公开(公告)号：EP0787200A2

公开(公告)日：1997-08-06

申请号：EP95942839.0

申请日：1995-10-27

申请人： THE TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA

发明人： WILSON, James, M. ,  FISHER, Krishna, J. ,  CHEN, Shu-Jen ,  WEITZMAN, Matthew

IPC分类号： C12N15 ,  A61K35 ,  A61K48 ,  C12N7

CPC分类号： C12N7/00 ,  A61K48/00 ,  C12N15/86 ,  C12N2710/10343 ,  C12N2810/6018 ,  C12N2840/44

摘要： A recombinant adenovirus and a method for producing the virus are provided which utilize a recombinant shuttle vector comprising adenovirus DNA sequence for the 5' and 3' cis-elements necessary for replication and virion encapsidation in the absence of sequence encoding viral genes and a selected minigene linked thereto, and a helper adenovirus comprising sufficient adenovirus gene sequences necessary for a productive viral infection. Desirably the helper gene is crippled by modifications to its 5' packaging sequences, which facilitates purification of the viral particle from the helper virus.

公开(公告)号：EP0787200B1

公开(公告)日：2005-04-20

申请号：EP95942839.2

申请日：1995-10-27

申请人： THE TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA

发明人： WILSON, James, M. ,  FISHER, Krishna, J. ,  CHEN, Shu-Jen ,  WEITZMAN, Matthew

IPC分类号： C12N15/86 ,  C12N7/00 ,  C12N15/88 ,  A61K48/00

CPC分类号： C12N7/00 ,  A61K48/00 ,  C12N15/86 ,  C12N2710/10343 ,  C12N2810/6018 ,  C12N2840/44

摘要： A recombinant adenovirus and a method for producing the virus are provided which utilize a recombinant shuttle vector comprising adenovirus DNA sequence for the 5' and 3' cis-elements necessary for replication and virion encapsidation in the absence of sequence encoding viral genes and a selected minigene linked thereto, and a helper adenovirus comprising sufficient adenovirus gene sequences necessary for a productive viral infection. Desirably the helper gene is crippled by modifications to its 5' packaging sequences, which facilitates purification of the viral particle from the helper virus.

摘要翻译： 提供重组腺病毒及其制备方法，该方法利用包含腺病毒DNA序列的重组穿梭载体，用于在不存在编码病毒基因的序列和选择的小基因的情况下用于复制和病毒粒子壳化所需的5'和3'顺式元件 和包含足够的用于生产性病毒感染所必需的腺病毒基因序列的辅助性腺病毒。 帮助基因通过修饰其5'包装序列而被削弱，这有助于从辅助病毒纯化病毒颗粒。

公开(公告)号：EP2553106A2

公开(公告)日：2013-02-06

申请号：EP11713419.7

申请日：2011-03-28

申请人： The Trustees Of The University Of Pennsylvania

发明人： WILSON, James, M. ,  CHEN, Shu-Jen ,  TRETIAKOVA, Anna, P.

IPC分类号： C12N15/86 ,  C12N15/864 ,  A61K48/00

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，其设计用于使用使用内置安全机制工程化的复制缺陷病毒组合物将治疗产品递送至受试者，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用于消融转基因或负调节转基因表达的综合方法（本文称为PITA（Pharmacological Induced Transgene Ablation））。 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。