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    PHARMACOLOGICALLY INDUCED TRANSGENE ABLATION SYSTEM
    31.
    发明申请
    PHARMACOLOGICALLY INDUCED TRANSGENE ABLATION SYSTEM 审中-公开
    药理学诱导转基因系统

    公开(公告)号：US20130023033A1

    公开(公告)日：2013-01-24

    申请号：US13638015

    申请日：2011-03-28

    申请人： James M. Wilson ,  Shu-Jen Chen ,  Anna P. Tretiakova

    发明人： James M. Wilson ,  Shu-Jen Chen ,  Anna P. Tretiakova

    IPC分类号： C12N7/01 ,  C12N5/10 ,  C12N1/21 ,  C12N15/63

    CPC分类号： C12N15/86 ,  A61K48/0066 ,  C07K2319/715 ,  C07K2319/80 ,  C12N9/22 ,  C12N2750/14143 ,  C12N2800/30 ,  C12N2800/80 ,  C12N2830/002 ,  C12N2830/003 ,  C12N2830/005 ,  C12N2830/006 ,  C12N2830/20 ,  C12N2840/203

    摘要： The present invention relates to gene therapy systems designed for the delivery of a therapeutic product to a subject using replication-defective virus composition(s) engineered with a built-in safety mechanism for ablating the therapeutic gene product, either permanently or temporarily, in response to a pharmacological agent—preferably an oral formulation, e.g., a pill. The invention is based, in part, on the applicants' development of an integrated approach, referred to herein as “PITA” (Pharmacologically Induced Transgene Ablation), for ablating a transgene or negatively regulating transgene expression. In this approach, replication-deficient viruses are used to deliver a transgene encoding a therapeutic product (an RNA or a protein) so that it is expressed in the subject, but can be reversibly or irreversibly turned off by administering the pharmacological agent; e.g., by administration of a small molecule that induces expression of an ablator specific for the transgene or its RNA transcript.

    摘要翻译： 本发明涉及基因治疗系统，其被设计用于使用使用内置安全机制工程改造的复制缺陷病毒组合物将治疗产品递送给受试者，所述安全机制永久地或临时地用于消融治疗性基因产物 药物剂 - 优选口服制剂，例如丸剂。 本发明部分地基于申请人开发综合方法，本文称为PITA（药理学诱导的转基因消融），用于消融转基因或负调节转基因表达。 在这种方法中，使用复制缺陷病毒递送编码治疗产物（RNA或蛋白质）的转基因，使其在受试者中表达，但是可以通过施用药理学试剂来逆转或不可逆地关闭; 例如通过施用诱导特异于转基因或其RNA转录物的消融体表达的小分子。

    ADENO-ASSOCIATED VIRUS (AAV) SEQUENCES AND ISOLATING NOVEL SEQUENCES IDENTIFIED THEREBY
    34.
    发明申请
    ADENO-ASSOCIATED VIRUS (AAV) SEQUENCES AND ISOLATING NOVEL SEQUENCES IDENTIFIED THEREBY 有权
    ADENO相关病毒（AAV）序列和分离的序列识别

    公开(公告)号：US20110151434A1

    公开(公告)日：2011-06-23

    申请号：US12962793

    申请日：2010-12-08

    申请人： GUANGPING GAO ,  James M. Wilson ,  Mauricio R. Alvira

    发明人： GUANGPING GAO ,  James M. Wilson ,  Mauricio R. Alvira

    IPC分类号： C12Q1/70 ,  C12Q1/68 ,  C12N15/63

    CPC分类号： C12N15/86 ,  A61K38/177 ,  A61K38/4846 ,  A61K48/00 ,  C07K14/005 ,  C12N7/00 ,  C12N2750/14121 ,  C12N2750/14122 ,  C12N2750/14143 ,  C12N2750/14151 ,  C12N2750/14152 ,  C12N2750/14162 ,  C12N2750/14171 ,  C12N2830/008 ,  C12N2830/48 ,  C12N2830/85 ,  C12N2830/90 ,  C12Q1/701 ,  C12Q2600/158 ,  C12Y304/21022

    摘要： A method for detecting and isolating AAV sequences in a sample of DNA obtained from tissue or cells is provided, which sample contains DNA and proviral AAV. The method involves subjecting the sample containing DNA to amplification via polymerase chain reaction (PCR) using a first set of primers which specifically amplify a first AAV region. The first AAV region is characterized by having at least 250 nucleotides of AAV capsid nucleic acid sequence, a variable sequence flanked by a sequence of at least 18 nucleotides at the 5′ end of the first AAV region and a sequence of at least 18 nucleotides at the 3′ end of the first AAV region. Each of the 5′ and 3′ at least 18 nucleotides is the same over at least 9 consecutive nucleotides relative to corresponding sequences in an alignment of at least two AAV serotypes. Each of the sets of primers consist of a 5′ primer and a 3′ primer. The method is further useful for identifying AAV sequences in the sample by the presence of amplified proviral AAV sequences.

