公开(公告)号：US06268131B1

公开(公告)日：2001-07-31

申请号：US08990851

申请日：1997-12-15

Applicant: Changwon Kang ,  Young-Soo Kwon ,  Young Tae Kim ,  Hubert Köster ,  Daniel P. Little ,  Maryanne J. Little ,  Guobing Xiang ,  David M. Lough ,  Charles Cantor

Inventor： Changwon Kang ,  Young-Soo Kwon ,  Young Tae Kim ,  Hubert Köster ,  Daniel P. Little ,  Maryanne J. Little ,  Guobing Xiang ,  David M. Lough ,  Charles Cantor

IPC: C12Q168

CPC classification number: C12Q1/6872 ,  B01J2219/00317 ,  B01J2219/00387 ,  B01J2219/00527 ,  B01J2219/00585 ,  B01J2219/00596 ,  B01J2219/00605 ,  B01J2219/00612 ,  B01J2219/00621 ,  B01J2219/00626 ,  B01J2219/00637 ,  B01J2219/00648 ,  B01J2219/00659 ,  B01J2219/00689 ,  B01J2219/00691 ,  B01J2219/00702 ,  B01J2219/00722 ,  C40B40/06 ,  C40B60/14 ,  C12Q2525/143

Abstract: A mass spectrometric method for sequencing nucleic acids using RNA polymerases, including DNA-dependent and RNA-dependent RNA polymerases, is provided. The methods use a modified Sanger sequencing strategy in which RNA polymerase is used to generate a set of nested RNA transcripts obtained by base-specific chain termination. These are analyzed by mass spectrometry. A method of identifying transcriptional terminator sequences or attenuator sequences is also provided.

Abstract translation: 提供了使用RNA聚合酶对核酸进行测序的质谱法，包括DNA依赖性和RNA依赖性RNA聚合酶。 该方法使用修饰的Sanger测序策略，其中RNA聚合酶用于产生通过碱基特异性链终止获得的一组巢式RNA转录物。 这些通过质谱分析。 还提供了鉴定转录终止子序列或衰减子序列的方法。

公开(公告)号：US08467976B2

公开(公告)日：2013-06-18

申请号：US12940993

申请日：2010-11-05

Applicant: Yuk Ming Dennis Lo ,  Kwan Chee Chan ,  Wai Kwun Rossa Chiu ,  Charles Cantor

Inventor： Yuk Ming Dennis Lo ,  Kwan Chee Chan ,  Wai Kwun Rossa Chiu ,  Charles Cantor

IPC: G06F19/00 ,  C12Q1/68 ,  G11C17/00

CPC classification number: C12Q1/6876 ,  C12Q1/6827 ,  G06F19/18 ,  G06F19/22 ,  G06F19/24 ,  Y10T436/143333 ,  C12Q2537/165 ,  C12Q2535/101 ,  C12Q2527/125

Abstract: Systems, methods, and apparatus for determining at least a portion of fetal genome are provided. DNA fragments from a maternal sample (maternal and fetal DNA) can be analyzed to identify alleles at certain loci. The amounts of DNA fragments of the respective alleles at these loci can be analyzed together to determine relative amounts of the haplotypes for these loci and determine which haplotypes have been inherited from the parental genomes. Loci where the parents are a specific combination of homozygous and heterozygous can be analyzed to determine regions of the fetal genome. Reference haplotypes common in the population can be used along with the analysis of the DNA fragments of the maternal sample to determine the maternal and paternal genomes. Determination of mutations, a fractional fetal DNA concentration in a maternal sample, and a proportion of coverage of a sequencing of the maternal sample can also be provided.

