公开(公告)号：US07601823B2

公开(公告)日：2009-10-13

申请号：US11256726

申请日：2005-10-24

申请人： Li Niu ,  Zhen Huang ,  Hua Shi ,  John T. Lis

发明人： Li Niu ,  Zhen Huang ,  Hua Shi ,  John T. Lis

IPC分类号： C07H21/02

CPC分类号： C12N15/115 ,  C12N2310/16

摘要： The present invention relates to novel nucleic acid ligands or aptamers that bind to and inhibit the activation of the α-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) subtype of ionotropic glutamate receptors. Also disclosed is a novel combination of technologies, i.e., SELEX and laser pulse photolysis for the selection and screening of aptamers that inhibit receptor function and are useful therefore, in the treatment of diseases associated with excessive activation of ionotropic glutamate receptors.

摘要翻译： 本发明涉及结合并抑制离子型谷氨酸受体的α-氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA）亚型的活化的新型核酸配体或适体。 还公开了技术的新型组合，即SELEX和激光脉冲光解用于选择和筛选抑制受体功能的适体，因此可用于治疗与离子型谷氨酸受体的过度活化相关的疾病。

公开(公告)号：US20090197271A1

公开(公告)日：2009-08-06

申请号：US12305102

申请日：2007-06-18

申请人： Michael Kotlikoff ,  Hua Shi ,  Bo Shui ,  John T. Lis

发明人： Michael Kotlikoff ,  Hua Shi ,  Bo Shui ,  John T. Lis

IPC分类号： C12Q1/68 ,  C07H21/04 ,  C07K14/435 ,  C12N5/10

CPC分类号： C12Q1/6897 ,  C12N15/111 ,  C12N15/113 ,  C12N2310/14 ,  C12N2310/16 ,  C12N2310/3519 ,  C12N2320/11

摘要： The present invention relates to a nucleic acid aptamer having a first domain that binds to a fluorescent protein. The nucleic acid aptamer forms a molecular complex whereby the aptamer binds a fluorescent protein at the first domain. A constructed DNA molecule, expression systems, and host cells containing the molecular complex are also disclosed. The invention also relates to a system containing a first DNA molecule encoding the nucleic acid aptamer of the present invention and a second DNA molecule encoding a fluorescent protein capable of being bound by the first domain. Methods of detecting a molecular target and determining location of a molecular target using the nucleic acid aptamer of the invention are also disclosed.

摘要翻译： 本发明涉及具有结合荧光蛋白的第一结构域的核酸适体。 核酸适体形​​成分子复合物，由此适体在第一结构域结合荧光蛋白。 还公开了构建的DNA分子，表达系统和含有分子复合物的宿主细胞。 本发明还涉及包含编码本发明的核酸适配体的第一DNA分子和编码能够被第一结构域结合的荧光蛋白的第二DNA分子的系统。 还公开了使用本发明的核酸适体检测分子靶标和确定分子靶位置的方法。

公开(公告)号：US20140371080A1

公开(公告)日：2014-12-18

申请号：US13918927

申请日：2013-06-15

申请人： John T. LIS ,  Abdullah OZER ,  Jacob M. TOME

发明人： John T. LIS ,  Abdullah OZER ,  Jacob M. TOME

IPC分类号： C12Q1/68

CPC分类号： C12Q1/6834 ,  G01N33/5308

摘要： The present invention is directed to a method for detecting an interaction between a ribonucleic acid (RNA) molecule and a second molecule. This method involves providing a nucleic acid construct that contains a promoter sequence, a nucleotide sequence encoding the RNA molecule, and an RNA polymerase blocking site. The nucleotide sequence encoding the RNA molecule is transcribed in vitro to produce an RNA transcript corresponding to the RNA molecule. Transcription is halted by the RNA polymerase blocking site under conditions effective for the RNA transcript to remain tethered to the nucleic acid construct. The tethered RNA transcript is contacted with the second molecule and any interaction between the tethered RNA transcript and the second molecule is detecting and identified based on said contacting.

摘要翻译： 本发明涉及检测核糖核酸（RNA）分子和第二分子之间相互作用的方法。 该方法涉及提供含有启动子序列，编码RNA分子的核苷酸序列和RNA聚合酶阻断位点的核酸构建体。 编码RNA分子的核苷酸序列在体外转录以产生对应于RNA分子的RNA转录物。 在对RNA转录物有效的条件下，RNA聚合酶阻断位点的转录停止在核酸构建体上。 连接的RNA转录物与第二分子接触，并且基于所述接触检测和鉴定系留RNA转录物和第二分子之间的任何相互作用。

公开(公告)号：US20120225929A1

公开(公告)日：2012-09-06

申请号：US13323161

申请日：2011-12-12

申请人： Li NIU ,  Zhen HUANG ,  Hua SHI ,  John T. LIS

发明人： Li NIU ,  Zhen HUANG ,  Hua SHI ,  John T. LIS

IPC分类号： A61K31/7088 ,  C07H21/04 ,  C07H21/02

CPC分类号： C12N15/115 ,  C12N2310/16

摘要： The present invention relates to novel nucleic acid ligands or aptamers that bind to and inhibit the activation of the α-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) subtype of ionotropic glutamate receptors. Also disclosed is a novel combination of technologies, i.e., SELEX and laser pulse photolysis for the selection and screening of aptamers that inhibit receptor function and are useful therefore, in the treatment of diseases associated with excessive activation of ionotropic glutamate receptors.

