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    Riboswitches, methods for their use, and compositions for use with riboswitches
    1.
    发明授权
    Riboswitches, methods for their use, and compositions for use with riboswitches 有权
    核糖开关，其使用方法和用于核糖开关的组合物

    公开(公告)号：US07794931B2

    公开(公告)日：2010-09-14

    申请号：US10669162

    申请日：2003-09-22

    申请人： Ronald R. Breaker ,  Ali Nahvi ,  Narasimhan Sudarsan ,  Margaret S. Ebert ,  Wade Winkler ,  Jeffrey E. Barrick ,  John K. Wickiser

    发明人： Ronald R. Breaker ,  Ali Nahvi ,  Narasimhan Sudarsan ,  Margaret S. Ebert ,  Wade Winkler ,  Jeffrey E. Barrick ,  John K. Wickiser

    IPC分类号： C12Q1/68 ,  C12P19/34 ,  C07H21/02 ,  C07H21/04

    CPC分类号： C12N15/113 ,  A61K31/00 ,  C07D415/00 ,  C07D473/18 ,  C07D473/34 ,  C12N15/115 ,  C12N15/67 ,  C12N2310/53

    摘要： It has been discovered that certain natural mRNAs serve as metabolite-sensitive genetic switches wherein the RNA directly binds a small organic molecule. This binding process changes the conformation of the mRNA, which causes a change in gene expression by a variety of different mechanisms. Modified versions of these natural “riboswitches” (created by using various nucleic acid engineering strategies) can be employed as designer genetic switches that are controlled by specific effector compounds. Such effector compounds that activate a riboswitch are referred to herein as trigger molecules. The natural switches are targets for antibiotics and other small molecule therapies. In addition, the architecture of riboswitches allows actual pieces of the natural switches to be used to construct new non-immunogenic genetic control elements, for example the aptamer (molecular recognition) domain can be swapped with other non-natural aptamers (or otherwise modified) such that the new recognition domain causes genetic modulation with user-defined effector compounds. The changed switches become part of a therapy regimen—turning on, or off, or regulating protein synthesis. Newly constructed genetic regulation networks can be applied in such areas as living biosensors, metabolic engineering of organisms, and in advanced forms of gene therapy treatments.

    摘要翻译： 已经发现某些天然mRNA用作代谢物敏感的遗传开关，其中RNA直接结合小的有机分子。 这种结合过程改变mRNA的构象，其通过各种不同的机制引起基因表达的改变。 这些天然“核糖开关”（通过使用各种核酸工程策略产生）的修饰版本可被用作由特异性效应子化合物控制的设计者遗传开关。 激活核糖开关的这种效应子化合物在本文中称为触发分子。 天然开关是抗生素和其他小分子治疗的靶标。 此外，核糖开关的结构允许使用自然开关的实际部分来构建新的非免疫原性遗传控制元件，例如适配子（分子识别）结构域可以与其他非天然适体（或以其它方式修饰）交换， 使得新的识别域引起用户定义的效应子化合物的遗传调节。 改变的开关成为治疗方案的一部分 - 打开或关闭或调节蛋白质合成。 新建的遗传调控网络可以应用于生物传感器，生物体的代谢工程和基因治疗治疗的先进形式等领域。

    RIBOSWITCHES, METHODS FOR THEIR USE, AND COMPOSITIONS FOR USE WITH RIBOSWITCHES
    3.
    发明申请
    RIBOSWITCHES, METHODS FOR THEIR USE, AND COMPOSITIONS FOR USE WITH RIBOSWITCHES 审中-公开
    RIBOSWITCHES，其使用方法和使用RIBOSWITCHES的组合物

    公开(公告)号：US20110152215A1

    公开(公告)日：2011-06-23

    申请号：US13033319

    申请日：2011-02-23

    申请人： Ronald R. Breaker ,  Ali Nahvi ,  Narasimhan Sudarsan ,  Margaret S. Ebert ,  Wade Winkler ,  Jeffrey E. Barrick ,  John K. Wickiser

    发明人： Ronald R. Breaker ,  Ali Nahvi ,  Narasimhan Sudarsan ,  Margaret S. Ebert ,  Wade Winkler ,  Jeffrey E. Barrick ,  John K. Wickiser

    IPC分类号： A61K31/7076 ,  A61K31/522 ,  A61K31/52 ,  A61K31/198 ,  A61K31/51 ,  A61K31/675 ,  C12N1/20 ,  A61P43/00 ,  G01N33/53