Abstract translation: 提供了用于确定胎儿基因组的至少一部分的系统，方法和装置。 可以分析来自母体样品（母体和胎儿DNA）的DNA片段，以鉴定某些位点处的等位基因。 可以一起分析在这些位点处各个等位基因的DNA片段的量，以确定这些基因座的单倍型的相对量，并确定哪些单元型已经从亲代基因组遗传。 可以分析父母是纯合子和杂合子的特异性组合的位点，以确定胎儿基因组的区域。 可以在群体中常见的参考单倍型与母体样品的DNA片段的分析一起使用，以确定母体和父系的基因组。 也可以提供母体样品中突变的确定，胎儿DNA分数的分数以及母体样品测序的覆盖率。

公开(公告)号：US20110105353A1

公开(公告)日：2011-05-05

申请号：US12940993

申请日：2010-11-05

Applicant: Yuk Ming Dennis Lo ,  Kwan Chee Chan ,  Wai Kwun Rossa Chiu ,  Charles Cantor

Inventor： Yuk Ming Dennis Lo ,  Kwan Chee Chan ,  Wai Kwun Rossa Chiu ,  Charles Cantor

IPC: G01N33/53 ,  G01N33/48 ,  C12Q1/68

CPC classification number: C12Q1/6876 ,  C12Q1/6827 ,  G06F19/18 ,  G06F19/22 ,  G06F19/24 ,  Y10T436/143333 ,  C12Q2537/165 ,  C12Q2535/101 ,  C12Q2527/125

Abstract: Systems, methods, and apparatus for determining at least a portion of fetal genome are provided. DNA fragments from a maternal sample (maternal and fetal DNA) can be analyzed to identify alleles at certain loci. The amounts of DNA fragments of the respective alleles at these loci can be analyzed together to determine relative amounts of the haplotypes for these loci and determine which haplotypes have been inherited from the parental genomes. Loci where the parents are a specific combination of homozygous and heterozygous can be analyzed to determine regions of the fetal genome. Reference haplotypes common in the population can be used along with the analysis of the DNA fragments of the maternal sample to determine the maternal and paternal genomes. Determination of mutations, a fractional fetal DNA concentration in a maternal sample, and a proportion of coverage of a sequencing of the maternal sample can also be provided.

Abstract translation: 提供了用于确定胎儿基因组的至少一部分的系统，方法和装置。 可以分析来自母体样品（母体和胎儿DNA）的DNA片段，以鉴定某些位点处的等位基因。 可以一起分析在这些位点处各个等位基因的DNA片段的量，以确定这些基因座的单倍型的相对量，并确定哪些单元型已经从亲代基因组遗传。 可以分析父母是纯合子和杂合子的特异性组合的位点，以确定胎儿基因组的区域。 可以在群体中常见的参考单倍型与母体样品的DNA片段的分析一起使用，以确定母体和父系的基因组。 也可以提供母体样品中突变的确定，胎儿DNA分数的分数以及母体样品测序的覆盖率。

公开(公告)号：US20070136827A1

公开(公告)日：2007-06-14

申请号：US10535128

申请日：2003-11-14

Applicant: James Collins ,  Farren Isaacs ,  Charles Cantor ,  Daniel Dwyer

Inventor： James Collins ,  Farren Isaacs ,  Charles Cantor ,  Daniel Dwyer

IPC: A01K67/027 ,  C07H21/04 ,  C12N15/09 ,  C12N5/06

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：US20110172111A1

公开(公告)日：2011-07-14

申请号：US12852336

申请日：2010-08-06

Applicant: Charles Cantor ,  Hubert Köster

Inventor： Charles Cantor ,  Hubert Köster

IPC: C40B30/04

CPC classification number: C12Q1/6872 ,  C12Q1/6874 ,  C12Q2565/501 ,  C12Q2531/113 ,  C12Q2521/525 ,  C12Q2565/627 ,  C12Q2531/119 ,  C12Q2523/301 ,  C12Q2531/137 ,  C12Q2521/301 ,  C12Q2531/149

Abstract: This invention relates to methods for detecting and sequencing target nucleic acid sequences, to mass modified nucleic acid probes and arrays of probes useful in these methods, and to kits and systems which contain these probes. Useful methods involve hybridizing the nucleic acids or nucleic acids which represent complementary or homologous sequences of the target to an array of nucleic acid probes. These probes comprise a single-stranded portion, an optional double-stranded portion and a variable sequence within the single-stranded portion. The molecular weights of the hybridized nucleic acids of the set can be determined by mass spectroscopy, and the sequence of the target determined from the molecular weights of the fragments. Nucleic acids whose sequences can be determined include DNA or RNA in biological samples such as patient biopsies and environmental samples. Probes may be fixed to a solid support such as a hybridization chip to facilitate automated molecular weight analysis and identification of the target sequence.

