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    Method of using adenoviral vectors with increased persistence in vivo
    1.
    发明申请
    Method of using adenoviral vectors with increased persistence in vivo 审中-公开
    使用体内持续性增加的腺病毒载体的方法

    公开(公告)号：US20040167088A1

    公开(公告)日：2004-08-26

    申请号：US10374271

    申请日：2003-02-25

    Applicant: GenVec, Inc.

    Inventor： Thomas J. Wickham ,  Masaki Akiyama

    IPC: A61K048/00 ,  C12N015/861

    CPC classification number: C12N15/86 ,  A61K48/00 ,  C12N2710/10322 ,  C12N2710/10343 ,  C12N2710/10345 ,  C12N2810/405 ,  C12N2810/50

    Abstract: The invention provides a method of expressing an exogenous nucleic acid in a mammal. The method comprises slowly releasing into the bloodstream a dose of replication-deficient or conditionally-replicating adenoviral vector having reduced ability to transduce mesothelial cells and hepatocytes. The normalized average bloodstream concentration of the adenovirus over 24 hours post-administration is at least about 1%. Alternatively, the normalized average bloodstream concentration over 24 hours post-administration is at least about 5-fold greater than the normalized average bloodstream concentration for an equivalent dose of a wild-type adenoviral vector. A method of destroying tumor cells in a mammal also is provided.

    Abstract translation: 本发明提供了在哺乳动物中表达外源核酸的方法。 该方法包括缓慢释放一定剂量的复制缺陷型或条件复制型腺病毒载体，其具有降低转导间皮细胞和肝细胞的能力。 给药后24小时内腺病毒的归一化平均血流浓度为至少约1％。 或者，给药后24小时内的标准化平均血流浓度比相当剂量的野生型腺病毒载体的归一化平均血流浓度高至少约5倍。 还提供了一种破坏哺乳动物肿瘤细胞的方法。

    Method and composition for targeting an adenoviral vector
    3.
    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。

    Targeting adenovirus with use of constrained peptide motifs
    5.
    发明申请
    Targeting adenovirus with use of constrained peptide motifs 有权
    使用受限肽基序靶向腺病毒

    公开(公告)号：US20020151027A1

    公开(公告)日：2002-10-17

    申请号：US09969192

    申请日：2001-10-01

    Applicant: GenVec, Inc.

    Inventor： Thomas J. Wickham ,  Petrus W. Roelvink ,  Imre Kovesdi

    IPC: C12N015/861 ,  C12N009/50 ,  C12N007/01

    CPC classification number: C12N7/00 ,  A61K38/00 ,  A61K48/00 ,  C07K14/005 ,  C07K2319/00 ,  C12N15/86 ,  C12N2710/10322 ,  C12N2710/10343 ,  C12N2710/10345 ,  C12N2810/40 ,  C12N2810/405 ,  C12N2810/60

    Abstract: The present invention provides a chimeric adenovirus fiber protein, which differs from the wild-type coat protein by the introduction of a nonnative amino acid sequence in a conformationally-restrained manner. Such a chimeric adenovirus fiber protein according to the invention is able to direct entry into cells of a vector comprising the chimeric fiber protein that is more efficient than entry into cells of a vector that is identical except for comprising a wild-type adenovirus fiber protein rather than the chimeric adenovirus fiber protein. The nonnative amino acid sequences encodes a peptide motif that comprises an epitope for an antibody, or a ligand for a cell surface receptor, that can be employed in cell targeting. The present invention also pertains to vectors comprising such a chimeric adenovirus fiber protein, and to methods of using such vectors.

    Abstract translation: 本发明提供了一种嵌合腺病毒纤维蛋白，其通过以构象约束的方式引入非氨基酸序列而与野生型外壳蛋白不同。 根据本发明的这种嵌合腺病毒纤维蛋白能够直接进入包含嵌合纤维蛋白质的载体的细胞，该载体比除了包含野生型腺病毒纤维蛋白的载体的细胞进入更有效，而不是包含野生型腺病毒纤维蛋白 比嵌合腺病毒纤维蛋白。 非氨基酸序列编码包含可用于细胞靶向的抗体表位或细胞表面受体配体的肽基序。 本发明还涉及包含这种嵌合腺病毒纤维蛋白的载体，以及使用这些载体的方法。

    Methods of preparing and using a viral vector library
    6.
    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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