Thymidine Kinase Mutants and Fusion Proteins Having Thymidine Kinase and Guanylate Kinase Activities

    公开(公告)号:US20130011903A1

    公开(公告)日:2013-01-10

    申请号:US13538503

    申请日:2012-06-29

    申请人: Margaret E. Black

    发明人: Margaret E. Black

    IPC分类号: C12N9/96

    摘要: The present invention provides isolated nucleic acid molecules encoding a Herpesviridae thymidine kinase enzyme comprising one or more mutations, at least one of the mutations encoding an amino acid substitution located toward the N-terminus from a DRH nucleoside binding site which increases a biological activity of the thymidine kinase, as compared to unmutated thymidine kinase. Such mutations include amino acid substitutions within a Q substrate binding domain which increases a biological activity of the thymidine kinase, as compared to unmutated thymidine kinase. Within a further aspect, fusion proteins are provided which have both guanylate kinase and thymidine kinase biological properties. Also provided are vectors suitable for expressing such DNA molecules, as well as methods for utilizing such vectors.

    Transgenic mice generated by transposition and uses thereof
    3.
    发明授权
    Transgenic mice generated by transposition and uses thereof 失效
    通过转座产生的转基因小鼠及其用途

    公开(公告)号:US07709696B2

    公开(公告)日:2010-05-04

    申请号:US10887636

    申请日:2004-07-09

    IPC分类号: C12N15/00 A01K67/027

    摘要: A method of inducing transposition in a transgenic embryo, sperm and egg is described, comprising the steps of (a) generating a first adult transgenic organism comprising within its genome one or more copies of a transposon; (b) generating a second adult transgenic organism comprising within its genome one or more copies of a gene encoding a transposase cognate for the transposon and/or a sequence capable of regulating expression of the gene encoding the transposase; (c) crossing the first adult transgenic organism with the second transgenic adult organism to provide a progeny which comprises, in the genome of one or more of its cells, both (i) one or more copies of the transposon and (ii) a gene encoding a transposase cognate for the transposon, wherein the gene encoding the transposase is under the control of one or more inducible regulatory sequences which permit expression of the transposase, and (d) expressing the gene encoding the transposase in the embryo, sperm or egg to cause mobilization of the transposon within a portion of the tissues or cells of the progeny. Using the method, mobilization of a transposon can advantageously be induced at predetermined stages of development of an embryo, sperm or egg and the mutated gene of a single cell may be replicated in subsequent cell divisions, resulting in groups of cells which are essentially homogenous for the transposed gene.

    摘要翻译: 描述了在转基因胚胎,精子和卵中诱导转座的方法,其包括以下步骤:(a)产生第一成体转基因生物体,其在其基因组中包含转座子的一个或多个拷贝; (b)产生第二成体转基因生物体,其在其基因组中包含编码与转座子相关的转座酶的基因的一个或多个拷贝和/或能够调节编码转座酶基因表达的序列; (c)将第一成体转基因生物与第二转基因成体生物体交叉以提供后代,其在一个或多个细胞的基因组中包含(i)转座子的一个或多个拷贝和(ii)基因 编码转座子的转座酶,其中编码转座酶的基因处于允许转座酶表达的一种或多种可诱导调节序列的控制下,和(d)在胚胎,精子或卵中表达编码转座酶的基因, 导致转座子在子代的组织或细胞的一部分内的动员。 使用该方法,可以有利地在胚胎,精子或卵的发育的预定阶段诱导转座子的动员,并且可以在随后的细胞分裂中复制单细胞的突变基因,导致基本上均匀的细胞群 转座基因。

    TARGETING OF HERPES SIMPLEX VIRUS TO SPECIFIC RECEPTORS
    5.
    发明申请
    TARGETING OF HERPES SIMPLEX VIRUS TO SPECIFIC RECEPTORS 有权
    将特定病毒的简单病毒定向到特定受体