Abstract translation: 本发明涉及用于检测和测序靶核酸序列，批量修饰的核酸探针和可用于这些方法的探针阵列的方法，以及含有这些探针的试剂盒和系统。 有用的方法包括将代表靶的互补或同源序列的核酸或核酸与核酸探针阵列进行杂交。 这些探针包括在单链部分内的单链部分，任选的双链部分和可变序列。 该组的杂交核酸的分子量可以通过质谱法测定，并且靶标的序列由片段的分子量确定。 可以确定其序列的核酸包括生物样品中的DNA或RNA，例如患者活组织检查和环境样品。 探针可以固定在固体支持物例如杂交芯片上以促进自动化分子量分析和靶序列的鉴定。

公开(公告)号：US20100047179A1

公开(公告)日：2010-02-25

申请号：US12447368

申请日：2007-10-26

Applicant: Vadim Demidov ,  Natalia Broude ,  Charles Cantor ,  William Evans

Inventor： Vadim Demidov ,  Natalia Broude ,  Charles Cantor ,  William Evans

IPC: A61K48/00 ,  C07K2/00 ,  A61K38/02 ,  A61K39/00 ,  A61K39/02 ,  A61K38/54 ,  A61P25/00 ,  A61P25/28 ,  A61P29/00 ,  A61K9/127 ,  A61K9/14 ,  A61K31/7088 ,  A61K49/00

CPC classification number: A61K49/0056 ,  A61K47/56 ,  A61K47/642 ,  A61K47/6817 ,  A61K47/6819 ,  A61K47/6821 ,  A61K47/6823 ,  A61K47/6825 ,  A61K47/6827 ,  A61K47/6829 ,  A61K49/0045

Abstract: The present invention is directed to compositions and methods for the production of split-biomolecular conjugates for the directed targeting of nucleic acids and polypeptides. More preferably, the compositions and methods allow for the use of the split biomolecular conjugates for the treatment of diseases, malignancies, disorders and screening. In some embodiments, the split biomolecular conjugates comprise split effector protein fragments conjugated to a probe, and interaction of both probes with a target nucleic acid or target polypeptide, such as a pathogenic nucleic acid sequence or pathogenic protein, brings a the split-effector fragments together to facilitate the reassembly of the effector molecule. Depending on the effector molecule, the protein complementation results in a cellular effect, in particular for the treatment of diseases, malignancies and disorders.

Abstract translation: 本发明涉及用于产生用于核酸和多肽的定向靶向的分裂生物分子缀合物的组合物和方法。 更优选地，组合物和方法允许使用分裂的生物分子缀合物来治疗疾病，恶性肿瘤，病症和筛选。 在一些实施方案中，分裂的生物分子缀合物包含与探针缀合的分裂效应子蛋白片段，以及两种探针与靶核酸或靶多肽（例如致病性核酸序列或致病性蛋白质）的相互作用带来分裂效应物片段 一起以促进效应分子的重组。 取决于效应分子，蛋白质互补导致细胞效应，特别是用于治疗疾病，恶性肿瘤和病症。

公开(公告)号：US20060094014A1

公开(公告)日：2006-05-04

申请号：US10529122

申请日：2003-10-09

Applicant: Charles Cantor ,  Natalia Broude ,  Carlos Witte-Hoffmann

Inventor： Charles Cantor ,  Natalia Broude ,  Carlos Witte-Hoffmann

IPC: C12Q1/68 ,  C07H21/00 ,  A61K49/00

CPC classification number: C12Q1/6818 ,  C12Q1/6813 ,  C12Q2563/131 ,  C12Q2561/107

Abstract: The present invention is directed to novel methods for in vitro and in vivo detection of target nucleic acid molecules, including DNA and RNA targets, as well as nucleic acid analogues. The present invention is based on protein complementation, in which two individual polypeptides are inactive. When the two inactive polypeptide fragment are brought in close proximity during hybridization to a target nucleic acid, they re-associate into an active, detectable protein.

