公开(公告)号：US20060024274A1

公开(公告)日：2006-02-02

申请号：US11154421

申请日：2005-06-15

Applicant: Alan Kingsman ,  Miles Carroll ,  Jonathan Rohll ,  Kyriacos Mitrophanous ,  Narry Kim

Inventor： Alan Kingsman ,  Miles Carroll ,  Jonathan Rohll ,  Kyriacos Mitrophanous ,  Narry Kim

IPC: A61K48/00 ,  C12N15/867

CPC classification number: C12N15/86 ,  A61K48/00 ,  C12N7/00 ,  C12N2710/24143 ,  C12N2710/24144 ,  C12N2740/15043 ,  C12N2740/15052 ,  C12N2740/15062 ,  C12N2810/6081

Abstract: A retroviral vector derived from a non-primate lentivirus genome comprising a deleted gag gene wherein the deletion in gag removes one or more nucleotides downstream of nucleotide 350 of the gag coding sequence.

公开(公告)号：US20080269473A1

公开(公告)日：2008-10-30

申请号：US12077802

申请日：2008-03-20

Applicant: Alan John Kingsman ,  Narry Kim ,  Ekaterini Kotsopoulou ,  Jonathan Rohll ,  Kyriacos A. Mitrophanous

Inventor： Alan John Kingsman ,  Narry Kim ,  Ekaterini Kotsopoulou ,  Jonathan Rohll ,  Kyriacos A. Mitrophanous

IPC: C07H21/00

CPC classification number: C12N7/00 ,  A61K48/00 ,  C07K14/005 ,  C12N15/86 ,  C12N2740/15022 ,  C12N2740/15043 ,  C12N2740/15052 ,  C12N2740/16043 ,  C12N2740/16122 ,  C12N2800/22 ,  C12N2830/50

Abstract: A method of producing a replication defective retrovirus comprising transfecting a producer cell with the following: iii) a retroviral genome; iv) a nucleotide sequence coding for retroviral gag and pol proteins; and iii) nucleotide sequences encoding other essential viral packaging components not encoded by the nucleotide sequence of (ii); characterised in that the nucleotide sequence coding for retroviral gag and pol proteins is codon optimised for expression in the producer cell.

Abstract translation: 一种产生复制缺陷型逆转录病毒的方法，包括用以下转染生产细胞：iii）逆转录病毒基因组; iv）编码逆转录病毒gag和pol蛋白的核苷酸序列; 和iii）编码不由（ii）的核苷酸序列编码的其它基本病毒包装组分的核苷酸序列; 其特征在于编码逆转录病毒gag和pol蛋白的核苷酸序列被密码子优化用于在生产细胞中表达。

公开(公告)号：US20100273996A1

公开(公告)日：2010-10-28

申请号：US12587236

申请日：2009-10-02

Applicant: Alan John Kingsman ,  Narry Kim ,  Ekaterini Kotsopoulou ,  Jonathan Rohll ,  Kyriacos A. Mitrophanous

Inventor： Alan John Kingsman ,  Narry Kim ,  Ekaterini Kotsopoulou ,  Jonathan Rohll ,  Kyriacos A. Mitrophanous

IPC: C07H21/04

CPC classification number: C12N7/00 ,  A61K48/00 ,  C07K14/005 ,  C12N15/86 ,  C12N2740/15022 ,  C12N2740/15043 ,  C12N2740/15052 ,  C12N2740/16043 ,  C12N2740/16122 ,  C12N2800/22 ,  C12N2830/50

Abstract: A method of producing a replication defective retrovirus comprising transfecting a producer cell with the following: iii) a retroviral genome; iv) a nucleotide sequence coding for retroviral gag and pot proteins; and iii) nucleotide sequences encoding other essential viral packaging components not encoded by the nucleotide sequence of (ii); characterised in that the nucleotide sequence coding for retroviral gag and pot proteins is codon optimised for expression in the producer cell.

