公开(公告)号：US20090305237A1

公开(公告)日：2009-12-10

申请号：US11914970

申请日：2006-05-26

Applicant: Charles R. Cantor ,  Lingang Zhang ,  Simon Kasif

Inventor： Charles R. Cantor ,  Lingang Zhang ,  Simon Kasif

IPC: C12Q1/68

CPC classification number: C12Q1/6816 ,  C12Q1/6809 ,  C12Q2565/627 ,  C12Q2563/167 ,  C12Q2545/114

Abstract: The invention provides a method for detecting and quantifying the amount of target molecules, such as nucleic acids or proteins in a sample. The target molecules are first recognized and bounded by target-specific probes, generally nucleic acids or proteins that bind specifically to the targets, each of which is labeled with a short single-stranded nucleic acid probe, either DNA or RNA, with distinct molecular weight. This label is called an oligonucleotide mass tag. One or several standard oligonucleotide sequences can be designed with similar sequence but distinct molecular weight to those oligonucleotide mass tags. Then the oligonucleotide mass tags associated with bounded probes and the standard sequences are co-amplified using a pair of common primers. The presence and/or amount of each oligonucleotide mass tag, which corresponds to the amount of corresponding target molecule, is determined by a primer extension reaction and quantification of the primer extension product.

Abstract translation: 本发明提供了用于检测和定量样品中靶分子如核酸或蛋白质的量的方法。 目标分子首先被目标特异性探针识别并限制，通常是与靶标特异性结合的核酸或蛋白质，其中每个标记有短单链核酸探针，DNA或RNA，具有不同的分子量 。 该标签称为寡核苷酸质量标签。 可以设计一个或几个标准寡核苷酸序列，其具有与那些寡核苷酸质量标签相似的序列但分子量不同。 然后使用一对普通引物共同扩增与有界探针和标准序列相关的寡核苷酸质粒标签。 通过引物延伸反应和引物延伸产物的定量来确定对应于相应靶分子量的每个寡核苷酸质粒标签的存在和/或量。

公开(公告)号：US07569341B2

公开(公告)日：2009-08-04

申请号：US08967269

申请日：1997-11-07

Applicant: Christof M. Niemeyer ,  Charles R. Cantor ,  Takeshi Sano ,  Cassandra L. Smith

Inventor： Christof M. Niemeyer ,  Charles R. Cantor ,  Takeshi Sano ,  Cassandra L. Smith

IPC: C12Q1/68

CPC classification number: B82Y5/00 ,  A61K47/54 ,  A61K47/55 ,  A61K47/557 ,  A61K47/6949 ,  A61K51/1268 ,  C03C17/30 ,  C03C17/3405 ,  C12Q1/6804 ,  C12Q1/682

Abstract: The invention relates to supramolecular bioconjugates and to methods for assembling and utilizing supramolecular bioconjugates. Supramolecular bioconjugates comprise a plurality of first nucleic acids and a plurality of mediators wherein each mediator comprises a second nucleic acid complementary to a sequence within said plurality of first nucleic acids. To assemble a supramolecular bioconjugate, one or more sets of bioreactive agents are coupled to the plurality of mediators, forming a plurality of bioreactive complexes The plurality of bioreactive complexes are hybridized to the plurality of first nucleic acids to form the supramolecular bioconjugate. Bioconjugates can be used to detect and isolate targets, to screen samples for targets such as antigens, to treat patients with multiple agents or to diagnose disorders in the form of a kit.

Abstract translation: 本发明涉及超分子生物缀合物和组分和利用超分子生物缀合物的方法。 超分子生物缀合物包含多个第一核酸和多个介体，其中每个介体包含与所述多个第一核酸内的序列互补的第二核酸。 为了组装超分子生物缀合物，将一组或多组生物反应剂偶联到多个介体中，形成多个生物反应性复合物。多个生物反应性复合物与多个第一核酸杂交以形成超分子生物缀合物。 生物共轭物可用于检测和分离靶标，筛选靶标如抗原的样品，以治疗患有多种药物的患者或以试剂盒的形式诊断疾病。