Abstract translation: 本发明涉及用于靶核酸分子（包括DNA和RNA靶标）以及核酸类似物的体外和体内检测的新方法。 本发明基于蛋白质互补，其中两个单独的多肽是无活性的。 当两个无活性多肽片段在与靶核酸杂交期间紧密接近时，它们重新连接成活性的可检测蛋白质。

公开(公告)号：US20050014158A1

公开(公告)日：2005-01-20

申请号：US10607806

申请日：2003-06-27

Applicant: Gail Adam ,  Maria Langdown ,  Mikhail Denissenko ,  Edward Dennis ,  Charles Cantor ,  Byron Rubin

Inventor： Gail Adam ,  Maria Langdown ,  Mikhail Denissenko ,  Edward Dennis ,  Charles Cantor ,  Byron Rubin

IPC: A61B20060101 ,  A61K31/7088 ,  A61K38/46 ,  A61K45/00 ,  A61K48/00 ,  C12Q1/00 ,  C12Q1/34 ,  C12Q1/44 ,  C12Q1/68 ,  G01N33/53 ,  G01N33/564 ,  G01N33/566 ,  G01N33/68 ,  G01N33/92

CPC classification number: G01N33/566 ,  G01N33/564 ,  G01N33/6893 ,  G01N2500/20 ,  G01N2800/042

Abstract: Provided herein are methods for prognosing and diagnosing fat deposition and related disorders (e.g., obesity and non-insulin diabetes dependent mellitus (NIDDM)) in a subject, reagents and kits for carrying out the methods, methods for identifying candidate therapeutics for reducing fat deposition and related disorders, and therapeutic methods for reducing fat deposition or treating fat deposition related disorders in a subject. These embodiments are based in part upon an analysis of polymorphic variations of the nucleic acid set forth in SEQ ID NO:1.

Abstract translation: 本文提供了用于预测和诊断受试者的脂肪沉积和相关疾病（例如，肥胖和非胰岛素糖尿病依赖性细胞（NIDDM））的方法，用于实施该方法的试剂和试剂盒，用于鉴定用于减少脂肪沉积的候选治疗剂的方法 和相关疾病，以及用于减少受试者中脂肪沉积或治疗脂肪沉积相关疾病的治疗方法。 这些实施方案部分地基于对SEQ ID NO：1所示的核酸的多态变异的分析。

公开(公告)号：US06284497B1

公开(公告)日：2001-09-04

申请号：US09287781

申请日：1999-04-08

Applicant: Chandran R. Sabanayagam ,  Takeshi Sano ,  John Misasi ,  Anson Hatch ,  Charles Cantor

Inventor： Chandran R. Sabanayagam ,  Takeshi Sano ,  John Misasi ,  Anson Hatch ,  Charles Cantor

IPC: C12P1934

CPC classification number: C07H21/00 ,  B01J2219/00527 ,  B01J2219/00529 ,  B01J2219/00596 ,  B01J2219/00608 ,  B01J2219/0061 ,  B01J2219/00612 ,  B01J2219/0063 ,  B01J2219/00637 ,  B01J2219/00659 ,  B01J2219/00722 ,  C07B2200/11 ,  C12P19/34 ,  C12Q1/6846 ,  C12Q1/6853 ,  C40B40/06 ,  Y10T436/143333 ,  C12Q2565/537 ,  C12Q2531/125 ,  C12Q2531/101

Abstract: The present invention generally relates to high density nucleic acid arrays and methods of synthesizing nucleic acid sequences on a solid surface. Specifically, the present invention contemplates the use of stabilized nucleic acid primer sequences immobilized on solid surfaces, and circular nucleic acid sequence templates combined with the use of isothermal rolling circle amplification to thereby increase nucleic acid sequence concentrations in a sample or on an array of nucleic acid sequences.

