公开(公告)号：US20110136227A1

公开(公告)日：2011-06-09

申请号：US12918460

申请日：2009-02-19

申请人： Andrew Christian Bakker ,  Wilhelmus Theodorus Johannes Maria Christiaan Hermens ,  Yvet Noordman

发明人： Andrew Christian Bakker ,  Wilhelmus Theodorus Johannes Maria Christiaan Hermens ,  Yvet Noordman

IPC分类号： C12N7/00 ,  C12N15/85 ,  C12N5/10

CPC分类号： C12N15/86 ,  C07K14/005 ,  C12N7/00 ,  C12N2710/14143 ,  C12N2750/14122 ,  C12N2750/14243 ,  C12N2800/105 ,  C12N2800/50

摘要： The present invention relates to the improved production of recombinant parvoviral virions in insect cells. In particular, the invention relates to an improved process for the production of recombinant parvoviral virions in insect cells, wherein the full/empty parvoviral virion ratio is increased. The invention also relates to the production of parvoviral vectors that may be used in gene therapy and to improvements in expression of the viral Rep proteins that increase the productivity of parvoviral vectors.

摘要翻译： 本发明涉及在昆虫细胞中改良重组细小病毒病毒粒子的产生。 特别地，本发明涉及在昆虫细胞中生产重组细小病毒病毒粒子的改进方法，其中全部/空白细小病毒病毒粒子比率增加。 本发明还涉及可用于基因治疗的细小病毒载体的生产和提高细小病毒载体生产力的病毒Rep蛋白的表达的改进。

公开(公告)号：US09228174B2

公开(公告)日：2016-01-05

申请号：US13583920

申请日：2011-03-11

申请人： Yvet Noordman ,  Jacek Lubelski ,  Andrew Christian Bakker

发明人： Yvet Noordman ,  Jacek Lubelski ,  Andrew Christian Bakker

IPC分类号： C12N15/35 ,  C12N5/10 ,  C12N7/02 ,  C12N15/85 ,  C12N7/00 ,  C12N15/86

CPC分类号： C12N7/00 ,  C07K14/005 ,  C12N15/86 ,  C12N2710/14143 ,  C12N2750/14143 ,  C12N2750/14151 ,  C12N2750/14152 ,  C12N2800/105 ,  C12N2800/50 ,  C12N2800/90 ,  C12N2820/00

摘要： Nucleic acids encoding Parvoviral Rep proteins with a mutated nuclear localization signal (NLS) are provided. Also provided is a nucleic acid comprising a nucleotide sequence encoding a Parvoviral Rep protein with a mutated zinc finger domain and a nucleic acid comprising a nucleotide sequence encoding a Parvoviral Rep protein comprising an amino acid mutation at position 43, 57, 79, 97, 120, 179, 305, 484, 493 or 571 with reference to SEQ ID NO: 2. Nucleic acid constructs and cells, such as insect cells, comprising the nucleic acids are provided as well as a method for producing a recombinant Parvoviral virion using the nucleic acids.

摘要翻译： 提供了编码具有突变核定位信号（NLS）的细小病毒Rep蛋白的核酸。 还提供了包含编码具有突变的锌指结构域的细小病毒Rep蛋白的核苷酸序列的核酸和包含编码包含第43,57,79,97,120的氨基酸突变的细小病毒Rep蛋白的核苷酸序列的核酸 ，179,305,448,493或571，参考SEQ ID NO：2.提供了核酸构建体和包含核酸的细胞，例如昆虫细胞，以及使用核酸产生重组细小病毒病毒体的方法 酸。

公开(公告)号：US20110119777A1

公开(公告)日：2011-05-19

申请号：US12679144

申请日：2008-09-18

申请人： Wilhelmus Theodorus Johannes Maria Christiaan Hermens ,  Yvet Noordman ,  Andrew Christian Bakker

发明人： Wilhelmus Theodorus Johannes Maria Christiaan Hermens ,  Yvet Noordman ,  Andrew Christian Bakker

IPC分类号： A01K67/033 ,  C12P21/00 ,  C12P19/34 ,  C12N5/10 ,  A01H5/00

CPC分类号： C12N15/86 ,  A01K2217/05 ,  C12N2710/14143 ,  C12N2830/00

摘要： The present invention provides a method for enhanced production of a gene product of interest in a cell, using the AAV replication machinery. The present invention further relates to a cell for use in the method of the invention and a non-human transgenic animal or a transgenic plant comprising a cell of the invention.