    摘要翻译： 提供了从组织或细胞获得的DNA样品中检测和分离AAV序列的方法，该样品含有DNA和前病毒AAV。 该方法包括使用特异性扩增第一AAV区域的第一组引物通过聚合酶链反应（PCR）使含有DNA的样品进行扩增。 第一个AAV区的特征在于具有AAV衣壳核酸序列的至少250个核苷酸，在第一AAV区的5'末端侧接至少18个核苷酸的序列的可变序列和至少18个核苷酸的序列 第一个AAV区域的3'端。 相对于至少两种AAV血清型的比对中的相应序列，5'和3'至少18个核苷酸中的每一个在至少9个连续核苷酸上相同。 每组引物由5'引物和3'引物组成。 该方法进一步用于通过扩增的前病毒AAV序列的存在来鉴定样品中的AAV序列。

    Method of testing connectivity using dual operational mode CML latch
    36.
    发明授权
    Method of testing connectivity using dual operational mode CML latch 失效
    使用双操作模式CML锁定测试连接的方法

    公开(公告)号：US07560966B2

    公开(公告)日：2009-07-14

    申请号：US12002878

    申请日：2007-12-19

    申请人： Joseph O. Marsh ,  Joseph Natonio ,  James M. Wilson

    发明人： Joseph O. Marsh ,  Joseph Natonio ,  James M. Wilson

    IPC分类号： H03K3/289

    CPC分类号： H03K3/356043

    摘要： A method of testing connectivity through a plurality of dual purpose current mode logic (“CML”) latch circuits connected in a series is provided. Each of the CML latch circuits are operable to latch at least one output signal at a timing in accordance with at least one clock signal and having a mode control device for operating the CML latch circuit as a buffer amplifier when the at least one clock signal is inactive. The method comprises the steps of activating the mode control devices of each of the CML latches to operate each of the CML latches as a buffer; inputting a first signal to a first CML latch of the series; latching an output signal of a second CML latch of the series, the second CML latch being connected at a point in the series downstream from the first CML latch; and determining whether the output signal changes in accordance with a change in the first signal.

    摘要翻译： 提供了通过串联连接的多个双用途电流模式逻辑（“CML”）锁存电路来测试连接性的方法。 每个CML锁存电路可操作以根据至少一个时钟信号在定时锁存至少一个输出信号，并具有一个模式控制装置，用于当至少一个时钟信号为 不活动 该方法包括以下步骤：激活每个CML锁存器的模式控制装置，以操作每个CML锁存器作为缓冲器; 向所述系列的第一CML锁存器输入第一信号; 锁存串联的第二CML锁存器的输出信号，第二CML锁存器在第一CML锁存器下游的串联点连接; 以及确定所述输出信号是否根据所述第一信号的改变而改变。

    Methods of generating chimeric adenoviruses and uses for such chimeric adenoviruses
    37.
    发明授权
    Methods of generating chimeric adenoviruses and uses for such chimeric adenoviruses 有权
    产生嵌合腺病毒的方法和用于这种嵌合腺病毒的方法

    公开(公告)号：US07491508B2

    公开(公告)日：2009-02-17

    申请号：US10561201

    申请日：2004-06-15

    申请人： Soumitra Roy ,  James M. Wilson

    发明人： Soumitra Roy ,  James M. Wilson

    IPC分类号： C12N15/63 ,  C12N15/64 ,  C12N15/861 ,  C12N5/10 ,  A61K48/00 ,  C12P21/00 ,  C07H21/04 ,  C12Q1/68 ,  C12Q1/70

    CPC分类号： C07K14/005 ,  A61K39/00 ,  A61K39/12 ,  A61K48/00 ,  A61K2039/5256 ,  C12N15/86 ,  C12N2710/10322 ,  C12N2710/10343 ,  C12N2710/10344 ,  C12N2710/10351 ,  C12N2760/14134 ,  C12N2810/6018

    摘要： A method for providing an adenovirus from a serotype which does not grow efficiently in a desired cell line with the ability to grow in that cell line is described. The method involves replacing the left and right termini of the adenovirus with the corresponding termini from an adenovirus which grow efficiently in the desired cell line. At a minimum, the left terminus spans the (5′) inverted terminal repeat, the left terminus spans the E4 region and the (3′) inverted terminal repeat. The resulting chimeric adenovirus contains the internal regions spanning the genes encoding the penton, hexon and fiber from the serotype which does not grow efficiently in the desired cell. Also provided are vectors constructed from novel simian adenovirus sequences and proteins, host cells containing same, and uses thereof.