摘要翻译： 本发明涉及结合并抑制离子型谷氨酸受体的α-氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA）亚型的活化的新型核酸配体或适体。 还公开了技术的新型组合，即SELEX和激光脉冲光解用于选择和筛选抑制受体功能的适体，因此可用于治疗与离子型谷氨酸受体的过度活化相关的疾病。

公开(公告)号：US08076467B2

公开(公告)日：2011-12-13

申请号：US12578231

申请日：2009-10-13

申请人： Li Niu ,  Zhen Huang ,  Hua Shi ,  John T. Lis

发明人： Li Niu ,  Zhen Huang ,  Hua Shi ,  John T. Lis

IPC分类号： C07H21/02 ,  C07H21/04 ,  C40B40/06 ,  C40B40/00 ,  C40B50/00 ,  C40B30/00 ,  A61K48/00

CPC分类号： C12N15/115 ,  C12N2310/16

摘要： The present invention relates to novel nucleic acid ligands or aptamers that bind to and inhibit the activation of the α-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) subtype of ionotropic glutamate receptors. Also disclosed is a novel combination of technologies, i.e., SELEX and laser pulse photolysis for the selection and screening of aptamers that inhibit receptor function and are useful therefore, in the treatment of diseases associated with excessive activation of ionotropic glutamate receptors.

摘要翻译： 本发明涉及结合并抑制离子型谷氨酸受体的α-氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA）亚型的活化的新型核酸配体或适体。 还公开了技术的新型组合，即SELEX和激光脉冲光解用于选择和筛选抑制受体功能的适体，因此可用于治疗与离子型谷氨酸受体的过度活化相关的疾病。

公开(公告)号：US06458559B1

公开(公告)日：2002-10-01

申请号：US09296328

申请日：1999-04-22

申请人： Hua Shi ,  John T. Lis

发明人： Hua Shi ,  John T. Lis

IPC分类号： C12N1563

CPC分类号： C12N15/115 ,  A01K2217/05 ,  C12N2310/111 ,  C12N2310/127 ,  C12N2510/00

摘要： The present invention relates to a monovalent RNA aptamer that binds to Drosophila splicing factor B52 and a multivalent RNA aptamer that includes at least two RNA aptamer sequences linked together. Also disclosed are isolated or constructed DNA molecules which encode either a monovalent RNA aptamer or a multivalent RNA aptamer of the present invention, an engineered gene encoding a multivalent RNA aptamer of the present invention, and host cells and expression systems which contain either a heterologous DNA molecule or a heterologous gene of the present invention. Further aspects of the present invention relate to a method of expressing a multivalent RNA aptamer in a cell, a method of increasing activity of a splicing factor protein in a cell, and a method of inhibiting activity of a target molecule in a cell. A transgenic non-human organism whose somatic and germ cell lines contain an engineered gene encoding a multivalent RNA aptamer is also disclosed.

摘要翻译： 本发明涉及结合果蝇剪接因子B52的单价RNA适配体和包含连接在一起的至少两个RNA适体序列的多价RNA适体。 还公开了分离或构建的DNA分子，其编码本发明的单价RNA适体或多价RNA适体，编码本发明的多价RNA适体的工程化基因，以及含有异源DNA的宿主细胞和表达系统 分子或异源基因。 本发明的另外方面涉及在细胞中表达多价RNA适体的方法，增加细胞中剪接因子蛋白的活性的方法以及抑制细胞中靶分子活性的方法。 还公开了体细胞和生殖细胞系含有编码多价RNA适体的工程化基因的转基因非人生物体。

公开(公告)号：US09938567B2

公开(公告)日：2018-04-10

申请号：US13918927

申请日：2013-06-15

申请人： John T. Lis ,  Abdullah Ozer ,  Jacob M. Tome

发明人： John T. Lis ,  Abdullah Ozer ,  Jacob M. Tome

IPC分类号： G01N33/543 ,  C12Q1/68 ,  G01N33/53

CPC分类号： C12Q1/6834 ,  G01N33/5308

摘要： The present invention is directed to a method for detecting an interaction between a ribonucleic acid (RNA) molecule and a second molecule. This method involves providing a nucleic acid construct that contains a promoter sequence, a nucleotide sequence encoding the RNA molecule, and an RNA polymerase blocking site. The nucleotide sequence encoding the RNA molecule is transcribed in vitro to produce an RNA transcript corresponding to the RNA molecule. Transcription is halted by the RNA polymerase blocking site under conditions effective for the RNA transcript to remain tethered to the nucleic acid construct. The tethered RNA transcript is contacted with the second molecule and any interaction between the tethered RNA transcript and the second molecule is detecting and identified based on said contacting.