摘要翻译： 本发明提供使用AAV复制机制增强细胞中感兴趣的基因产物的产生的方法。 本发明还涉及用于本发明方法的细胞和非人转基因动物或包含本发明细胞的转基因植物。

公开(公告)号：US08642314B2

公开(公告)日：2014-02-04

申请号：US12918460

申请日：2009-02-19

申请人： Andrew Christian Bakker ,  Wilhelmus Theodorus Johannes Maria Christiaan Hermens ,  Yvet Noordman

发明人： Andrew Christian Bakker ,  Wilhelmus Theodorus Johannes Maria Christiaan Hermens ,  Yvet Noordman

IPC分类号： C12N7/00 ,  C12N7/01

CPC分类号： C12N15/86 ,  C07K14/005 ,  C12N7/00 ,  C12N2710/14143 ,  C12N2750/14122 ,  C12N2750/14243 ,  C12N2800/105 ,  C12N2800/50

摘要： The present invention relates to the improved production of recombinant parvoviral virions in insect cells. In particular, the invention relates to an improved process for the production of recombinant parvoviral virions in insect cells, wherein the full/empty parvoviral virion ratio is increased. The invention also relates to the production of parvoviral vectors that may be used in gene therapy and to improvements in expression of the viral Rep proteins that increase the productivity of parvoviral vectors.

摘要翻译： 本发明涉及在昆虫细胞中改良重组细小病毒病毒粒子的产生。 特别地，本发明涉及在昆虫细胞中生产重组细小病毒病毒粒子的改进方法，其中全部/空白细小病毒病毒粒子比率增加。 本发明还涉及可用于基因治疗的细小病毒载体的生产和提高细小病毒载体生产力的病毒Rep蛋白的表达的改进。

公开(公告)号：US09115373B2

公开(公告)日：2015-08-25

申请号：US12679144

申请日：2008-09-18

申请人： Wilhelmus Theodorus Johannes Maria Christiaan Hermens ,  Yvet Noordman ,  Andrew Christian Bakker

发明人： Wilhelmus Theodorus Johannes Maria Christiaan Hermens ,  Yvet Noordman ,  Andrew Christian Bakker

IPC分类号： C12P21/06 ,  C12N5/07 ,  C12N15/86

CPC分类号： C12N15/86 ,  A01K2217/05 ,  C12N2710/14143 ,  C12N2830/00

摘要： The present invention provides a method for enhanced production of a gene product of interest in a cell, using the AAV replication machinery. The present invention further relates to a cell for use in the method of the invention and a non-human transgenic animal or a transgenic plant comprising a cell of the invention.

摘要翻译： 本发明提供使用AAV复制机制增强细胞中感兴趣的基因产物的产生的方法。 本发明还涉及用于本发明方法的细胞和非人转基因动物或包含本发明细胞的转基因植物。

公开(公告)号：US20130023034A1

公开(公告)日：2013-01-24

申请号：US13583920

申请日：2011-03-11

申请人： Yvet Noordman ,  Jacek Lubelski ,  Andrew Christian Bakker

发明人： Yvet Noordman ,  Jacek Lubelski ,  Andrew Christian Bakker

IPC分类号： C12N15/35 ,  C12N5/10 ,  C12N7/02 ,  C12N15/85

CPC分类号： C12N7/00 ,  C07K14/005 ,  C12N15/86 ,  C12N2710/14143 ,  C12N2750/14143 ,  C12N2750/14151 ,  C12N2750/14152 ,  C12N2800/105 ,  C12N2800/50 ,  C12N2800/90 ,  C12N2820/00

摘要： The invention relates to a nucleic acid comprising a nucleotide sequence encoding a Parvoviral Rep protein, wherein a nuclear localization signal (NLS) in said Parvoviral Rep protein is mutated as compared with a corresponding wild type sequence. The invention also relates to a nucleic acid comprising a nucleotide sequence encoding a Parvoviral Rep protein, wherein the zinc finger domain in said Parvoviral Rep protein is mutated as compared with a corresponding wild type sequence. Further, the invention relates to a nucleic acid comprising a nucleotide sequence encoding a Parvoviral Rep protein, wherein an amino acid at position 43, 57, 79, 97, 120, 179, 305, 484, 493 or 571 of the said Parvoviral Rep protein is mutated in comparison to a corresponding wild type sequence, said amino acid position being defined with reference to SEQ ID NO: 2.

摘要翻译： 本发明涉及包含编码细小病毒Rep蛋白的核苷酸序列的核酸，其中所述细小病毒Rep蛋白中的核定位信号（NLS）与相应的野生型序列相比是突变的。 本发明还涉及包含编码细小病毒Rep蛋白的核苷酸序列的核酸，其中所述细小病毒Rep蛋白中的锌指结构域与相应的野生型序列相比是突变的。 此外，本发明涉及包含编码细小病毒Rep蛋白的核苷酸序列的核酸，其中所述细小病毒Rep蛋白的43,57,79,97,120,179,305,484,493或571位的氨基酸 与相应的野生型序列相比突变，所述氨基酸位置参照SEQ ID NO：2定义。