公开(公告)号：US5503980A

公开(公告)日：1996-04-02

申请号：US322526

申请日：1994-10-17

Applicant: Charles R. Cantor

Inventor： Charles R. Cantor

IPC: B01J19/00 ,  C12Q1/68 ,  C40B40/06 ,  C07H21/04 ,  C12P19/34

CPC classification number: 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

Abstract: 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.

Abstract translation: 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。

公开(公告)号：US5482836A

公开(公告)日：1996-01-09

申请号：US4552

申请日：1993-01-14

Applicant: Charles R. Cantor ,  Takashi Ito ,  Cassandra L. Smith

Inventor： Charles R. Cantor ,  Takashi Ito ,  Cassandra L. Smith

IPC: C12N15/10 ,  C12Q1/68 ,  C07H17/00 ,  C12N15/00 ,  C12P19/34

CPC classification number: C12Q1/6839 ,  C12N15/1003 ,  C12N15/101 ,  C12Q1/6806

Abstract: The invention provides a method for purifying or isolating double stranded DNA intact using triple helix formation. The method includes the steps of complexing an oligonucleotide and double stranded DNA to generate a triple helix and immobilization of the triple helix on a solid phase by means of a molecular recognition system such as avidin/biotin. The purified DNA is then recovered intact by treating the solid phase with a reagent that breaks the bonds between the oligonucleotide and the intact double stranded DNA while not affecting the Watson-Crick base pairs of the double helix. The present invention also provides a method for purifying or isolating double stranded DNA intact by complexing the double stranded DNA with a specific binding partner and recovering the complex during electrophoresis by immobilizing it on a solid phase trap imbedded in an electrophoretic gel.

Abstract translation: 本发明提供了使用三螺旋形成来纯化或分离完整的双链DNA的方法。 该方法包括以下步骤：使寡核苷酸和双链DNA复合以产生三螺旋，并通过分子识别系统如抗生物素蛋白/生物素将固定三固定在固相上。 然后通过用破坏寡核苷酸和完整双链DNA之间的键的试剂处理固相，同时不影响双螺旋的Watson-Crick碱基对，完整地回收纯化的DNA。 本发明还提供了通过使双链DNA与特异性结合配偶体络合来纯化或分离双链DNA的方法，并通过将其固定在嵌入电泳凝胶中的固相捕集器上，在电泳过程中回收该配合物。

公开(公告)号：US5306619A

公开(公告)日：1994-04-26

申请号：US81070

申请日：1993-06-22

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

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

IPC: C07K14/47 ,  C12N15/09 ,  C12N15/10 ,  C12N15/67 ,  C12Q1/68 ,  C12Q1/70 ,  C07H17/00 ,  C12Q1/00 ,  G01N33/566

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

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. Also described herein is a method to capture DNA that has been released from the DNA:protein complex.

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。 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。

公开(公告)号：US09534224B2

公开(公告)日：2017-01-03

申请号：US10535128

申请日：2003-11-14

Applicant: James J. Collins ,  Farren J. Isaacs ,  Charles R. Cantor ,  Daniel J. Dwyer

Inventor： James J. Collins ,  Farren J. Isaacs ,  Charles R. Cantor ,  Daniel J. Dwyer

IPC: C12N15/67 ,  C12N15/11 ,  C12Q1/68

CPC classification number: C12N15/67 ,  C12N15/11 ,  C12N2310/53 ,  C12Q1/6897

Abstract: 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.

Abstract translation: 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。

公开(公告)号：US09034580B2

公开(公告)日：2015-05-19

申请号：US12354749

申请日：2009-01-15

Applicant: Charles R. Cantor

Inventor： Charles R. Cantor

IPC: C12Q1/68 ,  C12P19/34

CPC classification number: C12Q1/6876 ,  C12Q1/6806 ,  C12Q1/6837 ,  C12Q1/6844 ,  C12Q2565/537 ,  C12Q2565/519 ,  C12Q2565/501 ,  C12Q2531/101 ,  C12Q2525/161 ,  C12Q2525/155

Abstract: 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.

Abstract translation: 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。

公开(公告)号：US20120156685A1

公开(公告)日：2012-06-21

申请号：US13412984

申请日：2012-03-06

Applicant: Charles R Cantor ,  Chunming Ding

Inventor： Charles R Cantor ,  Chunming Ding

IPC: G01N27/62

CPC classification number: C12Q1/6827 ,  C12Q2600/156 ,  C12Q2525/186 ,  C12Q2535/125 ,  C12Q2565/627 ,  C12Q2545/101

Abstract: The present invention is directed to a method for detecting and quantifying rare mutations in a nucleic acid sample. The nucleic acid molecules under investigation can be either DNA or RNA. The rare mutation can be any type of functional or non-functional nucleic acid change or mutation, such as deletion, insertion, translocation, inversion, one or more base substitution or polymorphism. Therefore, the methods of the present invention are useful in detection of rare mutations in, for example, diagnostic, prognostic and follow-up applications, when the targets are rare known nucleic acid variants mixed in with the wildtype or the more common nucleic acid variant(s).

Abstract translation: 本发明涉及一种用于检测和定量核酸样品中罕见突变的方法。 正在研究的核酸分子可以是DNA或RNA。 罕见突变可以是任何类型的功能或非功能性核酸变化或突变，例如缺失，插入，易位，反转，一个或多个碱基取代或多态性。 因此，当目标是罕见的已知的与野生型或更常见的核酸变体混合的核酸变体时，本发明的方法可用于检测例如诊断，预后和随访应用中的罕见突变 （s）。

公开(公告)号：US20110263453A1

公开(公告)日：2011-10-27

申请号：US13129797

申请日：2009-11-20

Applicant: Charles R. Cantor

Inventor： Charles R. Cantor

IPC: C40B30/04 ,  C12Q1/68 ,  G01N33/53 ,  B82Y15/00

Abstract: 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.

Abstract translation: 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。

公开(公告)号：US08034567B2

公开(公告)日：2011-10-11

申请号：US10655762

申请日：2003-09-05

Applicant: Charles R. Cantor ,  Chunming Ding

Inventor： Charles R. Cantor ,  Chunming Ding

IPC: C12Q1/68 ,  C12P19/34 ,  H01J49/00 ,  H01J49/40

CPC classification number: C12Q1/6851 ,  C12Q2545/107 ,  C12Q2535/125 ,  C12Q2525/186

Abstract: 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.

Abstract translation: 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。

公开(公告)号：US20100184075A1

公开(公告)日：2010-07-22

申请号：US12704043

申请日：2010-02-11

Applicant: Charles R. Cantor ,  Chunming Ding

Inventor： Charles R. Cantor ,  Chunming Ding

IPC: C12Q1/68

CPC classification number: C12Q1/6827 ,  C12Q1/6858 ,  C12Q2600/156 ,  C12Q2527/137 ,  C12Q2537/143 ,  C12Q2565/627

Abstract: 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.

Abstract translation: 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。

公开(公告)号：US07700325B2

公开(公告)日：2010-04-20

申请号：US10542043

申请日：2004-01-16

Applicant: Charles R Cantor ,  Chunming Ding

Inventor： Charles R Cantor ,  Chunming Ding

IPC: C12P19/34 ,  C12Q1/68 ,  C07H21/02

CPC classification number: C12Q1/6827 ,  C12Q1/6858 ,  C12Q2600/156 ,  C12Q2527/137 ,  C12Q2537/143 ,  C12Q2565/627

Abstract: 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.

Abstract translation: 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。