Abstract translation: 本发明一般涉及高密度核酸阵列和在固体表面上合成核酸序列的方法。 具体地，本发明考虑使用固定在固体表面上的稳定的核酸引物序列，以及环状核酸序列模板结合使用等温滚环扩增从而增加样品或核酸阵列上的核酸序列浓度 酸序列。

公开(公告)号：US06225061B1

公开(公告)日：2001-05-01

申请号：US09266409

申请日：1999-03-10

Applicant: Thomas Becker ,  Hubert Köster ,  Charles Cantor

Inventor： Thomas Becker ,  Hubert Köster ,  Charles Cantor

IPC: C12Q168

CPC classification number: B01J19/16 ,  B01J2219/00317 ,  B01J2219/00367 ,  B01J2219/00378 ,  B01J2219/00495 ,  B01J2219/00603 ,  B01J2219/0068 ,  C40B60/14 ,  G01N2035/00287 ,  Y10T436/11 ,  Y10T436/25375

Abstract: An open system is provided for performing a submicroliter reaction. An open system can contain a solid support having a target site for performing the reaction; a liquid dispensing system such as a nanoliter dispensing pipette for dispensing a submicroliter amount of a liquid to the target site; a temperature controlling device for regulating the temperature of the support; and means for controlling the amount of liquid dispensed, which corresponds to the amount of liquid that evaporates from the target site. Also provided is an open system, including a solid support having a target site; a liquid dispensing system, which can dispense a liquid to the target site; a temperature controlling system, which regulates the temperature of the solid support; and an interface, which regulates an amount of liquid dispensed from the liquid dispensing system. Also provided is a method for performing a reaction in a submicroliter volume in an unsealed environment by dispensing a submicroliter volume of liquid onto the surface of a support; monitoring the temperature of the support; monitoring an amount or rate of evaporation of the liquid; and dispensing to the surface of the support a further amount of the liquid, which corresponds to the amount lost from the support due to evaporation, thereby maintaining the reaction volume at a predetermined volume throughout the course of the reaction. A method also is provided for maintaining a volume of a reaction mixture, which can be one of a plurality of reaction mixtures, on a solid support in an unsealed environment by monitoring the rate of evaporation of a liquid from the reaction mixture; and dispensing into the reaction mixture an amount of liquid that corresponds to the amount that evaporates.

Abstract translation: 提供了用于进行亚微米级反应的开放系统。 开放系统可以含有具有用于进行反应的靶位点的固体支持物; 液体分配系统，例如用于将目标部位的微量剂量的液体分配的纳升分配移液管; 用于调节支撑件的温度的温度控制装置; 以及用于控制分配的液体量的装置，其对应于从目标部位蒸发的液体的量。 还提供了一种开放系统，包括具有目标地点的固体支撑物; 液体分配系统，其可以将液体分配到目标部位; 温度控制系统，其调节固体支持物的温度; 以及界面，其调节从液体分配系统分配的液体的量。 还提供了一种在非密封环境中通过将亚微米级体积的液体分配到载体的表面上来进行亚微米体积的反应的方法; 监测支架的温度; 监测液体的蒸发量或速率; 并且向支撑体的表面分配更多量的液体，其对应于由于蒸发而从支撑物损失的量，从而在反应过程中将反应体积保持在预定体积。 还提供了一种方法，用于通过监测来自反应混合物的液体的蒸发速率来保持反应混合物的体积，反应混合物可以是多个反应混合物中的一种，在固体支持物上在未密封环境中; 并向反应混合物中分配一定量的与蒸发量对应的液体。