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61.发明授权
公开(公告)号：US5693463A
公开(公告)日：1997-12-02
申请号：US996783
申请日：1992-12-23
IPC分类号： C07K14/47 , C12N15/09 , C12N15/10 , C12N15/67 , C12Q1/68 , C12Q1/70 , C07H21/02 , C12N15/00 , G01N33/574
CPC分类号： C12N15/67 , C07K14/47 , C12N15/1048 , C12Q1/6811 , C12Q1/6883 , C12Q1/705
摘要： 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.
摘要翻译： 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。
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公开(公告)号：US5635602A
公开(公告)日：1997-06-03
申请号：US107186
申请日：1993-08-13
申请人： Charles R. Cantor , Roy S. Chuck , Doris B. Tse
发明人： Charles R. Cantor , Roy S. Chuck , Doris B. Tse
CPC分类号： C07K16/2812 , C07K16/2809 , C07K16/468
摘要： The invention relates to bis-protein-DNA conjugates. A protein having an antigen specific binding activity is covalently linked to each end of a derivatized DNA molecule. The bis-protein-DNA conjugates can be used for immunoassays and measuring distances between proteins at up to 3.4 .ANG. resolution. The invention also relates to methods of synthesizing these bis-protein-DNA conjugates. Synthesis of the conjugates entails derivatizing the 5' or 3' end of a DNA oligonucleotide and covalently linking that DNA to a protein. The DNA can be indirectly conjugated to an antibody or Fab' fragment, using a avidin/streptavidin-biotin linkage. The conjugates of the invention can be used in immunoassays and PCR assays.
摘要翻译： 本发明涉及双蛋白-DNA缀合物。 具有抗原特异性结合活性的蛋白质与衍生的DNA分子的每个末端共价连接。 双蛋白-DNA缀合物可用于免疫测定，并以高达3.4 ANGSTROM分辨率测量蛋白质之间的距离。 本发明还涉及合成这些双蛋白-DNA缀合物的方法。 共轭物的合成需要衍生DNA寡核苷酸的5'或3'末端并共价连接该DNA与蛋白质。 可以使用抗生物素蛋白/链霉抗生物素蛋白 - 生物素连接，将DNA间接缀合至抗体或Fab'片段。 本发明的缀合物可用于免疫测定和PCR测定。
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公开(公告)号：US5503980A
公开(公告)日：1996-04-02
申请号：US322526
申请日：1994-10-17
申请人： Charles R. Cantor
发明人： Charles R. Cantor
CPC分类号： B01J19/0046 , C12Q1/6837 , C40B80/00 , B01J2219/00527 , B01J2219/00529 , B01J2219/0059 , B01J2219/00605 , B01J2219/0061 , B01J2219/00612 , B01J2219/00626 , B01J2219/00637 , B01J2219/00648 , B01J2219/00659 , B01J2219/00722 , C40B40/06
摘要： This invention is directed to methods for determining a nucleotide sequence of a nucleic acid using positional sequencing by hybridization, and to the creation of nucleic acids probes which may be used with these methods. This invention is also directed to diagnostic aids for analyzing the nucleic acid composition and content of biological samples, including samples derived from medical and agricultural sources.
摘要翻译： 本发明涉及使用通过杂交的位置测序确定核酸的核苷酸序列的方法，以及可以与这些方法一起使用的核酸探针的产生。 本发明还涉及用于分析生物样品的核酸组成和含量的诊断助剂，包括衍生自医学和农业来源的样品。
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公开(公告)号：US5306619A
公开(公告)日：1994-04-26
申请号：US81070
申请日：1993-06-22
IPC分类号： C07K14/47 , C12N15/09 , C12N15/10 , C12N15/67 , C12Q1/68 , C12Q1/70 , C07H17/00 , C12Q1/00 , G01N33/566
CPC分类号： C12N15/67 , C07K14/47 , C12N15/1048 , C12Q1/6811 , C12Q1/6883 , C12Q1/705
摘要： 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. Also described herein is a method to capture DNA that has been released from the DNA:protein complex.
