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    Engineered cellular pathways for programmed autoregulation of differentiation
    1.
    发明授权
    Engineered cellular pathways for programmed autoregulation of differentiation 有权
    用于程序自动调节分化的工程化细胞途径

    公开(公告)号：US08685720B2

    公开(公告)日：2014-04-01

    申请号：US12312197

    申请日：2007-11-01

    申请人： Ron Weiss ,  Ihor Lemischka ,  Priscilla E. M. Purnick ,  Christoph Schaniel ,  Miles Miller ,  Patrick Guye

    发明人： Ron Weiss ,  Ihor Lemischka ,  Priscilla E. M. Purnick ,  Christoph Schaniel ,  Miles Miller ,  Patrick Guye

    IPC分类号： C12N15/00 ,  C12N15/09 ,  C12N15/31 ,  C12N15/63

    CPC分类号： C12N15/85 ,  C12N2800/40 ,  C12N2830/002 ,  C12N2830/003 ,  C12N2830/005 ,  C12N2830/006 ,  C12N2830/008 ,  C12N2830/15 ,  C12N2830/55 ,  C12N2830/85

    摘要： The present invention provides compositions and methods for programming mammalian cells to perform desired functions. In particular, the present invention provides compositions and methods for programming stem cells to differentiate into a desired cell type. A quorum sensing systems that regulates the expression of cell fate regulators is introduced into mammalian host cells, such as stem cells. The quorum sensing systems generally comprises vectors that express the components of a bacterial quorum sensing pathway, including proteins which catalyze the synthesis of an autoinducer and a gene encoding a regulatory partner of the autoinducer, and vectors in which genes encoding cell fate regulators are operably linked to a promoter induced by the autoinducer/regulatory partner complex. The system can also comprise vectors in which genes encoding additional cell fate regulators are operably linked to a promoter that is induced by a factor synthesized in response to a first stage of differentiation, so that a second stage of differentiation is triggered.

    摘要翻译： 本发明提供用于编程哺乳动物细胞以实现所需功能的组合物和方法。 特别地，本发明提供了用于编程干细胞以分化成所需细胞类型的组合物和方法。 调节细胞命运调节因子表达的群体感应系统被引入哺乳动物宿主细胞，例如干细胞。 群体感测系统通常包括表达细菌群体感知途径的组分的载体，包括催化自身诱导剂的合成的蛋白质和编码自身诱导剂的调节配偶体的基因以及编码细胞命运调节物的基因可操作地连接的载体 由自动诱导剂/调节配体复合物诱导的启动子。 该系统还可以包含载体，其中编码另外的细胞命运调节子的基因可操作地连接到由响应于第一分化阶段合成的因子诱导的启动子，从而触发第二阶段的分化。

    ENGINEERED CELLULAR PATHWAYS FOR PROGRAMMED AUTOREGULATION OF DIFFERENTIATION
    2.
    发明申请
    ENGINEERED CELLULAR PATHWAYS FOR PROGRAMMED AUTOREGULATION OF DIFFERENTIATION 有权
    用于编程自动分拣的工程细胞路径

    公开(公告)号：US20100285584A1

    公开(公告)日：2010-11-11

    申请号：US12312197

    申请日：2007-11-01

    申请人： Ron Weiss ,  Ihor Lemischka ,  Priscilla Purnick ,  Christoph Schaniel ,  Miles Miller ,  Patrick Guye

    发明人： Ron Weiss ,  Ihor Lemischka ,  Priscilla Purnick ,  Christoph Schaniel ,  Miles Miller ,  Patrick Guye

    IPC分类号： C12N5/071 ,  C12N15/79

    CPC分类号： C12N15/85 ,  C12N2800/40 ,  C12N2830/002 ,  C12N2830/003 ,  C12N2830/005 ,  C12N2830/006 ,  C12N2830/008 ,  C12N2830/15 ,  C12N2830/55 ,  C12N2830/85

    摘要： The present invention provides compositions and methods for programming mammalian cells to perform desired functions. In particular, the present invention provides compositions and methods for programming stem cells to differentiate into a desired cell type. A quorum sensing systems that regulates the expression of cell fate regulators is introduced into mammalian host cells, such as stem cells. The quorum sensing systems generally comprises vectors that express the components of a bacterial quorum sensing pathway, including proteins which catalyze the synthesis of an autoinducer and a gene encoding a regulatory partner of the autoinducer, and vectors in which genes encoding cell fate regulators are operably linked to a promoter induced by the autoinducer/regulatory partner complex. The system can also comprise vectors in which genes encoding additional cell fate regulators are operably linked to a promoter that is induced by a factor synthesized in response to a first stage of differentiation, so that a second stage of differentiation is triggered.

