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1. 发明申请

WO9429442A3 TIGHT CONTROL OF GENE EXPRESSION IN EUCARYOTIC CELLS BY TETRACYCLINE-RESPONSIVE PROMOTERS 审中-公开
标题翻译：通过四环素反应促进剂对真核细胞中基因表达的严格控制
公开(公告)号：WO9429442A3
公开(公告)日：1995-02-02
申请号：PCT/US9406734
申请日：1994-06-14
申请人： BASF AG , BUJARD HERMANN , GOSSEN MANFRED , SALFELD JOCHEN G , VOSS JEFFREY W
发明人： BUJARD HERMANN , GOSSEN MANFRED , SALFELD JOCHEN G , VOSS JEFFREY W
IPC分类号： A01K67/027 , A61K48/00 , C07K14/00 , C12N5/08 , C12N5/10 , C12N15/00 , C12N15/09 , C12N15/31 , C12N15/62 , C12N15/63 , C12N15/85 , C12R1/91 , C12N1/15 , C12N1/19 , C12N15/12 , C12N15/90
CPC分类号： A01K67/0275 , A01K2217/05 , A01K2217/075 , C07K2319/09 , C07K2319/61 , C07K2319/71 , C07K2319/80 , C12N15/62 , C12N15/635 , C12N15/85 , C12N2830/006
摘要： Transgenic animals carrying two transgenes, the first coding for a transactivator fusion protein comprising a tet repressor and a polypeptide which directly or indirectly activates in eucaryotic cells, and the second comprising a gene operably linked to a minimal promotor operably linked to at least one tet operator sequence, are disclosed. Isolated DNA molecules (e.g., targeting vectors) for integrating a polynucleotide sequence encoding a transactivator of the invention at a predetermined location within a second target DNA molecule by homologous recombination are also disclosed. Transgenic animals having the DNA molecules of the invention integrated at a predetermined location in a chromosome by homologous recombination are also encompassed by the invention. Methods to regulate the expression of a tet operator linked gene of interest by administering tetracycline or a tetracycline analogue to an animal of the invention are also disclosed. The regulatory system of the invention allows for conditional inactivation or modulation of expression of a gene of interest in a host cell or animal.
摘要翻译：携带两个转基因的转基因动物，第一编码包含直接或间接在真核细胞中活化的tet阻遏物和多肽的反式激活因子融合蛋白，第二编码包含与可操作地连接至少一个tet操纵子的最小启动子可操作地连接的基因序列。还公开了通过同源重组将编码本发明的反式激活物的多核苷酸序列整合到第二靶DNA分子内的预定位置的分离的DNA分子（例如靶向载体）。通过同源重组将具有整合在染色体中预定位置的本发明的DNA分子的转基因动物也包括在本发明中。还公开了通过向本发明的动物施用四环素或四环素类似物来调节所关注的tet操纵子连接基因的表达的方法。本发明的调节系统允许在宿主细胞或动物中有条件地失活或调控感兴趣的基因的表达。

2. 发明专利

AU684524B2 Tight control of gene expression in eucaryotic cells by tetracycline-responsive promoters 未知
公开(公告)号：AU684524B2
公开(公告)日：1997-12-18
申请号：AU7108194
申请日：1994-06-14
申请人： BASF AG , BUJARD HERMANN , GOSSEN MANFRED
发明人： BUJARD HERMANN , GOSSEN MANFRED , SALFELD JOCHEN G , VOSS JEFFREY W
IPC分类号： A01K67/027 , A61K48/00 , C07K14/00 , C12N5/08 , C12N5/10 , C12N15/00 , C12N15/09 , C12N15/31 , C12N15/62 , C12N15/63 , C12N15/85 , C12R1/91 , C12N15/12 , C12N15/90 , C12N1/19 , C12N1/15
摘要： A method for regulating expression of a tet operator-linked gene in a cell of a subject is disclosed. In one embodiment, the method involves introducing into the cell a nucleic acid molecule encoding a tetracycline-controllable transactivator (tTA), the tTA comprising a Tet repressor operably linked to a polypeptide which directly or indirectly activates transcription in eucaryotic cells; and modulating the concentration of a tetracycline, or analogue thereof, in the subject. Alternatively, in another embodiment, the method involves obtaining the cell from the subject, introducing into the cell a first nucleic acid molecule which operatively links a gene to at least one tet operator sequence, introducing into the cell a second nucleic acid molecule encoding a tTA, to form a modified cell, administering the modified cell to the subject, and modulating the concentration of a tetracycline, or analogue thereof, in the subject. The first and second nucleic acid molecule can be within a single molecule (e.g., in the same vector) or on separate molecules.