    CPC分类号： C12N15/113 ,  A61K31/00 ,  C07D415/00 ,  C07D473/18 ,  C07D473/34 ,  C12N15/115 ,  C12N15/67 ,  C12N2310/53

    摘要： It has been discovered that certain natural mRNAs serve as metabolite-sensitive genetic switches wherein the RNA directly binds a small organic molecule. This binding process changes the conformation of the mRNA, which causes a change in gene expression by a variety of different mechanisms. Modified versions of these natural “riboswitches” (created by using various nucleic acid engineering strategies) can be employed as designer genetic switches that are controlled by specific effector compounds. Such effector compounds that activate a riboswitch are referred to herein as trigger molecules. The natural switches are targets for antibiotics and other small molecule therapies. In addition, the architecture of riboswitches allows actual pieces of the natural switches to be used to construct new non-immunogenic genetic control elements, for example the aptamer (molecular recognition) domain can be swapped with other non-natural aptamers (or otherwise modified) such that the new recognition domain causes genetic modulation with user-defined effector compounds. The changed switches become part of a therapy regimen—turning on, or off, or regulating protein synthesis. Newly constructed genetic regulation networks can be applied in such areas as living biosensors, metabolic engineering of organisms, and in advanced forms of gene therapy treatments.

    摘要翻译： 已经发现某些天然mRNA用作代谢物敏感的遗传开关，其中RNA直接结合小的有机分子。 这种结合过程改变mRNA的构象，其通过各种不同的机制引起基因表达的改变。 这些天然“核糖开关”（通过使用各种核酸工程策略产生）的修饰版本可被用作由特异性效应子化合物控制的设计者遗传开关。 激活核糖开关的这种效应子化合物在本文中称为触发分子。 天然开关是抗生素和其他小分子治疗的靶标。 此外，核糖开关的结构允许使用自然开关的实际部分来构建新的非免疫原性遗传控制元件，例如适配子（分子识别）结构域可以与其他非天然适体（或以其它方式修饰）交换， 使得新的识别域引起用户定义的效应子化合物的遗传调节。 改变的开关成为治疗方案的一部分 - 打开或关闭或调节蛋白质合成。 新建的遗传调控网络可以应用于生物传感器，生物体的代谢工程和基因治疗治疗的先进形式等领域。

    Riboswitches, methods for their use, and compositions for use with riboswitches
    5.
    发明授权
    Riboswitches, methods for their use, and compositions for use with riboswitches 有权
    核糖开关，其使用方法和用于核糖开关的组合物

    公开(公告)号：US08440810B2

    公开(公告)日：2013-05-14

    申请号：US13033174

    申请日：2011-02-23

    申请人： Ronald R. Breaker ,  Ali Nahvi ,  Narasimhan Sudarsan ,  Margaret S. Ebert ,  Wade Winkler ,  Jeffrey E. Barrick ,  John K. Wickiser

    发明人： Ronald R. Breaker ,  Ali Nahvi ,  Narasimhan Sudarsan ,  Margaret S. Ebert ,  Wade Winkler ,  Jeffrey E. Barrick ,  John K. Wickiser

    IPC分类号： C12Q1/68 ,  C12P19/34 ,  C12N15/63 ,  C07H21/02 ,  C07H21/04

    CPC分类号： C12N15/113 ,  A61K31/00 ,  C07D415/00 ,  C07D473/18 ,  C07D473/34 ,  C12N15/115 ,  C12N15/67 ,  C12N2310/53

    摘要： It has been discovered that certain natural mRNAs serve as metabolite-sensitive genetic switches wherein the RNA directly binds a small organic molecule. This binding process changes the conformation of the mRNA, which causes a change in gene expression by a variety of different mechanisms. Modified versions of these natural “riboswitches” (created by using various nucleic acid engineering strategies) can be employed as designer genetic switches that are controlled by specific effector compounds. Such effector compounds that activate a riboswitch are referred to herein as trigger molecules. The natural switches are targets for antibiotics and other small molecule therapies. In addition, the architecture of riboswitches allows actual pieces of the natural switches to be used to construct new non-immunogenic genetic control elements, for example the aptamer (molecular recognition) domain can be swapped with other non-natural aptamers (or otherwise modified) such that the new recognition domain causes genetic modulation with user-defined effector compounds. The changed switches become part of a therapy regimen—turning on, or off, or regulating protein synthesis. Newly constructed genetic regulation networks can be applied in such areas as living biosensors, metabolic engineering of organisms, and in advanced forms of gene therapy treatments.

