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    Use of trans-activation and CIS-activation to modulate the persistence of expression of a transgene
    12.
    发明申请
    Use of trans-activation and CIS-activation to modulate the persistence of expression of a transgene 失效

    公开(公告)号：US20020031823A1

    公开(公告)日：2002-03-14

    申请号：US09873486

    申请日：2001-06-04

    Applicant: GenVec, Inc.

    Inventor： Douglas E. Brough ,  Imre Kovesdi

    IPC: A61K048/00 ,  C12N015/86

    CPC classification number: C12N15/86 ,  C07K14/005 ,  C12N15/63 ,  C12N2710/10322 ,  C12N2710/10345 ,  C12N2710/16622 ,  C12N2830/60 ,  C12N2840/60

    Abstract: Provided are methods of modulating the persistence of the expression in a cell of a transgene, such as a transgene in a non-Herpes vector or in at least E4null adenoviral vector, and related systems. One method comprises contacting the cell with a non-Herpes vector comprising and expressing a gene encoding HSV ICP0, whereupon expression of HSV ICP0 the persistence of expression of the transgene is modulated. Further provided is a system for modulating the persistence of expression of a transgene, which system comprises a non-Herpes vector comprising (i) a gene encoding HSV ICP0 and (ii) a transgene, wherein the HSV ICP0 modulates the persistence of expression of the transgene and either the non-Herpes vector comprises the transgene or the system further comprises a vector, in which case the vector comprises the transgene. Another method comprises contacting the cell with an at least E4null adenoviral vector comprising (i) a transgene and (ii) a gene encoding a trans-acting factor, wherein the trans-acting factor modulates the persistence of expression of the transgene and the gene encoding the trans-acting factor is not from the E4 region of an adenovirus. Yet another method comprises contacting a cell simultaneously or sequentially with (i) an at least E4null adenoviral vector comprising a transgene and (ii) a viral vector comprising a gene encoding a trans-acting factor, which is not from the E4 region of an adenovirus and which modulates the persistence of expression of the transgene. Also provided is a system for modulating the persistence of expression of a transgene in an at least E4null adenoviral vector, which system comprises (i) an at least E4null adenoviral vector comprising a transgene and (ii) a gene encoding a trans-acting factor, wherein the gene encoding the trans-acting factor is not from the E4 region of an adenovirus, the trans-acting factor modulates the persistence of expression of the transgene, and either the at least E4null adenoviral vector comprises the gene encoding the trans-acting factor or the system comprises a viral vector, in which case the viral vector comprises the gene encoding the trans-acting factor.

    Materials and methods for treating disorders of the ear
    13.
    发明申请
    Materials and methods for treating disorders of the ear 审中-公开
    用于治疗耳朵疾病的材料和方法

    公开(公告)号：US20040166091A1

    公开(公告)日：2004-08-26

    申请号：US10373249

    申请日：2003-02-24

    Applicant: GenVec, Inc.

    Inventor： Douglas E. Brough

    IPC: A61K048/00 ,  C12N015/861

    CPC classification number: A61K38/17 ,  A61K38/00 ,  A61K48/005 ,  A61P27/00 ,  C07K14/4702 ,  C12N7/00 ,  C12N15/86 ,  C12N2501/60 ,  C12N2710/10343

    Abstract: The invention is directed to a method of changing the sensory perception of an animal. The method comprises administering an expression vector comprising a nucleic acid sequence encoding an atonal-associated factor, which is expressed to produce the atonal-associated factor resulting in generation of hair cells that allow perception of stimuli in the inner ear. Also provided is a method of generating a hair cell in differentiated sensory epithelia in vivo. The method comprises contacting differentiated sensory epithelial cells with an adenoviral vector (a) deficient in one or more replication-essential gene functions of the E1 region and E4 region, (b) comprising a spacer in the E4 region, and (c) comprising a nucleic acid sequence encoding an atonal-associated factor. The nucleic acid sequence is expressed to produce the atonal-associated factor such that a hair cell is generated. An adenoviral vector encoding an atonal-associated factor also is provided.

