ,  C12N9/1241 ,  C12N15/1082 ,  C12N15/52 ,  C12N15/625 ,  C12N15/63 ,  C12N15/81 ,  C12N15/815 ,  C12N15/85 ,  C12N15/90 ,  C12N2830/007 ,  C12N2830/40 ,  C12N2830/42 ,  C12N2840/203 ,  C12R1/84 ,  C12R1/865 ,  C12Y207/00

摘要： The present invention provides polynucleotide vectors for high expression of heterologous genes. Some vectors further comprise novel transposons and transposases that further improve expression. Further disclosed are vectors that can be used in a gene transfer system for stably introducing nucleic acids into the DNA of a cell. The gene transfer systems can be used in methods, for example, gene expression, bioprocessing, gene therapy, insertional mutagenesis, or gene discovery.

公开(公告)号：US20170101630A1

公开(公告)日：2017-04-13

申请号：US15287660

申请日：2016-10-06

申请人： DNA2.0, INC.

发明人： Jeremy Minshull ,  Mark Welch ,  Sridhar Govindrajan ,  Maggie Lee ,  Kate Caves ,  Jon Ness

IPC分类号： C12N9/12 ,  C12N15/81 ,  C12N15/85

CPC分类号： C12N15/67 ,  C12N9/12 ,  C12N9/1241 ,  C12N15/1082 ,  C12N15/52 ,  C12N15/625 ,  C12N15/63 ,  C12N15/81 ,  C12N15/815 ,  C12N15/85 ,  C12N15/90 ,  C12N2830/007 ,  C12N2830/40 ,  C12N2830/42 ,  C12N2840/203 ,  C12R1/84 ,  C12R1/865 ,  C12Y207/00

摘要： The present invention provides polynucleotide vectors for high expression of heterologous genes. Some vectors further comprise novel transposons and transposases that further improve expression. Further disclosed are vectors that can be used in a gene transfer system for stably introducing nucleic acids into the DNA of a cell. The gene transfer systems can be used in methods, for example, gene expression, bioprocessing, gene therapy, insertional mutagenesis, or gene discovery.

公开(公告)号：US09339519B2

公开(公告)日：2016-05-17

申请号：US12857514

申请日：2010-08-16

申请人： David Ayares

发明人： David Ayares

IPC分类号： A01K67/00 ,  A01K67/033 ,  A61K35/39 ,  A01K67/027 ,  C12N15/85

CPC分类号： A01K67/0276 ,  A01K67/0278 ,  A01K2217/052 ,  A01K2217/075 ,  A01K2217/15 ,  A01K2217/206 ,  A01K2227/105 ,  A01K2227/108 ,  A01K2267/025 ,  A01K2267/0362 ,  A61K35/39 ,  C12N9/1051 ,  C12N15/8509 ,  C12N2830/40 ,  C12Y204/01087

摘要： The present invention provides certain animals, and in particular porcine animals, tissue and cells derived from these, which lack any expression of functional alpha 1,3 galactosyltransferase (αGT) and express one or more additional transgenes which make them suitable donors for pancreatic islet xenotransplantation. Methods of treatment and prevention of diabetes using cells derived from such animals are also provided.

摘要翻译： 本发明提供某些动物，特别是猪动物，衍生自其的动物组织和细胞，其缺乏功能性α1,3半乳糖基转移酶（αGT）的任何表达，并表达一种或多种另外的转基因，使其成为胰岛异种移植的合适供体 。 还提供了使用源自这些动物的细胞治疗和预防糖尿病的方法。

公开(公告)号：US20150291976A1

公开(公告)日：2015-10-15

申请号：US14683121

申请日：2015-04-09

申请人： DNA2.0, INC.