公开(公告)号：US07470517B2

公开(公告)日：2008-12-30

申请号：US11547765

申请日：2005-04-08

Applicant: Charles R. Cantor ,  Fouad A. Siddiqi

Inventor： Charles R. Cantor ,  Fouad A. Siddiqi

IPC: C12Q1/68

CPC classification number: C12Q1/6872 ,  C12Q2525/101 ,  C12Q2523/107

Abstract: The present invention provides a method for determining nucleic acid sequences of a template nucleic acid that requires no prior knowledge of the nucleic acid sequence present in the template nucleic acid. The method is based on combining information about the mass of a fragment, the mass of any one nucleotide and the combinations thereof, and the sequence specificity of a nucleotide cutter, either enzymatic or chemical cutter, to determine a sequence of a nucleic acid fragment. This method allows for de novo detection of sequences in a target nucleic acid without requiring any prior sequence information. This method is called Partial Sequencing by Fragmentation (PSBF) and it works by fragmenting a target into oligo- or polynucleotides whose masses or lengths are uniquely associated with known sequences. The identities of these sequences are determined solely by the specific fragmentation method used, and are always independent of the target. PSBF can be implemented using electrophoresis, mass spectrometry or any other method that can be used to distinguish the size of the cut nucleic acid sequence fragments.

Abstract translation: 本发明提供了一种确定模板核酸的核酸序列的方法，其不需要模板核酸中存在的核酸序列的先验知识。 该方法基于组合关于片段的质量，任何一个核苷酸的质量及其组合的信息以及核苷酸切割剂（酶或化学切割机）的序列特异性，以确定核酸片段的序列。 该方法允许从头检测靶核酸中的序列，而不需要任何先前的序列信息。 这种方法被称为通过片段化分段测序（PSBF），它的作用是通过将目标片段分成其质量或长度与已知序列唯一相关的寡核苷酸或多核苷酸。 这些序列的身份完全由所使用的具体碎片方法确定，并且始终与目标无关。 PSBF可以使用电泳，质谱法或可用于区分切割的核酸序列片段的大小的任何其它方法来实现。

公开(公告)号：US06869765B2

公开(公告)日：2005-03-22

申请号：US09993346

申请日：2001-11-13

Applicant: Cynthia A. Edwards ,  Charles R. Cantor ,  Beth M. Andrews ,  Lisa M. Turin ,  Kirk E. Fry

Inventor： Cynthia A. Edwards ,  Charles R. Cantor ,  Beth M. Andrews ,  Lisa M. Turin ,  Kirk E. Fry

IPC: C07K14/47 ,  C12N15/10 ,  C12N15/67 ,  C12Q1/68 ,  C12Q1/70

CPC classification number: C12Q1/701 ,  C07K14/47 ,  C12N15/1048 ,  C12N15/67 ,  C12Q1/6811 ,  C12Q1/6813 ,  C12Q1/6876 ,  C12Q1/6883 ,  C12Q1/705 ,  H01L2924/14 ,  C12Q2525/161 ,  C12Q2525/131 ,  C12Q2537/161 ,  C12Q2522/101 ,  C12Q2521/301

Abstract: The present invention defines a DNA: protein-binding assay useful for screening libraries of synthetic or biological compounds for their ability to bind DNA test sequences. The assay is versatile in that any number of test sequences can be tested by placing the test sequence adjacent to a defined protein binding screening sequence. Binding of molecules to these test sequence changes the binding characteristics of the protein molecule to its cognate binding sequence. When such a molecule binds the test sequence the equilibrium of the DNA:protein complexes is disturbed, generating changes in the concentration of free DNA probe. Numerous exemplary target test sequences (SEQ ID NO:1 to SEQ ID NO:600) are set forth. The assay of the present invention is also useful to characterize the preferred binding sequences of any selected DNA-binding molecule.

