公开(公告)号：US06706482B2

公开(公告)日：2004-03-16

申请号：US10331083

申请日：2002-12-27

申请人： Jonathan Drew Smith ,  Larry Gold

发明人： Jonathan Drew Smith ,  Larry Gold

IPC分类号： C12Q168

CPC分类号： C12N15/1048

摘要： The invention provides method for producing nucleic acid ligands that generate a signal, or cause a decrease in the level of a signal, in the presence of a target molecule or an environmental stimulus. The methods of the instant invention are collectively termed Conditional SELEX. The nucleic acid ligands of the instant invention are useful in any application where it is desirable to measure the concentration of a target molecule or detect and quantitate an environmental stimulus.

摘要翻译： 本发明提供了在目标分子或环境刺激的存在下产生产生信号或引起信号水平降低的核酸配体的方法。 本发明的方法被统称为条件SELEX。 本发明的核酸配体可用于需要测量靶分子的浓度或检测和定量环境刺激的任何应用中。

公开(公告)号：US06506887B1

公开(公告)日：2003-01-14

申请号：US09364541

申请日：1999-07-29

申请人： Jonathan Drew Smith ,  Larry Gold

发明人： Jonathan Drew Smith ,  Larry Gold

IPC分类号： C07H2102

CPC分类号： C12N15/1048

摘要： The invention provides method for producing nucleic acid ligands that generate a signal, or cause a decrease in the level of a signal, in the presence of a target molecule or an environmental stimulus. The methods of the instant invention are collectively termed Conditional SELEX. The nucleic acid ligands of the instant invention are useful in any application where it is desirable to measure the concentration of a target molecule or detect and quantitate an environmental stimulus.

摘要翻译： 本发明提供了在目标分子或环境刺激的存在下产生产生信号或引起信号水平降低的核酸配体的方法。 本发明的方法被统称为条件SELEX。 本发明的核酸配体可用于需要测量靶分子的浓度或检测和定量环境刺激的任何应用中。

公开(公告)号：US20090286232A1

公开(公告)日：2009-11-19

申请号：US12476796

申请日：2009-06-02

申请人： Jonathan Drew Smith ,  Breanna Leigh Dreiling ,  Breanna Christine Smith ,  John H. Wheeler

发明人： Jonathan Drew Smith ,  Breanna Leigh Dreiling ,  Breanna Christine Smith ,  John H. Wheeler

IPC分类号： C12Q1/70

CPC分类号： C12Q1/04 ,  G01N33/54326 ,  G01N33/56911

摘要： A method of determining the presence or absence of a target microorganism in a sample to be tested, the method comprising: (a) combining with the sample an amount of bacteriophage capable of attaching to the target microorganism to create a bacteriophage-exposed sample; (b) providing conditions to the bacteriophage-exposed sample sufficient to allow the bacteriophage to attach to the target microorganism while inhibiting phage replication in a potentially cross-reactive, non-target microorganism; and (c) assaying the bacteriophage-exposed sample to detect the presence or absence of a bacteriophage marker to determine the presence or absence of the target microorganism; wherein the amount of the bacteriophage is between 10% to 70% of the threshold number of bacteriophage that the assay can detect, or between 1×106pfu/mL and 7×106pfu/mL.

摘要翻译： 一种确定待测试样品中目标微生物的存在或不存在的方法，所述方法包括：（a）与样品结合能够附着于靶微生物以产生噬菌体暴露样品的噬菌体数量; （b）向噬菌体暴露的样品提供足以允许噬菌体附着于靶微生物同时抑制潜在交叉反应性非目标微生物中的噬菌体复制的条件; 和（c）测定噬菌体暴露的样品以检测噬菌体标志物的存在或不存在以确定靶微生物的存在或不存在; 其中所述噬菌体的量为所述测定可检测的噬菌体阈值的10％至70％，或1×10 6 pfu / mL至7×10 6 pfu / mL之间。

公开(公告)号：US06730482B2

公开(公告)日：2004-05-04

申请号：US10096641

申请日：2002-03-12

申请人： Larry Gold ,  Dominic A. Zichi ,  Jonathan Drew Smith

发明人： Larry Gold ,  Dominic A. Zichi ,  Jonathan Drew Smith

IPC分类号： C12Q168

CPC分类号： C12N15/1048 ,  C12Q1/6811 ,  C12Q2523/313

摘要： This invention is directed towards a method for obtaining nucleic acid ligands against target proteins without directly purifying the target proteins. The method used in the invention is called SELEX, which is an acronym for Systematic Evolution of Ligands by EXponential enrichment. The nucleic acid ligands of the invention are useful as diagnostic and therapeutic agents for diseases in which the targets proteins play a causative role.