    摘要翻译： 描述了从在该细胞系中具有生长能力的所需细胞系中不能有效生长的血清型提供腺病毒的方法。 该方法包括用在期望的细胞系中有效生长的腺病毒的相应末端替换腺病毒的左侧和右侧末端。 至少，左终点跨越（5'）反向末端重复，左终点跨越E4区域，（3'）反向末端重复。 所得到的嵌合腺病毒包含跨越编码来自血清型的五邻体，六邻体和纤维的基因的内部区域，其不能在期望的细胞中有效生长。 还提供了由新型猿猴腺病毒序列和蛋白构成的载体，含有其的宿主细胞及其用途。

    Intelligent controller accessed through addressable virtual space
    40.
    发明授权
    Intelligent controller accessed through addressable virtual space 有权
    智能控制器通过可寻址的虚拟空间进行访问

    公开(公告)号：US07167951B2

    公开(公告)日：2007-01-23

    申请号：US10263274

    申请日：2002-10-02

    申请人： Jerry A. Blades ,  Matthew C. Dewey ,  Bruce A. Thompson ,  David J. Van Maren ,  James M. Wilson

    发明人： Jerry A. Blades ,  Matthew C. Dewey ,  Bruce A. Thompson ,  David J. Van Maren ,  James M. Wilson

    IPC分类号： G06F12/00

    CPC分类号： G06F3/0664 ,  G06F3/0607 ,  G06F3/0643 ,  G06F3/0679 ,  G06F12/08

    摘要： Mass storage system controller apparatus receives requests for access to files in a data storage system and manages access to the files in the data storage system, the data storage system having a plurality of storage devices and the requests being addressed to the data storage system as a single virtual storage device having addressable Command Regions allocated to controller commands and addressable Mapped Data Regions allocated for data storage. The apparatus includes a file system to manage access to files in the data storage system, the file system having a processor acting as a Command Region processor and acting as a Mapped Data Region processor. A disk emulator responds as a disk drive device to write/read commands and passes the write/read commands addressed to Command Regions of the virtual storage device to the Command Region processor, the write/read commands addressed to Command Regions containing controller commands for the file system. The Command Region processor responds to controller commands in the write/read commands and processes the controller commands to control files in the data storage system. The disk emulator responds as a disk drive device to write/read commands and passes write/read commands addressed to a Mapped Data Region of the virtual storage device to the Mapped Data Region processor. The Mapped Data Region processor responds to a write/read command with a Mapped Data Region address and transfers data to or from the data storage system for files mapped to the Mapped Data Region address.

    摘要翻译： 大容量存储系统控制器装置接收访问数据存储系统中的文件的请求，并管理对数据存储系统中的文件的访问，数据存储系统具有多个存储装置，并且请求被作为数据存储系统寻址到数据存储系统 单个虚拟存储设备具有分配给控制器命令的可寻址命令区域和分配用于数据存储的可寻址映射数据区域。 该装置包括用于管理数据存储系统中文件访问的文件系统，该文件系统具有用作命令区域处理器的处理器并用作映射数据区域处理器。 磁盘仿真器作为磁盘驱动器设备作为写入/读取命令进行响应，并将寻址到虚拟存储设备的命令区域的写入/读取命令传递到命令区域处理器，写入/读取命令寻址到包含控制器命令的命令区域 文件系统。 命令区域处理器响应写/读命令中的控制器命令，并处理控制器命令以控制数据存储系统中的文件。 磁盘仿真器作为磁盘驱动器设备进行响应，以写/读命令，并将寻址到虚拟存储设备的映射数据区的写/读命令传递给映射数据区处理器。 映射数据区域处理器使用映射数据区域地址响应写入/读取命令，并将数据传输到数据存储系统或从映射到映射到映射数据区域地址的文件传输数据。