3. 发明专利

CA2165162A1 Tight Control of Gene Expression in Eucaryotic Cells by Tetracycline-Responsive Promoters 未知
公开(公告)号：CA2165162A1
公开(公告)日：1994-12-22
申请号：CA2165162
申请日：1994-06-14
申请人： BASF AG , BUJARD HERMANN , GOSSEN MANFRED
发明人： BUJARD HERMANN , GOSSEN MANFRED , SALFELD JOCHEN G , VOSS JEFFREY W
IPC分类号： A01K67/027 , A61K48/00 , C07K14/00 , C12N5/08 , C12N5/10 , C12N15/00 , C12N15/09 , C12N15/31 , C12N15/62 , C12N15/63 , C12N15/85 , C12R1/91
摘要： A method for regulating expression of a tet operator-linked gene in a cell of a subject is disclosed. In one embodiment, the method involves introducing into the cell a nucleic acid molecule encoding a tetracycline-controllable transactivator (tTA), the tTA comprising a Tet repressor operably linked to a polypeptide which directly or indirectly activates transcription in eucaryotic cells; and modulating the concentration of a tetracycline, or analogue thereof, in the subject. Alternatively, in another embodiment, the method involves obtaining the cell from the subject, introducing into the cell a first nucleic acid molecule which operatively links a gene to at least one tet operator sequence, introducing into the cell a second nucleic acid molecule encoding a tTA, to form a modified cell, administering the modified cell to the subject, and modulating the concentration of a tetracycline, or analogue thereof, in the subject. The first and second nucleic acid molecule can be within a single molecule (e.g., in the same vector) or on separate molecules.

4. 发明申请

WO2010034487A3 MEANS FOR INHIBITING THE EXPRESSION OF ORC-1 审中-公开
标题翻译：抑制ORC-1表达的手段
公开(公告)号：WO2010034487A3
公开(公告)日：2010-05-20
申请号：PCT/EP2009006889
申请日：2009-09-23
申请人： SILENCE THERAPEUTICS AG , GOSSEN MANFRED , SANTEL ANSGAR , KAUFMANN JOERG
发明人： GOSSEN MANFRED , SANTEL ANSGAR , KAUFMANN JOERG
IPC分类号： C12N15/113
CPC分类号： C12N15/1135 , C12N15/113 , C12N2310/14
摘要： The present invention is related to a nucleic acid molecule comprising a double-stranded structure, whereby the double-stranded structure comprises a first strand and a second strand, whereby the first strand comprises a first stretch of contiguous nucleotides and said first stretch is at least partially complementary to a target nucleic acid, and whereby the second strand comprises a second stretch of contiguous nucleotides and said second stretch is at least partially complementary to the first stretch, whereby the first stretch comprises a nucleic acid sequence which is at least complementary to a nucleotide core sequence of the nucleic acid sequence according to SEQ. ID.No. 1, whereby the nucleotide core sequence comprises the nucleotide sequence from nucleotide positions 1755 to 1763 of SEQ. ID.No 1; from nucleotide positions 1904 to 1912 of SEQ.ID.No.l; from nucleotide positions 1905 to 1913 of SEQ.ID.No.l; from nucleotide positions 2548 to 2556 of SEQ.ID.No.l whereby the first stretch is additionally at least partially complementary to a region preceding the 5' end of the nucleotide core sequence and/or to a region following the 3' end of the nucleotide core sequence.
摘要翻译：本发明涉及包含双链结构的核酸分子，其中双链结构包含第一链和第二链，其中第一链包含第一段连续核苷酸，并且所述第一段至少为与靶核酸部分互补，并且其中第二链包含第二段连续核苷酸，并且所述第二段与第一段至少部分互补，由此第一段包含至少与第二段互补的核酸序列根据SEQ.ID.NO.1的核酸序列的核苷酸核心序列。证件号码。 1，其中所述核苷酸核心序列包含SEQ.ID.NO.1的核苷酸位置1755至1763的核苷酸序列。 ID.No 1; 从SEQ.ID.No.1的核苷酸位置1904至1912; 从SEQ.ID.No.1的核苷酸位置1905至1913; 从SEQ.ID.No.1的核苷酸位置2548至2556，其中第一段另外至少部分地与核苷酸核心序列的5'末端之前的区域和/或跟随该序列的3'末端之后的区域互补核苷酸核心序列。