    Abstract translation: 本发明涉及一种改变动物的感觉知觉的方法。 所述方法包括施用包含编码无关联因子的核酸序列的表达载体，所述核酸序列被表达以产生导致产生能够感知内耳中的刺激的毛细胞的无关性因子。 还提供了一种在体内在分化感觉上皮细胞中产生毛细胞的方法。 该方法包括使分化的感觉上皮细胞与E1区和E4区的一个或多个复制必需基因功能缺陷的腺病毒载体（a）接触，（b）在E4区中包含间隔基，和（c）包含 编码无关联因子的核酸序列。 表达核酸序列以产生无创因子，从而产生毛细胞。 还提供了编码无关联因子的腺病毒载体。

    Replication deficient adenoviral TNF vector
    14.
    发明申请
    Replication deficient adenoviral TNF vector 审中-公开

    公开(公告)号：US20030175245A1

    公开(公告)日：2003-09-18

    申请号：US10424638

    申请日：2003-04-25

    Applicant: GenVec, Inc.

    Inventor： Douglas E. Brough ,  C. Richter King ,  Imre Kovesdi ,  Jasper J. Schaible

    IPC: A61K048/00 ,  C12N007/00 ,  C12N015/861

    CPC classification number: C12N15/86 ,  A61K38/191 ,  A61K48/00 ,  C12N2710/10343 ,  C12N2810/40

    Abstract: An adenoviral vector comprising (a) an adenoviral genome deficient in the E4 region of the adenoviral genome, (b) a nucleic acid sequence coding for TNF, and (c) a radiation inducible promoter operably linked to the nucleic acid sequence coding for TNF. This invention also provides an adenoviral vector comprising (a) an adenoviral genome deficient in the E4 region of the adenoviral genome, (b) a nucleic acid sequence coding for TNF, and (c) a spacer element of at least 15 base pairs in the E4 region of the adenoviral genome. A method of producing an adenoviral vector and a method of treating a tumor or cancer in a host comprising administering an anti-cancer or anti-tumor effective amount of the adenoviral vector of the present invention also is provided.

    Method and composition for targeting an adenoviral vector
    15.
    发明申请
    Method and composition for targeting an adenoviral vector 审中-公开
    用于靶向腺病毒载体的方法和组合物

    公开(公告)号：US20030099619A1

    公开(公告)日：2003-05-29

    申请号：US10304160

    申请日：2002-11-25

    Applicant: GenVec, Inc.

    Inventor： Thomas J. Wickham ,  Imre Kovesdi ,  Petrus W. Roelvink ,  David Einfeld ,  Douglas E. Brough ,  Alena Lizonova

    IPC: A61K048/00 ,  C12Q001/70 ,  C12N015/861 ,  C07K014/705 ,  C07K014/075

    CPC classification number: C12N15/86 ,  A61K48/00 ,  C12N2710/10343 ,  C12N2710/10345 ,  C12N2810/40 ,  C12N2810/405 ,  C12N2810/60 ,  C12N2810/80 ,  C12N2830/008

    Abstract: The invention provides adenoviral coat proteins comprising various non-native ligands. Further, the present invention provides an adenoviral vector that elicits less reticulo-endothelial system (RES) clearance in a host animal than a corresponding wild-type adenovirus. Also provided by the invention is a system comprising a cell having a non-native cell-surface receptor and a virus having a non-native ligand, wherein the non-native ligand of the virus binds the non-native cell-surface receptor of the cell. Using this system, a virus can be propagated. Further provided by the invention is a method of controlled gene expression utilizing selectively replication competence, a method of assaying for gene function, a method of isolating a nucleic acid, and a method of identifying functionally related coding sequences. Additionally, the invention provides a cell-surface receptor, which facilitates internalization.