摘要翻译： 本发明涉及一种在不直接纯化靶蛋白的情况下获得针对靶蛋白的核酸配体的方法。 本发明中使用的方法称为SELEX，它是通过扩充浓缩的配体的系统演化的缩写。 本发明的核酸配体可用作靶蛋白起作用的疾病的诊断和治疗剂。

公开(公告)号：US06387620B1

公开(公告)日：2002-05-14

申请号：US09362578

申请日：1999-07-28

申请人： Jonathan Drew Smith ,  Larry Gold

发明人： Jonathan Drew Smith ,  Larry Gold

IPC分类号： C12Q168

CPC分类号： C12Q1/6811 ,  C12Q2537/155 ,  C12Q2531/113 ,  C12Q2521/501

摘要： Methods are provided for the production of nucleic acid ligands against target molecules using a procedure known as Transcription-free Systematic Evolution of Ligands by EXponential enrichment (Transcription-free SELEX). The Transcription-free SELEX method assembles nucleic acid ligands from fragments of synthetic nucleic acids by annealing those fragments to a complementary template, and then ligating the fragments together.

摘要翻译： 提供了使用已知为通过扩增浓缩（无转录的SELEX）的配体的无转录系统进化的方法生产针对靶分子的核酸配体的方法。 无转录的SELEX方法通过将这些片段退火成互补模板，然后将片段连接在一起，将合成核酸片段的核酸配体组装起来。

公开(公告)号：US06194550B1

公开(公告)日：2001-02-27

申请号：US09197649

申请日：1998-11-23

申请人： Larry Gold ,  Craig Tuerk ,  David Pribnow ,  Jonathan Drew Smith

发明人： Larry Gold ,  Craig Tuerk ,  David Pribnow ,  Jonathan Drew Smith

IPC分类号： C12N1511

CPC分类号： C12N15/1041 ,  C12Q1/6806 ,  G01N33/68

摘要： A method for preparing polypeptide ligands of target molecules wherein candidate mixtures comprised of ribosome complexes or mRNA•polypeptide copolymers are partitioned relative to their affinity to the target and amplified to create a new candidate mixture enriched in ribosome complexes or mRNA•polypeptide copolymers with an affinity to the target.

摘要翻译： 制备靶分子的多肽配体的方法，其中由核糖体复合物或mRNA多肽共聚物组成的候选混合物相对于它们对靶的亲和力被分配，并被扩增，以产生富含核糖体复合物或具有亲和力的mRNA多肽共聚物的新候选混合物 到目标。

公开(公告)号：US5843701A

公开(公告)日：1998-12-01

申请号：US829461

申请日：1992-01-31

申请人： Larry Gold ,  Craig Tuerk ,  David Pribnow ,  Jonathan Drew Smith

发明人： Larry Gold ,  Craig Tuerk ,  David Pribnow ,  Jonathan Drew Smith

IPC分类号： C12N15/10 ,  C12Q1/68 ,  G01N33/68 ,  C12P21/02 ,  C12N15/00

CPC分类号： C12N15/1041 ,  G01N33/68 ,  C12Q1/6806

摘要： A method for preparing polypeptide ligands of target molecules wherein candidate mixtures comprised of ribosome complexes or mRNA.multidot.polypeptide copolymers are partitioned relative to their affinity to the target and amplified to create a new candidate mixture enriched in ribosome complexes or mRNA.multidot.polypeptide copolymers with an affinity to the target.

摘要翻译： 制备靶分子的多肽配体的方法，其中由核糖体复合物或mRNA多聚体共聚物组成的候选混合物相对于其对靶的亲和力被分配，并被扩增，以产生富含核糖体复合物或mRNAx多肽共聚物的新候选混合物，其与靶标具有亲和力。

公开(公告)号：US20100196877A1

公开(公告)日：2010-08-05

申请号：US12663686

申请日：2008-06-13

申请人： Jonathan Drew Smith ,  Jon C. Rees ,  Duane Bush ,  Breanna Leigh Dreiling ,  Maria Izzo ,  Breanna Christine Smith ,  Bernard Sportmann ,  Tiffany Steinmark ,  Richard Proctor

发明人： Jonathan Drew Smith ,  Jon C. Rees ,  Duane Bush ,  Breanna Leigh Dreiling ,  Maria Izzo ,  Breanna Christine Smith ,  Bernard Sportmann ,  Tiffany Steinmark ,  Richard Proctor

IPC分类号： C12Q1/70

CPC分类号： G01N33/56911

摘要： A method of determining the presence or absence of a target microorganism in a sample to be tested, the method comprising: combining with the sample an amount of bacteriophage capable of attaching to the target microorganism to create a bacteriophage exposed sample, and a substance which enhances bacteriophage amplification or sensitivity; providing conditions to the bacteriophage-exposed sample sufficient to allow the bacteriophage to infect the microorganism; and assaying the bacteriophage-exposed sample to detect the presence or absence of a bacteriophage marker to determine the presence or absence of the target microorganism.