5. 发明专利

CA2294598C TRANSCRIPTIONAL ACTIVATORS WITH GRADED TRANSACTIVATION POTENTIAL 未知
公开(公告)号：CA2294598C
公开(公告)日：2008-09-23
申请号：CA2294598
申请日：1998-07-01
申请人： BASF AG , BARON UDO
发明人： BUJARD HERMANN , GOSSEN MANFRED , BARON UDO
IPC分类号： A01K67/027 , C12N15/62 , A61K48/00 , C07K14/035 , C07K14/72 , C07K19/00 , C12N1/15 , C12N1/19 , C12N1/21 , C12N5/10 , C12N15/09 , C12N15/38 , C12N15/63 , C12N15/67 , C12N15/85
摘要： Transcriptional activators which differ in their activation potential by more than 3 orders of magnitude are provided. The transactivators are fusions between a DNA binding protein (e.g., a Tet repressor) and minimal transcriptional activation domains derived from Herpes simplex virus protein 16 (VP16). Substitution mutations at amino acid position 442 within the minimal VP16 domain provide transactivators with differing transactivation ability. Moreover, chimeric activation domains comprising both wild type and mutant minimal VP16 domains provide additional variants with differing transactivation ability. Various aspects of the invention pertain to nucleic acid molecules, vectors, host cells, fusion proteins, transgenic and homologous recombinant organisms and methods of regulating gene transcription.

6. 发明专利

AU755417B2 Transcriptional activators with graded transactivation potential 未知
公开(公告)号：AU755417B2
公开(公告)日：2002-12-12
申请号：AU8182598
申请日：1998-07-01
申请人： BASF AG
发明人： BARON UDO , GOSSEN MANFRED , BUJARD HERMANN
IPC分类号： A01K67/027 , A61K48/00 , C07K14/035 , C07K14/72 , C07K19/00 , C12N1/15 , C12N1/19 , C12N1/21 , C12N5/10 , C12N15/09 , C12N15/63 , C12N15/85 , C12N15/00 , C12N15/38 , C12N15/62 , C12N15/67 , C12Q1/68
摘要： Transcriptional activators which differ in their activation potential by more than 3 orders of magnitude are provided. The transactivators are fusions between a DNA binding protein (e.g., a Tet repressor) and minimal transcriptional activation domains derived from Herpes simplex virus protein 16 (VP16). Substitution mutations at amino acid position 442 within the minimal VP16 domain provide transactivators with differing transactivation ability. Moreover, chimeric activation domains comprising both wild type and mutant minimal VP16 domains provide additional variants with differing transactivation ability. Various aspects of the invention pertain to nucleic acid molecules, vectors, host cells, fusion proteins, transgenic and homologous recombinant organisms and methods of regulating gene transcription.

7. 发明专利

CA2193122C TETRACYCLINE-REGULATED TRANSCRIPTIONAL MODULATORS 未知
公开(公告)号：CA2193122C
公开(公告)日：2005-08-23
申请号：CA2193122
申请日：1995-06-29
申请人： BASF AG , KNOLL AG
发明人： BUJARD HERMANN , GOSSEN MANFRED
IPC分类号： A01K67/027 , A61K48/00 , C07K14/00 , C07K14/035 , C07K14/195 , C07K14/245 , C07K19/00 , C12N1/15 , C12N1/19 , C12N5/10 , C12N15/09 , C12N15/11 , C12N15/12 , C12N15/62 , C12N15/63 , C12N15/67 , C12N15/85 , C12N15/79 , A01H5/00 , A61K31/70 , C12N15/31 , C12N15/38
摘要： Nucleic acid molecules and proteins useful for regulating the expression of genes in eukaryotic cells and organisms are disclosed. Theinvention provides a transcriptional activator fusion protein which binds ro tet operator sequences and stimuiares transcription of a let operator-linked gene in the presence but not the absence, of tetracycline (o r analogue thereof). The invention further provides transcriptional inhibitor fusion proteins which inhibit transcription of a let operaror-(ink ed gene in a regulated manner. In one embodiment, the inhibitor fusion protein hinds to tet operator sequences in the absence, but not the presence, of tetracycline (or analogue). In another embodiment, the inhibitor fusion protein binds to tet operator sequences in the presence, bu t not the absence, of tetracycline (or analogue). The transcriptional activator and inhibitor fusion proteins of the invention can be used in combination to regulate expression of one or multiple tet operator-linked genes. Novel tet operator-containing transcription units whi ch allow for coordinate or independent tetracycline-regulated expression of two or more genes by the transcriptional modulators of the invention are also disclosed. Kits including the components of the regulatory system are also encompassed by the invention.