Abstract translation: 本发明定义了一种DNA：蛋白结合测定法，用于筛选合成或生物化合物文库结合DNA测试序列的能力。 该测定法是通用的，因为可以通过将测试序列置于与定义的蛋白质结合筛选序列相邻的位置来测试任何数量的测试序列。 分子与这些测试序列的结合改变了蛋白质分子与其同源结合序列的结合特征。 当这样的分子结合测试序列时，DNA：蛋白复合物的平衡受到干扰，产生游离DNA探针浓度的变化。 阐述了许多示例性目标测试序列（SEQ ID NO：1至SEQ ID NO：600）。 本发明的测定也可用于表征任何所选DNA结合分子的优选结合序列。

公开(公告)号：US06207390B1

公开(公告)日：2001-03-27

申请号：US08941100

申请日：1997-10-03

Applicant: Charles R. Cantor ,  Takeshi Sano

Inventor： Charles R. Cantor ,  Takeshi Sano

IPC: G01N3353

CPC classification number: G01N33/538 ,  A61K38/00 ,  C07K14/36 ,  G01N2333/465 ,  Y10S530/808 ,  Y10S530/81

Abstract: The present invention relates to methods for contacting biological targets using a mutated streptavidin protein having a reduced affinity for biotin.

Abstract translation: 本发明涉及使用对生物素具有降低的亲和力的突变链霉抗生物素蛋白接触生物靶标的方法。

公开(公告)号：US5965133A

公开(公告)日：1999-10-12

申请号：US967297

申请日：1997-11-07

Applicant: Charles R. Cantor ,  Christof M. Niemeyer ,  Cassandra L. Smith ,  Takeshi Sano ,  Donald J. Hnatowich ,  Mary Rusckowski

Inventor： Charles R. Cantor ,  Christof M. Niemeyer ,  Cassandra L. Smith ,  Takeshi Sano ,  Donald J. Hnatowich ,  Mary Rusckowski

IPC: G01N33/566 ,  A61K38/00 ,  A61K38/16 ,  A61K38/21 ,  A61K38/22 ,  A61K38/27 ,  A61K38/43 ,  A61K39/00 ,  A61K39/395 ,  A61K45/00 ,  A61K47/48 ,  A61K49/00 ,  A61K51/00 ,  A61K51/12 ,  A61P31/04 ,  A61P31/12 ,  A61P35/00 ,  A61P35/02 ,  C03C17/30 ,  C03C17/34 ,  C07H21/04 ,  C12N15/09 ,  C12Q1/68 ,  A61K31/70

CPC classification number: B82Y5/00 ,  A61K47/481 ,  A61K47/48146 ,  A61K47/48961 ,  A61K51/1268 ,  C03C17/30 ,  C03C17/3405 ,  C12Q1/6804 ,  C12Q1/682 ,  Y10S977/80 ,  Y10S977/808 ,  Y10S977/898 ,  Y10S977/906 ,  Y10S977/92

Abstract: The invention is directed to constructs and compositions containing multimeric forms of nucleic acid. Multimeric nucleic acids comprise single-stranded nucleic acids attached via biotin to streptavidin and bound with a functional group. These constructs can be utilized in vivo to treat or identify diseased tissue or cells. Repeated administrations of multimeric nucleic acid compositions produce a rapid and specific amplification of nucleic acid constructs and their attached functional groups. For treatment purposes, functional groups may be toxins, radioisotopes, genes or enzymes. Diagnostically, labeled multimeric constructs may be used to identify specific targets in vivo or in vitro. Multimeric nucleic acids may also be used in nanotechnology and to create self-assembling polymeric aggregates such as membranes of defined porosity, microcircuits and many other products.

Abstract translation: 本发明涉及包含核酸的多聚体形式的构建体和组合物。 多聚核酸包含通过生物素与链霉亲和素连接并与官能团结合的单链核酸。 这些构建体可以在体内用于治疗或鉴定患病组织或细胞。 多重核酸组合物的重复施用产生核酸构建体及其连接的官能团的快速和特异性扩增。 为了治疗目的，官能团可以是毒素，放射性同位素，基因或酶。 在诊断上，标记的多聚体构建体可用于在体内或体外鉴定特异性靶标。 多聚核酸也可用于纳米技术，并且可以产生自组装聚合物聚集体，例如确定的孔隙率的膜，微电路和许多其他产物。

公开(公告)号：US5869241A

公开(公告)日：1999-02-09

申请号：US475228

申请日：1995-06-07

Applicant: Cynthia A. Edwards ,  Charles R. Cantor ,  Beth M. Andrews ,  Lisa M. Turin ,  Kirk E. Fry

Inventor： Cynthia A. Edwards ,  Charles R. Cantor ,  Beth M. Andrews ,  Lisa M. Turin ,  Kirk E. Fry