Abstract translation: 一种产生复制缺陷型逆转录病毒的方法，包括用以下转染生产细胞：iii）逆转录病毒基因组; iv）编码逆转录病毒gag和pot蛋白的核苷酸序列; 和iii）编码不由（ii）的核苷酸序列编码的其它基本病毒包装组分的核苷酸序列; 其特征在于编码逆转录病毒gag和pot蛋白的核苷酸序列被密码子优化用于在生产细胞中表达。

公开(公告)号：US20090111106A1

公开(公告)日：2009-04-30

申请号：US12168563

申请日：2008-07-07

Applicant: Kyri Mitrophanous ,  Jonathan Rohll ,  James Miskin ,  Susan Mary Kingsman

Inventor： Kyri Mitrophanous ,  Jonathan Rohll ,  James Miskin ,  Susan Mary Kingsman

IPC: C12Q1/68 ,  C12N15/11 ,  C12N15/00 ,  C12N7/00 ,  C12N5/06 ,  C12N15/87

CPC classification number: C12N15/86 ,  A61K48/00 ,  C12N9/0071 ,  C12N2740/15043 ,  C12N2830/48 ,  C12N2840/206

Abstract: The present invention provides a vector system comprising a mutated post-transcriptional regulatory element. In particular, the present invention relates to a mutated WPRE sequence that can efficiently express nucleotides of interest in a retroviral vector system. The present invention also relates to methods of delivering and expressing nucleotides of interest to a target cell.

Abstract translation: 本发明提供了包含突变后转录调节元件的载体系统。 特别地，本发明涉及能够在逆转录病毒载体系统中有效表达感兴趣的核苷酸的突变的WPRE序列。 本发明还涉及递送和表达靶细胞的目标核苷酸的方法。

公开(公告)号：US07419829B2

公开(公告)日：2008-09-02

申请号：US10873573

申请日：2004-06-21

Applicant: Kyri Mitrophanous ,  Jonathan Rohll ,  James Miskin ,  Susan Marie Kingsman

Inventor： Kyri Mitrophanous ,  Jonathan Rohll ,  James Miskin ,  Susan Marie Kingsman

IPC: C12N15/63 ,  C12N15/64 ,  C12N15/867 ,  C12N5/10 ,  C07H21/04 ,  C07H21/02 ,  A61K48/00 ,  C12Q1/68 ,  C12Q1/70

CPC classification number: C12N15/86 ,  A61K48/00 ,  C12N9/0071 ,  C12N2740/15043 ,  C12N2830/48 ,  C12N2840/206

Abstract: The present invention provides a vector system comprising a mutated post-transcriptional regulatory element. In particular, the present invention relates to a mutated WPRE sequence that can efficiently express nucleotides of interest in a retroviral vector system. The present invention also relates to methods of delivering and expressing nucleotides of interest to a target cell.

Abstract translation: 本发明提供了包含突变后转录调节元件的载体系统。 特别地，本发明涉及能够在逆转录病毒载体系统中有效表达感兴趣的核苷酸的突变的WPRE序列。 本发明还涉及递送和表达靶细胞的目标核苷酸的方法。

公开(公告)号：US07259015B2

公开(公告)日：2007-08-21

申请号：US10408456

申请日：2003-04-07

Applicant: Alan John Kingsman ,  Nicholas D. Mazarakis ,  Enca Martin-Rendon ,  Mimoun Azzouz ,  Jonathan Rohll

Inventor： Alan John Kingsman ,  Nicholas D. Mazarakis ,  Enca Martin-Rendon ,  Mimoun Azzouz ,  Jonathan Rohll

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

CPC classification number: C12N15/86 ,  A61K48/00 ,  C12N9/0071 ,  C12N2740/15043 ,  C12N2830/48 ,  C12N2840/206

Abstract: Provided are retroviral vector genomes and vector systems comprising the genomes. In particular, a retroviral vector genome comprising two or more NOIs, operably linked by one or more Internal Ribosome Entry Site(s); a lentiviral vector genome comprising two or more NOIs suitable for treating a neurodegenerative disorder; and a lentiviral vector genome which encodes tyrosine hydroxylase, GTP-cyclohydrolase I and, optionally, Aromatic Amino Acid Dopa Decarboxylase are provided.