摘要翻译： 一种确定待测试样品中目标微生物的存在或不存在的方法，所述方法包括：与样品结合能够附着于靶微生物以产生噬菌体暴露样品的噬菌体的量和增强的物质 噬菌体扩增或敏感性; 为足以允许噬菌体感染微生物的噬菌体暴露样品提供条件; 并测定噬菌体暴露的样品以检测噬菌体标志物的存在或不存在，以确定目标微生物的存在或不存在。

公开(公告)号：US20080160535A1

公开(公告)日：2008-07-03

申请号：US12030024

申请日：2008-02-12

申请人： Larry Gold ,  Jonathan Drew Smith ,  Dominic Zichi ,  Daniel J. Schneider ,  Chad Greef

发明人： Larry Gold ,  Jonathan Drew Smith ,  Dominic Zichi ,  Daniel J. Schneider ,  Chad Greef

IPC分类号： C12Q1/68 ,  C40B60/10 ,  C07H21/04

CPC分类号： C12N15/115 ,  G01N33/58

摘要： The present invention provides novel methods and reagents for detecting the binding of protein targets to nucleic acid ligands. Using Universal Protein Stains (UPS), proteins bound by nucleic acid ligands may be labeled with a detectable moiety. The methods and reagents are particularly useful for the detection of protein targets bound to multiplexed arrays of nucleic acid ligands. The present invention also provides novel methods for the multiplexed evaluation of photocrosslinking nucleic acid ligands. The methods allow one simultaneously to: (1) evaluate the performance (dynamic range) of a plurality of photocrosslinking nucleic acid ligands; and (2) assess the specificity of each photocrosslinking nucleic acid ligand for its cognate target protein. Photocrosslinking nucleic acid ligands with the most desirable properties can then be selected for use in diagnostic and prognostic medical assays. The present invention also provides a photocrosslinking nucleic acid ligand that binds specifically to HIV gp120MN.

摘要翻译： 本发明提供用于检测蛋白质靶标与核酸配体的结合的新型方法和试剂。 使用通用蛋白污渍（UPS），可以用可检测的部分标记由核酸配体结合的蛋白质。 所述方法和试剂对于检测与核酸配体复合阵列结合的蛋白质靶标特别有用。 本发明还提供了用于光交联核酸配体的多重评价的新方法。 该方法同时允许：（1）评估多个光交联核酸配体的性能（动态范围）; 和（2）评估每个光交联核酸配体对其同源靶蛋白的特异性。 然后可以选择具有最理想特性的光交联核酸配体用于诊断和预后医学测定。 本发明还提供了与HIV gp120MN特异性结合的光交联核酸配体。

公开(公告)号：US08216780B2

公开(公告)日：2012-07-10

申请号：US12476796

申请日：2009-06-02

申请人： Jonathan Drew Smith ,  Breanna Leigh Dreiling ,  Breanna Christine Smith ,  John H. Wheeler

发明人： Jonathan Drew Smith ,  Breanna Leigh Dreiling ,  Breanna Christine Smith ,  John H. Wheeler

IPC分类号： C12Q1/70 ,  C12Q1/02

CPC分类号： C12Q1/04 ,  G01N33/54326 ,  G01N33/56911

摘要： A method of determining the presence or absence of a target microorganism in a sample to be tested, the method comprising: (a) combining with the sample an amount of bacteriophage capable of attaching to the target microorganism to create a bacteriophage-exposed sample; (b) providing conditions to the bacteriophage-exposed sample sufficient to allow the bacteriophage to attach to the target microorganism while inhibiting phage replication in a potentially cross-reactive, non-target microorganism; and (c) assaying the bacteriophage-exposed sample to detect the presence or absence of a bacteriophage marker to determine the presence or absence of the target microorganism; wherein the amount of the bacteriophage is between 10% to 70% of the threshold number of bacteriophage that the assay can detect, or between 1×106 pfu/mL and 7×106 pfu/mL.

摘要翻译： 一种确定待测试样品中目标微生物的存在或不存在的方法，所述方法包括：（a）与样品结合能够附着于靶微生物以产生噬菌体暴露样品的噬菌体数量; （b）向噬菌体暴露的样品提供足以允许噬菌体附着于靶微生物同时抑制潜在交叉反应性非目标微生物中的噬菌体复制的条件; 和（c）测定噬菌体暴露的样品以检测噬菌体标志物的存在或不存在以确定靶微生物的存在或不存在; 其中噬菌体的量在测定可检测的噬菌体阈值的10％至70％之间，或1×10 6 pfu / mL至7×10 6 pfu / mL之间。