IPC: C07K14/47 ,  C12N15/10 ,  C12N15/67 ,  C12Q1/68 ,  C12Q1/70 ,  C12P19/34

CPC classification number: C12Q1/701 ,  C07K14/47 ,  C12N15/1048 ,  C12N15/67 ,  C12Q1/6811 ,  C12Q1/6813 ,  C12Q1/6876 ,  C12Q1/6883 ,  C12Q1/705 ,  H01L2924/14

Abstract: The present invention defines a DNA:protein-binding assay useful for screening libraries of synthetic or biological compounds for their ability to bind DNA test sequences. The assay is versatile in that any number of test sequences can be tested by placing the test sequence adjacent to a defined protein binding screening sequence. Binding of molecules to these test sequence changes the binding characteristics of the protein molecule to its cognate binding sequence. When such a molecule binds the test sequence the equilibrium of the DNA:protein complexes is disturbed, generating changes in the concentration of free DNA probe. Numerous exemplary target test sequences (SEQ ID NO:1 to SEQ ID NO:600) are set forth. The assay of the present invention is also useful to characterize the preferred binding sequences of any selected DNA-binding molecule.

Abstract translation: 本发明定义了一种DNA：蛋白结合测定法，用于筛选合成或生物化合物文库结合DNA测试序列的能力。 该测定法是通用的，因为可以通过将测试序列置于与定义的蛋白质结合筛选序列相邻的位置来测试任何数量的测试序列。 分子与这些测试序列的结合改变了蛋白质分子与其同源结合序列的结合特征。 当这样的分子结合测试序列时，DNA：蛋白复合物的平衡受到干扰，产生游离DNA探针浓度的变化。 阐述了许多示例性目标测试序列（SEQ ID NO：1至SEQ ID NO：600）。 本发明的测定也可用于表征任何所选DNA结合分子的优选结合序列。

公开(公告)号：US5753439A

公开(公告)日：1998-05-19

申请号：US446102

申请日：1995-05-19

Applicant: Cassandra L. Smith ,  Ron Yaar ,  Przemyslaw Szafranski ,  Charles R. Cantor

Inventor： Cassandra L. Smith ,  Ron Yaar ,  Przemyslaw Szafranski ,  Charles R. Cantor

IPC: C12Q1/68 ,  C07H21/04 ,  C12P19/34 ,  C12Q1/70

CPC classification number: C12Q1/6827 ,  C12Q1/6823

Abstract: The invention relates to methods for rapidly determining the sequence and/or length a target sequence. The target sequence may be a series of known or unknown repeat sequences which are hybridized to an array of probes. The hybridized array is digested with a single-strand nuclease and free 3'-hydroxyl groups extended with a nucleic acid polymerase. Nuclease cleaved heteroduplexes can be easily distinguish from nuclease uncleaved heteroduplexes by differential labeling. Probes and target can be differentially labeled with detectable labels. Matched target can be detected by cleaving resulting loops from the hybridized target and creating free 3-hydroxyl groups. These groups are recognized and extended by polymerases added into the reaction system which also adds or releases one label into solution. Analysis of the resulting products using either solid phase or solution. These methods can be used to detect characteristic nucleic acid sequences, to determine target sequence and to screen for genetic defects and disorders. Assays can be conducted on solid surfaces allowing for multiple reactions to be conducted in parallel and, if desired, automated.

Abstract translation: 本发明涉及用于快速确定靶序列的序列和/或长度的方法。 靶序列可以是与探针阵列杂交的一系列已知或未知的重复序列。 杂交阵列用单链核酸酶消化，游离的3'-羟基用核酸聚合酶延伸。 核酸酶切割的异源双链体可以通过差异标记容易地与核酸酶未切割的异源双链体区分开。 探针和靶可以用可检测的标记差异标记。 可以通过从杂交靶标切割得到的环并产生游离的3-羟基来检测匹配的靶。 这些基团被加入到反应体系中的聚合酶识别和扩增，该反应体系也将一个标记物添加或释放到溶液中。 使用固相或溶液分析所得产物。 这些方法可用于检测特征性核酸序列，确定靶序列并筛选遗传缺陷和病症。 测定可以在固体表面进行，允许并行进行多个反应，如果需要，可以自动进行。