Abstract translation: 提供了包含基因组的逆转录病毒载体基因组和载体系统。 特别地，包含由一个或多个内部核糖体进入位点可操作地连接的两个或更多个NOI的逆转录病毒载体基因组; 包含两种或更多种适用于治疗神经变性疾病的NOI的慢病毒载体基因组; 并提供编码酪氨酸羟化酶，GTP-环化水解酶I和任选的芳香族氨基酸多巴脱羧酶的慢病毒载体基因组。

公开(公告)号：US20050260164A1

公开(公告)日：2005-11-24

申请号：US11102428

申请日：2005-04-08

Applicant: Doug Jolly ,  Jonathan Rohll ,  Bernd Buehler ,  Kyri Mitrophanous ,  Pippa Radcliffe

Inventor： Doug Jolly ,  Jonathan Rohll ,  Bernd Buehler ,  Kyri Mitrophanous ,  Pippa Radcliffe

IPC: A61K48/00 ,  C12N15/63 ,  C12N15/67 ,  C12N15/86 ,  C12N15/867 ,  C12Q1/68

CPC classification number: C12N15/67 ,  C12N15/63 ,  C12N15/86 ,  C12N2740/15043 ,  C12N2830/003 ,  C12N2840/203 ,  C12N2840/445

Abstract: Provided is an improved method for controlling gene expression in vivo through the use of a gene switch comprising one or more aptamer sequences operably linked to or incorporated into the untranslated regions (UTRs) of a transgene or nucleotide sequence of interest. Also provided are expression vectors having aptamer sequences located within the 3′ UTR, the 5′ UTR and between the genes of a multicistronic mRNA, as well as methods of using the expression vectors for controlling or regulating gene expression.

Abstract translation: 本发明提供了一种通过使用包含与目的转基因或核苷酸序列的非翻译区（UTR）可操作连接或并入其中的一个或多个适体序列的基因切换来控制体内基因表达的改进方法。 还提供了具有位于3'UTR，5'UTR内的适配子序列和多顺反子mRNA的基因之间的表达载体，以及使用表达载体来控制或调节基因表达的方法。

公开(公告)号：US20050042234A1

公开(公告)日：2005-02-24

申请号：US10258089

申请日：2001-04-18

Applicant: Alan Kingsman ,  Narry Kim ,  Ekaterini Kotsopoulou ,  Jonathan Rohll ,  Kyriacos Mitrophanous

Inventor： Alan Kingsman ,  Narry Kim ,  Ekaterini Kotsopoulou ,  Jonathan Rohll ,  Kyriacos Mitrophanous

IPC: C12N15/09 ,  A61K35/76 ,  A61K48/00 ,  C07K14/155 ,  C12N5/10 ,  C12N7/00 ,  C12N15/867 ,  A61K39/21

CPC classification number: C12N7/00 ,  A61K48/00 ,  C07K14/005 ,  C12N15/86 ,  C12N2740/15022 ,  C12N2740/15043 ,  C12N2740/15052 ,  C12N2740/16043 ,  C12N2740/16122 ,  C12N2800/22 ,  C12N2830/50

Abstract: Provided herein are methods for producing a replication defective retrovirus, which comprises transfecting a producer cell with (1) a retroviral genome; (2) a nucleotide sequence coding for retroviral gag and pol proteins that is codon-optimized for expression in the producer cell; and (3) nucleotide sequences encoding other essential viral packaging components not encoded by the nucleotide sequence of (1).

