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。

公开(公告)号：US20110150854A1

公开(公告)日：2011-06-23

申请号：US13033352

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： A61K31/714 ,  A61K38/43 ,  A61K31/675 ,  A61P31/00

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.

公开(公告)号：US20100190244A1

公开(公告)日：2010-07-29

申请号：US12709072

申请日：2010-02-19

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： C12N15/63 ,  C07H21/02

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交换（或以其他方式修饰） 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。

公开(公告)号：US20100184810A1

公开(公告)日：2010-07-22

申请号：US12532477

申请日：2008-03-24

申请人： Ronald R. Breaker ,  Ming Tatt Cheah ,  Narasimhan Sudarsan ,  Andreas Wachter

发明人： Ronald R. Breaker ,  Ming Tatt Cheah ,  Narasimhan Sudarsan ,  Andreas Wachter

IPC分类号： A61K31/4439 ,  C12N15/74 ,  A61K31/44 ,  A61K31/4427 ,  A61K31/443 ,  A61K31/4436 ,  A61P31/10

CPC分类号： C12N15/111 ,  C12N15/115 ,  C12N15/63 ,  C12N2310/16 ,  C12N2310/3519 ,  C12N2320/33

摘要： Disclosed are methods and compositions related to riboswitches that control alternative splicing.

摘要翻译： 公开了与控制可变剪接的核糖开关相关的方法和组合物。

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。

公开(公告)号：US20110152213A1

公开(公告)日：2011-06-23

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： A61K31/708 ,  A61K31/522 ,  A61K31/52 ,  A61K31/195 ,  A61K31/132 ,  A61K31/16 ,  A61K31/506 ,  A61P43/00 ,  C12N1/20 ,  C12N1/14 ,  C12N5/04

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.

公开(公告)号：US20100286082A1

公开(公告)日：2010-11-11

申请号：US12602338

申请日：2008-05-29

申请人： Ronald R. Breaker ,  Zasha Weinberg ,  Narasimhan Sudarsan ,  Joy Xin Wang ,  Michelle M. Meyer ,  Adam Roth ,  Elizabeth E. Regulski

发明人： Ronald R. Breaker ,  Zasha Weinberg ,  Narasimhan Sudarsan ,  Joy Xin Wang ,  Michelle M. Meyer ,  Adam Roth ,  Elizabeth E. Regulski

IPC分类号： A61K31/7076 ,  C07H21/02 ,  C12Q1/68 ,  C12N1/20 ,  A01N43/54 ,  A61P31/04 ,  A01P1/00

CPC分类号： C12N15/67

摘要： Riboswitches are targets for antibiotics and other small molecule therapies. Riboswitches and portions thereof can be used to regulate the expression or function of RNA molecules and other elements and molecules. Riboswitches and portions thereof can be used in a variety of other methods to, for example, identify or detect compounds. Compounds can be used to stimulate, active, inhibit and/or inactivate the riboswitch. Riboswitches and portions thereof, both alone and in combination with other nucleic acids, can be used in a variety of constructs and RNA molecules and can be encoded by nucleic acids.

摘要翻译： 核糖开关是抗生素和其他小分子治疗的靶标。 核糖开关及其部分可用于调节RNA分子和其他元件和分子的表达或功能。 核糖开关及其部分可用于各种其它方法中以例如鉴定或检测化合物。 化合物可用于刺激，活化，抑制和/或灭活核糖开关。 单独和与其他核酸组合的核糖开关及其部分可用于多种构建体和RNA分子中并且可以由核酸编码。

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。

公开(公告)号：US20130143955A1

公开(公告)日：2013-06-06

申请号：US13816088

申请日：2011-08-09

申请人： Ronald R. Breaker ,  Jenny Baker ,  Elaine Lee ,  Narasimhan Sudarsan ,  Zasha Weinberg

发明人： Ronald R. Breaker ,  Jenny Baker ,  Elaine Lee ,  Narasimhan Sudarsan ,  Zasha Weinberg

IPC分类号： A01N57/16 ,  A61K48/00 ,  A61K31/7084 ,  C07H21/04 ,  A61K38/16 ,  C12N15/72

CPC分类号： A01N57/16 ,  A61K31/7084 ,  C12N15/113 ,  C12N15/115 ,  C12N2310/12 ,  C12N2310/16 ,  C12N2310/3519 ,  C12N2840/10 ,  C12N2840/44 ,  C12N2840/55 ,  G01N2500/00

摘要： Disclosed are compositions and methods involving cyclic di-GMP—responsive Riboswitches and cyclic di-GMP-II motifs.

摘要翻译： 公开了涉及环状二-GMP反应性Riboswitches和环状二-GMP-II基序的组合物和方法。

公开(公告)号：US20110151471A1

公开(公告)日：2011-06-23

申请号：US13033258

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

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.