摘要翻译： 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。 本文还描述了捕获已经从DNA：蛋白质复合物释放的DNA的方法。
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公开(公告)号：US09534224B2
公开(公告)日：2017-01-03
申请号：US10535128
申请日：2003-11-14
CPC分类号： C12N15/67 , C12N15/11 , C12N2310/53 , C12Q1/6897
摘要： The present invention provides nucleic acid molecules, DNA constructs, plasmids, and methods for post-transcriptional regulation of gene expression using RNA molecules to both repress and activate translation of an open reading frame. Repression of gene expression is achieved through the presence of a regulatory nucleic acid element (the cis-repressive RNA or crRNA) within the 5′ untranslated region (5′ UTR) of an mRNA molecule. The nucleic acid element forms a hairpin (stem/loop) structure through complementary base pairing. The hairpin blocks access to the mRNA transcript by the ribosome, thereby preventing translation. In particular, in embodiments of the invention designed to operate in prokaryotic cells, the stem of the hairpin secondary structure sequesters the ribosome binding site (RBS). In embodiments of the invention designed to operate in eukaryotic cells, the stem of the hairpin is positioned upstream of the start codon, anywhere within the 5′ UTR of an mRNA. A small RNA (trans-activating RNA, or taRNA), expressed in trans, interacts with the crRNA and alters the hairpin structure. This alteration allows the ribosome to gain access to the region of the transcript upstream of the start codon, thereby activating transcription from its previously repressed state.
摘要翻译： 本发明提供核酸分子，DNA构建体，质粒和用于转录后调节基因表达的方法，其使用RNA分子抑制和激活开放阅读框的翻译。 通过在mRNA分子的5'非翻译区（5'UTR）内存在调节性核酸元件（顺式抑制性RNA或crRNA）来实现基因表达的抑制。 核酸元件通过互补碱基配对形成发夹（茎/环）结构。 发夹阻止核糖体进入mRNA转录物，从而阻止翻译。 特别地，在设计用于在原核细胞中操作的本发明的实施方案中，发夹二级结构的茎螯合核糖体结合位点（RBS）。 在设计用于在真核细胞中操作的本发明的实施方案中，发夹的茎位于起始密码子的上游，位于mRNA的5'UTR内的任何位置。 以反式表达的小RNA（反式激活RNA或taRNA）与crRNA相互作用并改变发夹结构。 这种改变允许核糖体进入起始密码子上游的转录物区域，从而从其先前的抑制状态激活转录。
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66.发明授权公开(公告)号：US09034580B2
公开(公告)日：2015-05-19
申请号：US12354749
申请日：2009-01-15
申请人： Charles R. Cantor
发明人： Charles R. Cantor
CPC分类号： C12Q1/6876 , C12Q1/6806 , C12Q1/6837 , C12Q1/6844 , C12Q2565/537 , C12Q2565/519 , C12Q2565/501 , C12Q2531/101 , C12Q2525/161 , C12Q2525/155
摘要： Improved solid supports and methods for analyzing target nucleotide sequences are provided herein. Certain improvements are directed to efficiently preparing nucleic acids that comprise nucleotide sequences identical to or substantially identical to one or more target nucleotide sequences, or complement thereof. The prepared nucleic acids include a reference sequence that facilitates sequence analysis. The solid supports and methods provided herein minimize the number of steps required by published sequence analysis methodologies, and thereby offer improved sequence analysis efficiency.
摘要翻译： 本文提供了改进的固体支持物和分析靶核苷酸序列的方法。 某些改进旨在有效地制备包含与一个或多个靶核苷酸序列或其互补序列相同或基本相同的核苷酸序列的核酸。 所制备的核酸包括促进序列分析的参考序列。 本文提供的固体支持物和方法使发布的序列分析方法所需的步骤数量最小化，从而提供改进的序列分析效率。
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公开(公告)号：US20110263453A1
公开(公告)日：2011-10-27
申请号：US13129797
申请日：2009-11-20
申请人： Charles R. Cantor
发明人： Charles R. Cantor
摘要： Described herein are products and processes for nucleic acid quantification, which are in part useful for detecting and determining the nucleotide sequence of rare nucleic acids (i.e., low copy number nucleic acids) in a sample. Such products and processes are useful for reducing the dynamic range among different nucleic acid species.