Abstract translation: 本文提供了用于产生复制缺陷型逆转录病毒的方法，其包括用（1）逆转录病毒基因组转染生产细胞; （2）编码用于在生产细胞中表达的密码子优化的逆转录病毒gag和pol蛋白质的核苷酸序列; 和（3）编码不由（1）的核苷酸序列编码的其它基本病毒包装组分的核苷酸序列。

公开(公告)号：US20070025970A1

公开(公告)日：2007-02-01

申请号：US11486914

申请日：2006-07-14

Applicant: Alan Kingsman ,  Nicholas Mazarakis ,  Enca Martin-Rendon ,  Mimoun Azzouz ,  Jonathan Rohll

Inventor： Alan Kingsman ,  Nicholas Mazarakis ,  Enca Martin-Rendon ,  Mimoun Azzouz ,  Jonathan Rohll

IPC: A61K48/00 ,  C12N15/867

CPC classification number: C12N15/86 ,  A61K48/00 ,  C12N9/0071 ,  C12N2740/15043 ,  C12N2830/48 ,  C12N2840/206

Abstract: The present invention relates to retroviral vector genomes and to vector systems comprising such genomes. In particular the present invention relates to a retroviral vector genome comprising two or more NOIs operably linked by one or more Internal Ribosome Entry Site(s); a lentiviral vector genome comprising two or more NOIs suitable for treating a neurodegenerative disorder; and a lentiviral vector genome which encodes tyrosine hydroxylase, GTP-cyclohydrolase I and optionally Aromatic Amino Acid Dopa Decarboxylase.

Abstract translation: 本发明涉及逆转录病毒载体基因组以及包含这种基因组的载体系统。 特别地，本发明涉及包含两个或更多个通过一个或多个内部核糖体进入位点可操作地连接的NOI的逆转录病毒载体基因组; 包含两种或更多种适用于治疗神经变性疾病的NOI的慢病毒载体基因组; 和编码酪氨酸羟化酶，GTP-环化水解酶I和任选的芳香族氨基酸多巴脱羧酶的慢病毒载体基因组。

公开(公告)号：US06969598B2

公开(公告)日：2005-11-29

申请号：US10134643

申请日：2002-04-30

Applicant: John C. Olsen ,  Kyriacos Andreou Mitrophanous ,  Jonathan Rohll ,  Alan John Kingsman ,  Fiona Margaret Ellard

Inventor： John C. Olsen ,  Kyriacos Andreou Mitrophanous ,  Jonathan Rohll ,  Alan John Kingsman ,  Fiona Margaret Ellard

IPC: A61K48/00 ,  C07K14/11 ,  C12N5/08 ,  C12N5/10 ,  C12N7/01 ,  C12N7/08 ,  C12N15/867 ,  C12P21/06 ,  C07H21/02 ,  C12N5/00 ,  C12N15/00 ,  C12Q1/70

CPC classification number: C12N7/00 ,  A61K48/00 ,  C12N15/86 ,  C12N2740/15043 ,  C12N2740/15052 ,  C12N2740/15061 ,  C12N2740/15064 ,  C12N2740/16134 ,  C12N2800/22 ,  C12N2830/002 ,  C12N2830/003 ,  C12N2830/48

Abstract: A method for producing viral vectors is described using packaging and producer cell lines is described. The producer cell comprises: (i) a first nucleotide sequence (NS) encoding a toxic viral envelope protein operably linked to a promoter; wherein the promoter is operably linked to at least one copy of a TRE; (ii) a second NS wherein the second NS comprises a sequence encoding a tetracycline modulator; (iii) a third NS encoding a retrovirus nucleocapsid protein; and (iv) a fourth NS comprising a retroviral sequence capable of being encapsidated in the nucleocapsid protein such that the retroviral vector particle titre obtainable from the producer cell is regulatable by tetracycline and an initial stimulus with sodium butyrate or functional analogues thereof.

Abstract translation: 使用包装描述生产病毒载体的方法，描述生产细胞系。 生产细胞包括：（i）编码与启动子可操作地连接的毒性病毒包膜蛋白的第一核苷酸序列（NS） 其中所述启动子可操作地连接至TRE的至少一个拷贝; （ii）第二NS，其中所述第二NS包含编码四环素调节剂的序列; （iii）编码逆转录病毒核衣壳蛋白的第三NS; 和（iv）第四NS，其包含能够被包裹在核壳蛋白中的逆转录病毒序列，使得可从生殖细胞获得的逆转录病毒载体颗粒滴度由四环素调节，并且用丁酸钠或其功能类似物进行初始刺激。