    公开(公告)号:US20090136452A1

    公开(公告)日:2009-05-28

    申请号:US12065455

    申请日:2006-08-30

    摘要: The invention relates to engineered Herpes simplex virus (HSV) particles that are targeted to one or more specific binding pair members, such as receptors. Also, recombinant vectors for producing such HSV particles are provided. By reducing the affinity of HSV for its natural receptor(s) and increasing the affinity for a selected receptor, the HSV particles of the invention are useful for targeting cells that express the selected receptor, which itself may be a product of genetic engineering. The ability to selectively target cells render the HSV particles. particularly useful in selectively diagnosing, treating, and imaging cells bearing the selected binding pair member, such as a receptor. The invention also provides for polynucleotide-based therapy to cells bearing the selected binding pair member such as a receptor.

    摘要翻译: 本发明涉及靶向一种或多种特异性结合对成员(例如受体)的工程化单纯疱疹病毒(HSV)颗粒。 此外,提供了用于生产这种HSV颗粒的重组载体。 通过降低HSV对其天然受体的亲合力并增加对所选受体的亲和力,本发明的HSV颗粒可用于靶向表达所选受体的细胞,其本身可能是遗传工程的产物。 选择性靶向细胞的能力使HSV颗粒。 特别可用于选择性地诊断,治疗和成像携带所选择的结合对成员例如受体的细胞。 本发明还提供了携带选定结合对成员例如受体的细胞的基于多核苷酸的治疗。

    Compositions and Methods for Treating Neurological Diseases
    8.
    发明申请
    Compositions and Methods for Treating Neurological Diseases 审中-公开
    治疗神经疾病的组合物和方法

    公开(公告)号:US20070264280A1

    公开(公告)日:2007-11-15

    申请号:US10578561

    申请日:2004-11-08

    摘要: The invention includes therapeutic compositions and methods useful in the treatment of neurodegenerative diseases, such as those characterized by accumulation of extracellular plaques. Such neurodegenerative diseases include Alzheimer's disease. The compositions of the invention include HSVAβ/TtxFC, which can be used to deliver effective therapeutic benefits to a patient without inducing inflammation.

    摘要翻译: 本发明包括可用于治疗神经变性疾病的治疗组合物和方法,例如以细胞外斑块积聚为特征的那些。 这样的神经变性疾病包括阿尔茨海默氏病。 本发明的组合物包括HSVAbeta / TtxFC,其可用于在不诱发炎症的情况下向患者递送有效的治疗益处。

    Methods and compositions for evaluating cell function in sensory neurons
    9.
    发明申请
    Methods and compositions for evaluating cell function in sensory neurons 审中-公开
    用于评估感觉神经元细胞功能的方法和组合物

    公开(公告)号:US20060211021A1

    公开(公告)日:2006-09-21

    申请号:US11361101

    申请日:2006-02-24

    IPC分类号: C12Q1/68 C12N5/08 C12N15/87

    摘要: Methods and compositions are provided for determining whether target, e.g., an endogenous or novel (non-endogenous), nucleic acid sequence of a neuronal cell is involved in sensory function. In practicing the subject methods, a neuronal cell selective vector including a modulating domain for a neuronal cell nucleic acid sequence, optionally having a domain encoding a directly detectable product, is administered to an animal. Sensory function in harvested neuronal cells is then evaluated to determine whether the target nucleic acid sequence is involved in sensory function. Also provided are compositions, kits, and systems for practicing the subject methods.

    摘要翻译: 提供方法和组合物用于确定神经元细胞的靶,例如内源或新颖(非内源)核酸序列是否参与感觉功能。 在实施本发明方法中,向动物施用包含神经元细胞核酸序列的调节结构域(任选地具有编码直接可检测产物的结构域)的神经元细胞选择性载体。 然后评估收获的神经元细胞中的感觉功能,以确定靶核酸序列是否涉及感觉功能。 还提供了用于实践本发明方法的组合物,试剂盒和系统。