公开(公告)号：US5716780A

公开(公告)日：1998-02-10

申请号：US484499

申请日：1995-06-07

Applicant: Cynthia A. Edwards ,  Kirk E. Fry ,  Charles R. Cantor ,  Beth M. Andrews

Inventor： Cynthia A. Edwards ,  Kirk E. Fry ,  Charles R. Cantor ,  Beth M. Andrews

IPC: C07K14/47 ,  C12N15/09 ,  C12N15/10 ,  C12N15/67 ,  C12Q1/68 ,  C12Q1/70 ,  G01N33/566

CPC classification number: C12N15/67 ,  C07K14/47 ,  C12N15/1048 ,  C12Q1/6811 ,  C12Q1/6883 ,  C12Q1/705

Abstract: The present invention defines an assay useful for screening libraries of synthetic or biological compounds for their ability to bind specific DNA test sequences. The assay is also useful for determining the sequence specificity and relative DNA-binding affinity of DNA-binding molecules for any particular DNA sequence. Also described herein are potential applications of the assay, including: 1) the detection of lead compounds or new drugs via the mass screening of libraries of synthetic or biological compounds (i.e., fermentation broths); 2) the design of sequence-specific DNA-binding drugs comprised of homo- or hetero-meric subunits of molecules for which the sequence specificity was determined using the assay; and 3) the use of molecules for which sequence specificity was determined using the assay as covalently attached moieties to aid in the binding of nucleic acid or other macromolecular polymers to nucleic acid sequences.

Abstract translation: 本发明定义了一种用于筛选合成或生物化合物文库以测定其结合特异性DNA测试序列的能力的测定法。 该测定还可用于确定DNA结合分子对于任何特定DNA序列的序列特异性和相对DNA结合亲和力。 本文还描述了测定的潜在应用，包括：1）通过大量筛选合成或生物化合物（即发酵液）文库来检测铅化合物或新药物; 2）由使用该测定法确定序列特异性的分子的同源或异源亚基组成的序列特异性DNA结合药物的设计; 和3）使用通过测定作为共价连接的部分确定序列特异性的分子，以有助于核酸或其它大分子聚合物与核酸序列的结合。

公开(公告)号：US5681745A

公开(公告)日：1997-10-28

申请号：US432017

申请日：1995-05-01

Applicant: Przemyslaw Szafranski ,  Charlene M. Mello ,  Takeshi Sano ,  Kenneth A. Marx ,  Charles R. Cantor ,  David L. Kaplan ,  Cassandra L. Smith

Inventor： Przemyslaw Szafranski ,  Charlene M. Mello ,  Takeshi Sano ,  Kenneth A. Marx ,  Charles R. Cantor ,  David L. Kaplan ,  Cassandra L. Smith

IPC: C07K14/36 ,  C07K14/465 ,  C12N1/21 ,  C12N15/12 ,  C12N15/70 ,  C12N5/10 ,  C12N1/13

CPC classification number: C12N15/70 ,  C07K14/36 ,  C07K14/465

Abstract: The present invention relates to genetic containment systems which express a biotin-binding component that can be used for selectively destroying recombinant cells such as genetically engineered microorganisms. These systems may comprise a streptavidin or an avidin gene whose expression is controlled by a regulatable promoter. The regulatory agent such as a transcriptional effector is expressed from another gene which may also be expressed and its expression controlled by the containment system. Expression of the agent can be designed to respond to physiological changes in the environment. The invention also relates to containment systems and methods for the selective detection or tracking of recombinant cells and to eukaryotic and prokaryotic cells which contain these genetic containment systems.

Abstract translation: 本发明涉及表达可用于选择性破坏重组细胞如遗传工程微生物的生物素结合成分的遗传容纳系统。 这些系统可以包含链霉亲和素或抗生物素蛋白基因，其表达受可调节启动子控制。 诸如转录效应子的调节剂由另外可能被表达的基因表达，其表达由遏制系统控制。 试剂的表达可以设计成响应环境中的生理变化。 本发明还涉及用于选择性检测或跟踪重组细胞和含有这些遗传包涵体系的真核和原核细胞的遏制系统和方法。