公开(公告)号：WO2016100864A1

公开(公告)日：2016-06-23

申请号：PCT/US2015/066771

申请日：2015-12-18

Applicant: THE TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK ,  BESTOR, Timothy, H. ,  JU, Jingyue ,  LI, Xiaoxu ,  RUSSO, James, J.

Inventor： BESTOR, Timothy, H. ,  JU, Jingyue ,  LI, Xiaoxu ,  RUSSO, James, J.

IPC: C07H19/167

CPC classification number: C07H19/16 ,  C07H19/167 ,  C12N9/1007 ,  C12P19/34 ,  C12Q1/6806 ,  C12Q1/6827 ,  C12Q1/6874 ,  C12Y201/01 ,  C12Q2535/101 ,  C12Q2535/122 ,  C12Q2563/101 ,  C12Q2565/631 ,  C12Q2563/167 ,  C12Q2563/107

Abstract: The present invention provides a method of determining whether cytosine residues present at a predetermined positions within a singl strand of a double stranded DNA of known sequence are methylated as well as compounds for carrying out this method. The present invention also provides a process of producing a derivative of a double-stranded DNA comprising contacting the double-stranded DNA with a CpG methyltransferase and an S-adenosylmethionine analog.

Abstract translation: 本发明提供了确定存在于已知序列的双链DNA的单链中的预定位置处的胞嘧啶残基是否被甲基化的方法以及用于实施该方法的化合物。 本发明还提供了制备双链DNA衍生物的方法，包括使双链DNA与CpG甲基转移酶和S-腺苷甲硫氨酸类似物接触。

公开(公告)号：WO2010011312A9

公开(公告)日：2010-01-28

申请号：PCT/US2009/004257

申请日：2009-07-22

Applicant: THE TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK ,  BESTOR, Timothy, H. ,  EDWARDS, John, R. ,  JU, Jingyue ,  LI, Xiaoxu

Inventor： BESTOR, Timothy, H. ,  EDWARDS, John, R. ,  JU, Jingyue ,  LI, Xiaoxu

IPC: C07H19/16 ,  A61K31/7076

Abstract: This invention provides methods of derivatizing a double-stranded DNA comprising contacting double-stranded DNA with a CpG methyltransf erase and an s-adenosylmethionine analog. This invention also provides methods of sequencing DNA to determine methylation patterns. This invention also provides neobases and methods of sequencing for methylation patterns using neobases.

公开(公告)号：WO1997011972A1

公开(公告)日：1997-04-03

申请号：PCT/US1996015576

申请日：1996-09-27

Applicant: THE TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK ,  BESTOR, Timothy, H.

Inventor： THE TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK

IPC: C07K19/00

CPC classification number: C12N15/63 ,  A01K2217/05 ,  A61K38/00 ,  C07K2319/00 ,  C07K2319/81 ,  C12N9/1007 ,  C12N15/67

Abstract: The present invention provides a chimeric protein which comprises a mutated DNA methyltransferase portion and a DNA binding protein portion that binds sufficiently close to a promoter sequence of a target gene which promoter sequence contains a methylation site, to specifically methylate the site and inhibit activity of the promoter and thus inhibit expression of the target gene. This invention also provides for a method for inhibiting the expression of a target gene which includes contacting a promoter of the target gene with the chimeric protein, so as to specifically methylate the promoter sequence of the target gene thus inhibiting expression of the target gene.

Abstract translation: 本发明提供了一种嵌合蛋白，其包含突变的DNA甲基转移酶部分和与启动子序列含有甲基化位点的靶基因的启动子序列足够接近的DNA结合蛋白部分，特异性甲基化位点并抑制其活性 启动子，从而抑制靶基因的表达。 本发明还提供了抑制靶基因表达的方法，其包括使靶基因的启动子与嵌合蛋白接触，从而特异性地甲基化靶基因的启动子序列从而抑制靶基因的表达。

公开(公告)号：WO2018187382A1

公开(公告)日：2018-10-11

申请号：PCT/US2018/025962

申请日：2018-04-03

Applicant: THE TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK ,  JU, Jingyue ,  BESTOR, Timothy, H. ,  RUSSO, James, J. ,  JOCKUSCH, Steffen ,  LI, Xiaoxu