    Abstract translation: 本发明提供了包含各种非天然配体的腺病毒外壳蛋白。 此外，本发明提供了一种腺病毒载体，其在宿主动物中比相应的野生型腺病毒引起较少的网状内皮系统（RES）清除。 本发明还提供了一种包含具有非天然细胞表面受体的细胞和具有非天然配体的病毒的系统的系统，其中所述病毒的非天然配体结合所述非天然细胞表面受体的非天然细胞表面受体 细胞。 使用该系统可以传播病毒。 本发明进一步提供了利用选择性复制能力的受控基因表达的方法，基因功能测定方法，分离核酸的方法和识别功能相关编码序列的方法。 另外，本发明提供了促进内化的细胞表面受体。

    Adenovector complementing cells
    16.
    发明申请
    Adenovector complementing cells 有权
    Adenovector补体细胞

    公开(公告)号：US20030054553A1

    公开(公告)日：2003-03-20

    申请号：US09910828

    申请日：2001-07-23

    Applicant: GenVec, Inc.

    Inventor： Douglas E. Brough ,  Jason G.D. Gall ,  Imre Kovesdi

    IPC: C12N015/861 ,  C12N007/00 ,  C12N005/08

    CPC classification number: C12N15/86 ,  C12N7/00 ,  C12N2710/10343 ,  C12N2710/10352

    Abstract: The invention provides cells, particularly NCI-H460 cells and Calu-1 cells, for the propagation of replication-deficient adenoviral vectors. The cells are lung carcinomas with either a wild-type p53 gene or a heterozygous K-ras mutation. The cells comprise at least one adenoviral nucleic acid sequence, which upon expression produces a gene product that complements for at least one essential gene function of one or more regions of an adenoviral genome so as to propagate a replication-deficient adenoviral vector comprising an adenoviral genome deficient in the at least one essential gene function of the one or more regions when present in the cell.

    Abstract translation: 本发明提供用于增殖复制缺陷型腺病毒载体的细胞，特别是NCI-H460细胞和Calu-1细胞。 细胞是具有野生型p53基因或杂合K-ras突变的肺癌。 细胞包含至少一种腺病毒核酸序列，其在表达时产生补充腺病毒基因组的一个或多个区域的至少一个必需基因功能的基因产物，以便繁殖包含腺病毒基因组的复制缺陷型腺病毒载体 当存在于细胞中时，一个或多个区域的至少一个必需基因功能缺陷。

    Methods of preparing and using a viral vector library
    19.
    发明申请
    Methods of preparing and using a viral vector library 有权
    制备和使用病毒载体文库的方法

    公开(公告)号：US20010026794A1

    公开(公告)日：2001-10-04

    申请号：US09780526

    申请日：2001-02-09

    Applicant: GenVec, Inc.

    Inventor： Imre Kovesdi ,  Duncan L. McVey ,  Thomas J. Wickham ,  Joseph T. Bruder ,  Douglas E. Brough

    IPC: A61K048/00 ,  C12Q001/70 ,  C12N007/01

    CPC classification number: C12N15/1093 ,  A61K48/00 ,  C12N15/86 ,  C12N2710/10343 ,  C12N2710/10345 ,  C12N2810/40

    Abstract: The present invention provides a library of viral vectors, wherein each member comprises a first heterologous DNA encoding a first gene product and a second heterologous DNA encoding a second gene product. The first heterologous DNA is common to each member of the library, while the second heterologous DNA varies between members of the library. The present invention additionally provides a method of constructing a library of viral vectors. The method comprises carrying out homologous recombination between a first DNA molecule and a second DNA molecule to form a pool of intermediate viral vector genomes. One or more linear third DNA molecules are ligated into the pool of intermediate viral genomes to produce a library of viral vector genomes. Alternatively, homologous recombination between linear DNA molecules and recipient DNA molecules produces a library of viral vector genomes. The library of viral vector genomes is converted into a library of viral vectors.

    Abstract translation: 本发明提供病毒载体文库，其中每个成员包含编码第一基因产物的第一异源DNA和编码第二基因产物的第二异源DNA。 第一个异源DNA对于文库的每个成员是共同的，而第二异源DNA在文库的成员之间是不同的。 本发明另外提供构建病毒载体文库的方法。 该方法包括在第一DNA分子和第二DNA分子之间进行同源重组以形成中间病毒载体基因组池。 将一个或多个线性第三DNA分子连接到中间病毒基因组池中以产生病毒载体基因组文库。 或者，线性DNA分子和受体DNA分子之间的同源重组产生病毒载体基因组文库。 将病毒载体基因组文库转化为病毒载体文库。

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