发明人： Jeremy Minshull ,  Mark Welch ,  Sridhar Govindrajan ,  Kate Caves

IPC分类号： C12N15/85 ,  C07K16/00 ,  C12N9/12

CPC分类号： C12N9/1241 ,  A61K31/00 ,  A61K31/7105 ,  A61K38/00 ,  C07K2/00 ,  C07K14/43586 ,  C07K14/463 ,  C07K16/00 ,  C07K16/32 ,  C07K2317/10 ,  C07K2317/24 ,  C07K2317/56 ,  C07K2319/09 ,  C07K2319/80 ,  C12N15/85 ,  C12N15/907 ,  C12N2800/90 ,  C12N2830/40 ,  C12N2830/60 ,  C12Y207/07

摘要： The present invention provides polynucleotide vectors for high expression of heterologous genes, and methods for constructing such vectors. Some vectors further comprise novel transposons and transposases that further improve expression. Further disclosed are vectors that can be used in a gene transfer system for stably introducing nucleic acids into the DNA of a cell. The gene transfer systems can be used in methods, for example, but not limited to, gene expression, gene therapy, insertional mutagenesis, or gene discovery.

公开(公告)号：US08980627B2

公开(公告)日：2015-03-17

申请号：US12515584

申请日：2007-11-21

申请人： Takashi Kondo

发明人： Takashi Kondo

IPC分类号： C12N15/00 ,  C12N5/00 ,  C12N5/02 ,  C12P21/06 ,  C07H21/04 ,  A01K67/027 ,  C07K14/47 ,  C12N15/85

CPC分类号： A01K67/0275 ,  A01K2217/052 ,  A01K2217/072 ,  A01K2227/105 ,  A01K2267/03 ,  A01K2267/0393 ,  C07K14/4705 ,  C12N15/8509 ,  C12N2830/40

摘要： This invention relates to a method for stably expressing a transgene integrated into the genome of an animal cell or of an animal over a long period. Specifically, this invention provides: an approximately 2.5 kb XhoI-BamHI fragment (or XB fragment) derived from the Evx2-Hoxd13 intergenic region of the animal genome, or a homologue thereof; a DNA containing a foreign DNA wherein the DNA has been inserted between the two essentially identical XB fragments or homologues thereof; a vector, animal cell, or nonhuman mammalian animal containing said DNA; and use of the vector, animal cell, or nonhuman mammalian animal for production of a substance or therapy.

摘要翻译： 本发明涉及一种长期稳定表达整合到动物细胞或动物基因组中的转基因的方法。 具体地说，本发明提供：衍生自动物基因组的Evx2-Hoxd13基因间区的约2.5kb XhoI-BamHI片段（或XB片段）或其同源物; 含有外源DNA的DNA，其中DNA已经插入在两个基本相同的XB片段或其同源物之间; 含有所述DNA的载体，动物细胞或非人哺乳动物; 以及使用载体，动物细胞或非人哺乳动物来生产物质或治疗。

公开(公告)号：US20120316225A1

公开(公告)日：2012-12-13

申请号：US13505823

申请日：2010-11-08

申请人： Mary B. Breslin ,  Michael S. Lan

发明人： Mary B. Breslin ,  Michael S. Lan

IPC分类号： A61K31/7088 ,  A61P35/00 ,  G01N21/76 ,  C12N15/85 ,  C12N15/861

CPC分类号： C12N15/86 ,  C07K14/005 ,  C07K2319/55 ,  C07K2319/61 ,  C12N15/85 ,  C12N2710/10343 ,  C12N2710/16622 ,  C12N2710/16634 ,  C12N2830/008 ,  C12N2830/32 ,  C12N2830/40

摘要： A modification of the existing INSM1 promoter region has been discovered that incorporated DNA elements that silence expression of neuronal genes in non-neuronal cells and that has increased the effectiveness and safety of using the INSM1 promoter for tumor treatment. One modification was addition of one or two tandem copies of neuronal restrictive silencer elements (NRSEs) derived either from the mouse nicotinic acetylcholine receptor (nAChR) or the rat superior cervical ganglion 10 (SCG10) promoters. These NRSEs were placed in the expression construct either directly upstream or downstream of the INSM1 promoter sequence. The most effective expression construct was the nAChR NRSE element positioned downstream of the INSM1 promoter. This expression construct increased the tissue specificity of the INSM1 promoter without a significant decrease in its activity. In addition, the modified INSM1 promoter was placed into a viral vector, adenovirus 5. Constructs with an insulator element, the chicken HS4 β-globin insulator element, with the INSM1 promoter was shown to decrease the interference of the viral genome on its expression. Constructs have been made that do not decrease the INSM1 promoter activity but significantly augment the tumor specificity of the promoter. Linking the construct to a reporter gene allowed for detection of the placement of the viral vector, and this detection can be used for diagnosing or locating neuroendocrine tumors.