8. 发明专利

AU3092395A Tetracycline-regulated transcriptional modulators 未知
公开(公告)号：AU3092395A
公开(公告)日：1996-01-25
申请号：AU3092395
申请日：1995-06-29
申请人： BASF AG , KNOLL AG
发明人： BUJARD HERMANN , GOSSEN MANFRED
IPC分类号： A01K67/027 , A61K48/00 , C07K14/00 , C07K14/035 , C07K14/195 , C07K14/245 , C07K19/00 , C12N1/15 , C12N1/19 , C12N5/10 , C12N15/09 , C12N15/11 , C12N15/12 , C12N15/62 , C12N15/63 , C12N15/67 , C12N15/85 , C12N15/00
摘要： Nucleic acid molecules and proteins useful for regulating the expression of genes in eukaryotic cells and organisms are disclosed. The invention provides a transcriptional activator fusion protein which binds to tet operator sequences and stimulates transcription of a tet operator-linked gene in the presence, but not the absence, of tetracycline (or analogue thereof). The invention further provides transcriptional inhibitor fusion proteins which inhibit transcription of a tet operator-linked gene in a regulated manner. In one embodiment, the inhibitor fusion protein binds to tet operator sequences in the absence, but not the presence, of tetracycline (or analogue). In another embodiment, the inhibitor fusion protein binds to tet operator sequences in the presence, but not the absence, of tetracycline (or analogue). The transcriptional activator and inhibitor fusion proteins of the invention can be used in combination to regulate expression of one or multiple tet operator-linked genes. Novel tet operator-containing transcription units which allow for coordinate or independent tetracycline-regulated expression of two or more genes by the transcriptional modulators of the invention are also disclosed. Kits including the components of the regulatory system are also encompassed by the invention.

9. 发明专利

CA2193122A1 TETRACYCLINE-REGULATED TRANSCRIPTIONAL MODULATORS 未知
公开(公告)号：CA2193122A1
公开(公告)日：1996-01-18
申请号：CA2193122
申请日：1995-06-29
申请人： BASF AG , KNOLL AG
发明人： BUJARD HERMANN , GOSSEN MANFRED
IPC分类号： A01K67/027 , A61K48/00 , C07K14/00 , C07K14/035 , C07K14/195 , C07K14/245 , C07K19/00 , C12N1/15 , C12N1/19 , C12N5/10 , C12N15/09 , C12N15/11 , C12N15/12 , C12N15/62 , C12N15/63 , C12N15/67 , C12N15/85 , C12N15/79 , A01H5/00 , A61K31/70 , C12N15/31 , C12N15/38
摘要： Nucleic acid molecules and proteins useful for regulating the expression of genes in eukaryotic cells and organisms are disclosed. Theinvention provides a transcriptional activator fusion protein which binds to tet operator sequences and stimulates transcription of a tet operator-linked gene in the presence, but not the absence, of tetracycline (or analogue thereof). The invention further provides transcriptional inhibitor fusion proteins which inhibit transcription of a tet operator-linked gene in a regulated manner. In one embodiment, the inhibitor fusion protein binds to tet operator sequences in the absence, but not the presence, of tetracycline (or analogue). In another embodiment, the inhibitor fusion protein binds to tet operator sequences in the presence, but not the absence, of tetracycline (or analogue). The transcriptional activator and inhibitor fusion proteins of the invention can be used in combination to regulate expression of one or multiple tet operator-linked genes. Novel tet operatorcontaining transcription units which allow for coordinate or independent tetracycline-regulated expression of two or more genes by the transcriptional modulators of the invention are also disclosed. Kits including the components of the regulatory system are also encompassed by the invention.

10. 发明专利

AU8182598A Transcriptional activators with graded transactivation potential 未知
公开(公告)号：AU8182598A
公开(公告)日：1999-01-25
申请号：AU8182598
申请日：1998-07-01
申请人： BASF AG , BARON UDO
发明人： BARON UDO , GOSSEN MANFRED , BUJARD HERMANN
IPC分类号： A01K67/027 , A61K48/00 , C07K14/035 , C07K14/72 , C07K19/00 , C12N1/15 , C12N1/19 , C12N1/21 , C12N5/10 , C12N15/09 , C12N15/63 , C12N15/85 , C12N15/00 , C12N15/38 , C12N15/62 , C12N15/67 , C12Q1/68
摘要： Transcriptional activators which differ in their activation potential by more than 3 orders of magnitude are provided. The transactivators are fusions between a DNA binding protein (e.g., a Tet repressor) and minimal transcriptional activation domains derived from Herpes simplex virus protein 16 (VP16). Substitution mutations at amino acid position 442 within the minimal VP16 domain provide transactivators with differing transactivation ability. Moreover, chimeric activation domains comprising both wild type and mutant minimal VP16 domains provide additional variants with differing transactivation ability. Various aspects of the invention pertain to nucleic acid molecules, vectors, host cells, fusion proteins, transgenic and homologous recombinant organisms and methods of regulating gene transcription.

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