    摘要翻译： 本发明提供用于编程哺乳动物细胞以实现所需功能的组合物和方法。 特别地，本发明提供了用于编程干细胞以分化成所需细胞类型的组合物和方法。 调节细胞命运调节因子表达的群体感应系统被引入哺乳动物宿主细胞，例如干细胞。 群体感测系统通常包括表达细菌群体感知途径的组分的载体，包括催化自身诱导剂的合成的蛋白质和编码自身诱导剂的调节配偶体的基因以及编码细胞命运调节物的基因可操作地连接的载体 由自动诱导剂/调节配体复合物诱导的启动子。 该系统还可以包含载体，其中编码另外的细胞命运调节子的基因可操作地连接到由响应于第一分化阶段合成的因子诱导的启动子，从而触发第二阶段的分化。

    Detection and destruction of cancer cells using programmed genetic vectors
    3.
    发明授权
    Detection and destruction of cancer cells using programmed genetic vectors 有权
    使用编程遗传载体检测和破坏癌细胞

    公开(公告)号：US09458472B2

    公开(公告)日：2016-10-04

    申请号：US12587994

    申请日：2009-10-15

    申请人： Ron Weiss ,  Priscilla E. M. Purnick ,  Caroline DeHart ,  Jon Monk ,  Aparna Swaminathan

    发明人： Ron Weiss ,  Priscilla E. M. Purnick ,  Caroline DeHart ,  Jon Monk ,  Aparna Swaminathan

    IPC分类号： A61K48/00 ,  A61P35/00 ,  C12N15/86 ,  C12N15/63 ,  A61K35/13 ,  C12N15/113

    CPC分类号： C12N15/86 ,  A61K35/13 ,  A61K48/0058 ,  C12N15/113 ,  C12N15/63 ,  C12N2310/14 ,  C12N2740/15043 ,  C12N2840/005 ,  C12N2840/007 ,  C12N2840/102 ,  C12N2840/85 ,  C12N2999/007

    摘要： In its various embodiments, the invention provides, first, a composition comprising a vector for transfecting a cell. The vector comprises a first nucleic acid encoding an antisense agent having thereon an RNA interference target for a transcript of a gene endogenous to the cell. The vector further comprises a second nucleic acid that encodes a cell-killing agent. The second nucleic acid further comprises a sequence of nucleotides transcribable into a non-coding region of a transcript of the second nucleic acid, such that the non-coding region becomes an RNA interference target for the antisense agent. In the transfected cell, the vector operates to interfere with the expression of the cell-killing agent unless and until the vector senses certain endogenous gene signals, whereupon it releases the cell-killing agent. Second, the invention provides a method of treating a disease in a patient by killing cells responsible for the disease, the method comprising administering the vector to the patient until the disease, or a symptom thereof, is ameliorated.

    摘要翻译： 在其各种实施方案中，本发明首先提供包含用于转染细胞的载体的组合物。 载体包含编码其上具有细胞内源性基因的转录物的RNA干扰靶的反义剂的第一核酸。 载体还包含编码细胞杀伤剂的第二核酸。 第二核酸还包含可转录到第二核酸的转录物的非编码区的核苷酸序列，使得非编码区成为反义剂的RNA干扰靶。 在转染的细胞中，载体干扰细胞杀伤剂的表达，除非和直到载体感测到某些内源基因信号，从而释放细胞杀伤剂。 第二，本发明提供了一种通过杀死负责该疾病的细胞来治疗患者疾病的方法，所述方法包括向患者施用该载体，直到疾病或其症状得到改善。