摘要翻译： 已经发现现有的INSM1启动子区域的修饰是掺入了在非神经元细胞中沉默神经元基因表达的DNA元件，并增加了使用INSM1启动子进行肿瘤治疗的有效性和安全性。 一个修改是从小鼠烟碱乙酰胆碱受体（nAChR）或大鼠上颈部神经节10（SCG10）启动子衍生的神经元限制性消音元件（NRSE）的一个或两个串联拷贝的添加。 将这些NRSEs直接置于INSM1启动子序列的上游或下游的表达构建体中。 最有效的表达构建体是位于INSM1启动子下游的nAChR NRSE元件。 该表达构建体增加了INSM1启动子的组织特异性，而其活性没有显着降低。 此外，将修饰的INSM1启动子置于病毒载体，腺病毒5中。具有绝缘体元件，具有INSM1启动子的鸡HS4和bgr - 球蛋白绝缘子元件的构建体显示可减少病毒基因组对其表达的干扰 。 已经建立了不降低INSM1启动子活性但显着增加启动子的肿瘤特异性的构建体。 将构建体连接到允许检测病毒载体的位置的报告基因，并且该检测可用于诊断或定位神经内分泌肿瘤。

公开(公告)号：US20110038841A1

公开(公告)日：2011-02-17

申请号：US12857514

申请日：2010-08-16

申请人： David Ayares

发明人： David Ayares

IPC分类号： A61K35/39 ,  A01K67/027 ,  C12N5/10 ,  A61P3/10

CPC分类号： A01K67/0276 ,  A01K67/0278 ,  A01K2217/052 ,  A01K2217/075 ,  A01K2217/15 ,  A01K2217/206 ,  A01K2227/105 ,  A01K2227/108 ,  A01K2267/025 ,  A01K2267/0362 ,  A61K35/39 ,  C12N9/1051 ,  C12N15/8509 ,  C12N2830/40 ,  C12Y204/01087

摘要： The present invention provides certain animals, and in particular porcine animals, tissue and cells derived from these, which lack any expression of functional alpha 1,3 galactosyltransferase (αGT) and express one or more additional transgenes which make them suitable donors for pancreatic islet xenotransplantation. Methods of treatment and prevention of diabetes using cells derived from such animals are also provided.

摘要翻译： 本发明提供某些动物，特别是猪动物，衍生自其的动物组织和细胞，其缺乏功能性α1,3半乳糖基转移酶（αGT）的任何表达，并表达一种或多种另外的转基因，使其成为胰岛异种移植的合适供体 。 还提供了使用源自这些动物的细胞治疗和预防糖尿病的方法。

公开(公告)号：US20100330675A1

公开(公告)日：2010-12-30

申请号：US12671586

申请日：2008-07-30

申请人： Frederique Magdinier ,  Eric Gilson ,  Alexandre Ottaviani ,  Sylvie Gervier Rival

发明人： Frederique Magdinier ,  Eric Gilson ,  Alexandre Ottaviani ,  Sylvie Gervier Rival

IPC分类号： C12N15/79 ,  C07H21/04 ,  C12N5/071

CPC分类号： C12N15/85 ,  C12N2830/40

摘要： Polynucleotides with insulating properties allowing protection of the expression of a transgene from adjacent cis elements in higher eukaryotic cells. In particular, these polynucleotides can be used for transgenesis, gene therapy and the production of recombinant proteins.

摘要翻译： 具有绝缘性质的多核苷酸，可保护高等真核细胞中相邻顺式元件的转基因表达。 特别地，这些多核苷酸可用于转基因，基因治疗和重组蛋白的产生。