    摘要翻译： 已经发现某些天然mRNA用作代谢物敏感的遗传开关，其中RNA直接结合小的有机分子。 这种结合过程改变mRNA的构象，其通过各种不同的机制引起基因表达的改变。 这些天然“核糖开关”（通过使用各种核酸工程策略产生）的修饰版本可被用作由特异性效应子化合物控制的设计者遗传开关。 激活核糖开关的这种效应子化合物在本文中称为触发分子。 天然开关是抗生素和其他小分子治疗的靶标。 此外，核糖开关的结构允许使用自然开关的实际部分来构建新的非免疫原性遗传控制元件，例如适配子（分子识别）结构域可以与其他非天然适体（或以其它方式修饰）交换， 使得新的识别域引起用户定义的效应子化合物的遗传调节。 改变的开关成为治疗方案的一部分 - 打开或关闭或调节蛋白质合成。 新建的遗传调控网络可以应用于生物传感器，生物体的代谢工程和基因治疗治疗的先进形式等领域。

    RIBOSWITCHES, METHODS FOR THEIR USE, AND COMPOSITIONS FOR USE WITH RIBOSWITCHES
    7.
    发明申请
    RIBOSWITCHES, METHODS FOR THEIR USE, AND COMPOSITIONS FOR USE WITH RIBOSWITCHES 审中-公开
    RIBOSWITCHES，其使用方法和使用RIBOSWITCHES的组合物

    公开(公告)号：US20100041742A1

    公开(公告)日：2010-02-18

    申请号：US12492866

    申请日：2009-06-26

    申请人： Ronald R. Breaker ,  Ali Nahvi ,  Narasimhan Sudarsan ,  Margaret S. Ebert ,  Wade Winkler ,  Jeffrey E. Barrick ,  John K. Wickiser

    发明人： Ronald R. Breaker ,  Ali Nahvi ,  Narasimhan Sudarsan ,  Margaret S. Ebert ,  Wade Winkler ,  Jeffrey E. Barrick ,  John K. Wickiser

    IPC分类号： A61K31/7088 ,  C12Q1/68 ,  C12N5/00 ,  A61K31/70 ,  A61K31/51 ,  A61K31/195

    CPC分类号： C12N15/113 ,  A61K31/00 ,  C07D415/00 ,  C07D473/18 ,  C07D473/34 ,  C12N15/115 ,  C12N15/67 ,  C12N2310/53

    摘要： It has been discovered that certain natural mRNAs serve as metabolite-sensitive genetic switches wherein the RNA directly binds a small organic molecule. This binding process changes the conformation of the mRNA, which causes a change in gene expression by a variety of different mechanisms. Modified versions of these natural “riboswitches” (created by using various nucleic acid engineering strategies) can be employed as designer genetic switches that are controlled by specific effector compounds. Such effector compounds that activate a riboswitch are referred to herein as trigger molecules. The natural switches are targets for antibiotics and other small molecule therapies. In addition, the architecture of riboswitches allows actual pieces of the natural switches to be used to construct new non-immunogenic genetic control elements, for example the aptamer (molecular recognition) domain can be swapped with other non-natural aptamers (or otherwise modified) such that the new recognition domain causes genetic modulation with user-defined effector compounds. The changed switches become part of a therapy regimen-turning on, or off, or regulating protein synthesis. Newly constructed genetic regulation networks can be applied in such areas as living biosensors, metabolic engineering of organisms, and in advanced forms of gene therapy treatments.

    摘要翻译： 已经发现某些天然mRNA用作代谢物敏感的遗传开关，其中RNA直接结合小的有机分子。 这种结合过程改变mRNA的构象，其通过各种不同的机制引起基因表达的改变。 这些天然“核糖开关”（通过使用各种核酸工程策略产生）的修饰版本可被用作由特异性效应子化合物控制的设计者遗传开关。 激活核糖开关的这种效应子化合物在本文中称为触发分子。 天然开关是抗生素和其他小分子治疗的靶标。 此外，核糖开关的结构允许使用自然开关的实际部分来构建新的非免疫原性遗传控制元件，例如适配子（分子识别）结构域可以与其他非天然适体（或以其它方式修饰）交换， 使得新的识别域引起用户定义的效应子化合物的遗传调节。 改变的开关成为治疗方案的一部分 - 打开或关闭或调节蛋白质合成。 新建的遗传调控网络可以应用于生物传感器，生物体的代谢工程和基因治疗治疗的先进形式等领域。