摘要翻译： 本文描述的是用于核酸定量的产物和方法，其部分可用于检测和测定样品中稀有核酸（即低拷贝数核酸）的核苷酸序列。 这样的产物和方法可用于减少不同核酸物种之间的动态范围。
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公开(公告)号：US08034567B2
公开(公告)日：2011-10-11
申请号：US10655762
申请日：2003-09-05
申请人： Charles R. Cantor , Chunming Ding
发明人： Charles R. Cantor , Chunming Ding
CPC分类号： C12Q1/6851 , C12Q2545/107 , C12Q2535/125 , C12Q2525/186
摘要： The present invention relates to a method for measuring the amount of a target nucleic acid in a sample using a standard which is designed to have one base difference compared with the gene of interest or a “target nucleic acid sequence.” Use of such standard in combination with a method of “enhancing” the difference in the standard and the test nucleic acid sample using, for example, a base extension reaction carried right at the mutation site allowing amplification of the standard and target nucleic acids with the same efficiency and facilitating quantification of the target nucleic acid. Thereafter a means of quantifying the “enhanced” standard and target nucleic acid samples is used to determine the amount of the target nucleic acid. In the preferred embodiment, the quantification means is Mass Spectrometry.
摘要翻译： 本发明涉及使用与目的基因相比具有一个碱基差异的标准或“靶核酸序列”来测量样品中靶核酸量的方法。使用这种标准物 结合使用例如在突变位点上携带的碱基延伸反应来“提高”标准差和测试核酸样品的方法，允许以相同的效率扩增标准品和靶核酸并促进定量 的靶核酸。 此后，使用定量“增强”标准和靶核酸样品的手段来确定靶核酸的量。 在优选实施方案中，定量方法是质谱法。
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公开(公告)号：US20100184075A1
公开(公告)日：2010-07-22
申请号：US12704043
申请日：2010-02-11
申请人： Charles R. Cantor , Chunming Ding
发明人： Charles R. Cantor , Chunming Ding
IPC分类号： C12Q1/68
CPC分类号： C12Q1/6827 , C12Q1/6858 , C12Q2600/156 , C12Q2527/137 , C12Q2537/143 , C12Q2565/627
摘要： The present invention provides an efficient way for high throughput haplotype analysis. Several polymorphic nucleic acid markers, such as SNPs, can be simultaneously and reliably determined through multiplex PCR of single nucleic acid molecules in several parallel single molecule dilutions and the consequent statistical analysis of the results from these parallel single molecule multiplex PCR reactions results in reliable determination of haplotypes present in the subject. The nucleic acid markers can be of any distance to each other on the chromosome. In addition, an approach wherein overlapping DNA markers are analyzed can be used to link smaller haplotypes into larger haplotypes. Consequently, the invention provides a powerful new tool for diagnostic haplotyping and identifying novel haplotypes.
摘要翻译： 本发明提供了高通量单倍型分析的有效方法。 可以通过多个平行的单分子稀释物中的单个核酸分子的多重PCR来同时并可靠地测定几种多态性核酸标记，例如SNP，并且随后对来自这些平行的单分子多重PCR反应的结果的统计分析导致可靠的测定 的单倍体存在于受试者。 核酸标记在染色体上可以彼此有任何距离。 此外，分析重叠的DNA标记物的方法可用于将较小的单倍型连接到较大的单元型中。 因此，本发明为诊断单倍型和鉴定新型单体型提供了强大的新工具。
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70.发明申请公开(公告)号：US20090220942A1
公开(公告)日：2009-09-03
申请号：US12091709
申请日：2006-10-27
CPC分类号： C12Q1/6883
摘要： The present invention relates to a method to produce activated split-polypeptide fragments that on reconstitution immediately forms an active protein. The method relate to real-time protein complementation. Also encompassed in the invention is a method to split and produce split-fluorescent proteins in an active state which produce a fluorescent signal immediately on reconstitution. The present application also provides methods to detect nucleic acids; non-nucleic acid analytes and nucleic acid hybridization in real-time using the novel activated split-polypeptide fragments of the invention.
摘要翻译： 本发明涉及一种产生活化的裂多肽片段的方法，其在重构时立即形成活性蛋白质。 该方法涉及实时蛋白质互补。 本发明还包括分裂和产生活性状态的分裂荧光蛋白的方法，其在重建时立即产生荧光信号。 本申请还提供了检测核酸的方法; 非核酸分析物和核酸杂交，使用本发明的新型活化的裂解多肽片段。
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