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    Compositions and methods for transient expression of recombinant RNA
    2.
    发明授权
    Compositions and methods for transient expression of recombinant RNA 有权

    公开(公告)号：US09951349B2

    公开(公告)日：2018-04-24

    申请号：US14343817

    申请日：2012-09-27

    申请人： Yale University

    发明人： Peter M. Rabinovich ,  Sherman M. Weissman

    IPC分类号： C12N15/85 ,  C12N15/86

    CPC分类号： C12N15/85 ,  C12N15/86 ,  C12N2760/18843 ,  C12N2760/18852

    摘要： Compositions for transient but prolonged exogenous mRNA expression through the use of the transcription system of negative strand RNA viruses, and methods of use thereof are disclosed. In some embodiments, the system contains only RNAs and does not include any DNA molecules. The compositions typically include an RNA template unit (rTeUn) that includes a virus regulatory sequences operably linked to a coding sequence of interest. The rTeUn is typically transfected to a host cell's cytoplasm in the presence of virus expression system proteins that mediate replication of the rTeUn and transcription of the transgene. The rTeUn RNA bonded to viral proteins exhibits high resistance to degradation, prolonged duration of expression, and is free of viral genes. The compositions can be used to reprogram cell. For example, the compositions and methods can be used to redirected lymphocytes to target cancer cells, or to dedifferentiate somatic cells into induce pluripotent stem cells.

    Compositions and Methods for Transient Expression of Recombinant RNA
    5.
    发明申请
    Compositions and Methods for Transient Expression of Recombinant RNA 有权
    用于重组RNA瞬时表达的组合物和方法

    公开(公告)号：US20140249212A1

    公开(公告)日：2014-09-04

    申请号：US14343817

    申请日：2012-09-27

    申请人： Yale University

    发明人： Peter M. Rabinovich ,  Sherman M. Weissman

    IPC分类号： C12N15/85

    CPC分类号： C12N15/85 ,  C12N15/86 ,  C12N2760/18843 ,  C12N2760/18852

    摘要： Compositions for transient but prolonged exogenous mRNA expression through the use of the transcription system of negative strand RNA viruses, and methods of use thereof are disclosed. In some embodiments, the system contains only RNAs and does not include any DNA molecules. The compositions typically include an RNA template unit (rTeUn) that includes a virus regulatory sequences operably linked to a coding sequence of interest. The rTeUn is typically transfected to a host cell's cytoplasm in the presence of virus expression system proteins that mediate replication of the rTeUn and transcription of the transgene. The rTeUn RNA bonded to viral proteins exhibits high resistance to degradation, prolonged duration of expression, and is free of viral genes. The compositions can be used to reprogram cell. For example, the compositions and methods can be used to redirected lymphocytes to target cancer cells, or to dedifferentiate somatic cells into induce pluripotent stem cells.

    摘要翻译： 公开了通过使用负链RNA病毒的转录系统的瞬时但延长的外源mRNA表达的组合物及其使用方法。 在一些实施方案中，系统仅含有RNA并且不包括任何DNA分子。 组合物通常包括RNA模板单元（rTeUn），其包含与感兴趣的编码序列可操作地连接的病毒调节序列。 在介导rTeUn复制和转录转录的病毒表达系统蛋白的存在下，rTeUn通常被转染至宿主细胞的细胞质。 与病毒蛋白结合的rTeUn RNA表现出高度的降解抗性，延长的表达持续时间，并且没有病毒基因。 组合物可用于重新编程细胞。 例如，组合物和方法可用于将淋巴细胞重定向至靶癌细胞，或将体细胞去分化为诱导多能干细胞。

    METHOD FOR EXPRESSION OF HETEROLOGOUS PROTEINS USING A RECOMBINANT NEGATIVE-STRAND RNA VIRUS VECTOR
    9.
    发明申请
    METHOD FOR EXPRESSION OF HETEROLOGOUS PROTEINS USING A RECOMBINANT NEGATIVE-STRAND RNA VIRUS VECTOR 审中-公开
    使用重组负反馈RNA病毒载体表达异位蛋白的方法

    公开(公告)号：US20150133531A1

    公开(公告)日：2015-05-14

    申请号：US14404109

    申请日：2013-05-24

    申请人： AmVac AG

    发明人： Marian Wiegand

    IPC分类号： C12N15/86 ,  C07K14/47 ,  C12N7/00

    CPC分类号： C12N15/86 ,  A61K48/00 ,  C07K14/4702 ,  C12N5/0696 ,  C12N7/00 ,  C12N2760/18822 ,  C12N2760/18843 ,  C12N2760/18852 ,  C12N2760/18862 ,  C12N2800/24

    摘要： The present invention provides a method of expressing at least one heterologous nucleic acid sequence in a cell, the method comprising introducing at least one heterologous nucleic acid sequence into a cell by infecting said cell with a recombinant negative-strand RNA virus vector comprising said at least one heterologous nucleic acid sequence, wherein the recombinant negative-strand RNA virus vector includes a viral genome coding for a mutated P protein, which leads to a loss of the viral genome replication ability without a loss of the viral transcription ability, and wherein said at least one heterologous nucleic acid sequence encodes a cellular reprogramming or programming factor or a therapeutic protein. In addition, the present invention provides a cell or a population of cells prepared in vitro by said method as well as a pharmaceutical composition comprising said cell or population of cells.

    摘要翻译： 本发明提供了在细胞中表达至少一种异源核酸序列的方法，所述方法包括通过用重组负链RNA病毒载体感染所述细胞将至少一种异源核酸序列引入细胞，所述重组负链RNA病毒载体包含至少 一种异源核酸序列，其中重组负链RNA病毒载体包括编码突变的P蛋白的病毒基因组，其导致病毒基因组复制能力的丧失而不损失病毒转录能力，并且其中所述 至少一个异源核酸序列编码细胞重编程或编程因子或治疗性蛋白质。 此外，本发明提供了通过所述方法体外制备的细胞或细胞群以及包含所述细胞或细胞群的药物组合物。