公开(公告)号：US20120028811A1

公开(公告)日：2012-02-02

申请号：US13059223

申请日：2009-08-17

申请人： Harold G. Craighead ,  John T. Lis ,  Seungmin Park ,  So Youn Kim ,  Jiyoung Ahn ,  Minjoung Jo

发明人： Harold G. Craighead ,  John T. Lis ,  Seungmin Park ,  So Youn Kim ,  Jiyoung Ahn ,  Minjoung Jo

IPC分类号： C40B10/00 ,  C07H21/00 ,  B32B37/14 ,  G03F7/20 ,  B32B37/02 ,  C40B60/08 ,  C40B40/06

CPC分类号： C12Q1/6811 ,  B01L3/502707 ,  B01L3/502715 ,  B01L3/502753 ,  B01L7/52 ,  B01L2200/10 ,  B01L2300/069 ,  B01L2300/0816 ,  B01L2300/0861 ,  B01L2300/0883 ,  B01L2300/1827 ,  B01L2400/0487 ,  C12Q1/686 ,  C12Q2525/205 ,  Y10T156/10 ,  C12Q2565/629 ,  C12Q2541/101

摘要： The present invention relates to microfluidic chips and their use in SELEX. The microfluidic chip preferably includes a reaction chamber that contains a high surface area material that contains target. One preferred high surface area material is a sol-gel derived material. Methods of making the microfluidic chips are described herein, as are uses of these devices to select aptamers against the target.

摘要翻译： 本发明涉及微流控芯片及其在SELEX中的应用。 微流体芯片优选包括含有包含靶的高表面积材料的反应室。 一种优选的高表面积材料是溶胶 - 凝胶衍生材料。 这里描述了制造微流体芯片的方法，以及这些装置用于选择针对靶的适体的方法。

公开(公告)号：US07435542B2

公开(公告)日：2008-10-14

申请号：US10602837

申请日：2003-06-24

申请人： Hua Shi ,  John T. Lis

发明人： Hua Shi ,  John T. Lis

IPC分类号： C12Q1/68 ,  C12P19/34

CPC分类号： C12N15/115 ,  C12N15/1048 ,  C12N15/111 ,  C12N2310/16 ,  C12N2320/13 ,  C12Q1/6811 ,  C12Q2537/161 ,  C12Q2521/301

摘要： A method of identifying RNA ligands which bind to a target molecule by treating a first pool of RNA ligands that collectively bind more than one target under conditions effective to reduce the concentration or eliminate the presence of one or more predominate target-binding RNA ligands from the first pool of RNA ligands; amplifying the RNA ligands in the treated first pool, thereby forming a second pool of RNA ligands that is enriched in one or more non-predominate target-binding RNA ligands of the first pool but not the one or more predominate target-binding RNA ligands thereof; and identifying one or more predominate target-binding RNA ligands that are present in the second pool at a higher concentration than other target-binding RNA ligands. Oligonucleotides and kits which can be used in practicing the present invention are also disclosed, as are aptamers that bind to a heat shock factor protein and their use.

摘要翻译： 通过在有效降低浓度或消除一种或多种主要的靶结合RNA配体的存在的条件下，通过处理共同结合多于一种靶的RNA配体的第一池来鉴定与靶分子结合的RNA配体的方法 第一个RNA配体库; 扩增经处理的第一库中的RNA配体，由此形成富集第一个池中一个或多个非主要的靶结合RNA配体的第二个RNA配体池，但不是一个或多个主要的靶结合RNA配体 ; 并且以比其它靶结合RNA配体更高的浓度鉴定存在于第二池中的一种或多种主要的靶结合RNA配体。 还可以公开可用于实施本发明的寡核苷酸和试剂盒，以及结合热休克因子蛋白的适体及其用途。

公开(公告)号：US20100099749A1

公开(公告)日：2010-04-22

申请号：US12578231

申请日：2009-10-13

申请人： Li NIU ,  Zhen HUANG ,  Hua SHI ,  John T. LIS

发明人： Li NIU ,  Zhen HUANG ,  Hua SHI ,  John T. LIS

IPC分类号： A61K31/7088 ,  C07H21/04 ,  C12N5/00 ,  C12P19/34 ,  A61P25/00

CPC分类号： C12N15/115 ,  C12N2310/16

摘要： The present invention relates to novel nucleic acid ligands or aptamers that bind to and inhibit the activation of the α-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) subtype of ionotropic glutamate receptors. Also disclosed is a novel combination of technologies, i.e., SELEX and laser pulse photolysis for the selection and screening of aptamers that inhibit receptor function and are useful therefore, in the treatment of diseases associated with excessive activation of ionotropic glutamate receptors.

摘要翻译： 本发明涉及结合并抑制离子型谷氨酸受体的α-氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA）亚型的活化的新型核酸配体或适体。 还公开了技术的新型组合，即SELEX和激光脉冲光解用于选择和筛选抑制受体功能的适体，因此可用于治疗与离子型谷氨酸受体的过度活化相关的疾病。