Inventor： JU, Jingyue ,  BESTOR, Timothy, H. ,  RUSSO, James, J. ,  JOCKUSCH, Steffen ,  LI, Xiaoxu

IPC: C12Q1/68 ,  C12N9/02 ,  C12N9/10

Abstract: The subject invention provides a method of determining whether a cytosine at a predefined position within a single strand of a double-stranded DNA of known sequence is hydroxymethylated. The invention also provides a method of determining whether a cytosine at a predefined position within a single strand of a double-stranded DNA of known sequence is unmethylated. The invention further provides a method of determining whether a cytosine at a predefined position within a single strand of a double-stranded DNA of known sequence is methylated but not hydroxymethylated. The invention also provides a method of determining whether a cytosine present at a predefined position within a single strand of a double-stranded DNA of known sequence, and within a CpG site, is unmethylated.

公开(公告)号：WO2014204861A1

公开(公告)日：2014-12-24

申请号：PCT/US2014/042567

申请日：2014-06-16

Applicant: THE TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK ,  BESTOR, Timothy H. ,  JU, Jingyue ,  LI, Xiaoxu

Inventor： BESTOR, Timothy H. ,  JU, Jingyue ,  LI, Xiaoxu

IPC: C07H19/23 ,  C07H19/167 ,  C07H19/173

CPC classification number: C07H19/167 ,  C07H1/00 ,  C07H21/04 ,  C12Q1/6874 ,  C12Q2523/125 ,  C12Q2535/101 ,  C12Q2563/107 ,  C12Q2563/101

Abstract: The present invention provides a compound having the adenosylmethionine structure, wherein the sulfur atom of the methionine moiety is modified with alkene or succinimide groups, wherein R1, R2 and R3 are independently H, alkyl, aryl, C(0)NH2, C(0)R', CN, N02, C (O)R', S(0),NHR'; wherein X is 0 or NR'; wherein R' is H, alkyl or aryl; and wherein n is an integer from 1 to 8, with the proviso that, when substituent is a propene derivative, and n is 1, at least one of R1, R2, or R3 is other than H.

Abstract translation: 本发明提供了具有腺苷甲硫氨酸结构的化合物，其中甲硫氨酸部分的硫原子被烯烃或琥珀酰亚胺基团改性，其中R 1，R 2和R 3独立地为H，烷基，芳基，C（O）NH 2，C（O ）R'，CN，NO 2，C（O）R'，S（O），NHR' 其中X为0或NR'; 其中R'是H，烷基或芳基; 并且其中n是1至8的整数，条件是当取代基是丙烯衍生物，并且n是1时，R 1，R 2或R 3中的至少一个不是H.

公开(公告)号：WO2010011312A1

公开(公告)日：2010-01-28

申请号：PCT/US2009004257

申请日：2009-07-22

Applicant: UNIV COLUMBIA ,  BESTOR TIMOTHY H ,  EDWARDS JOHN R ,  JU JINGYUE ,  LI XIAOXU

Inventor： BESTOR TIMOTHY H ,  EDWARDS JOHN R ,  JU JINGYUE ,  LI XIAOXU

IPC: C07H19/16 ,  A61K31/7076

CPC classification number: C12Q1/6806 ,  C07H19/23 ,  C12Q1/6827 ,  C12Q1/6874 ,  C12Q2521/125 ,  C12Q2527/125 ,  C12Q2537/164

Abstract: This invention provides methods of derivatizing a double-stranded DNA comprising contacting double-stranded DNA with a CpG methyltransf erase and an s-adenosylmethionine analog. This invention also provides methods of sequencing DNA to determine methylation patterns. This invention also provides neobases and methods of sequencing for methylation patterns using neobases.

Abstract translation: 本发明提供衍生双链DNA的方法，包括使双链DNA与CpG甲基转移酶和S-腺苷甲硫氨酸类似物接触。 本发明还提供了测序DNA以测定甲基化模式的方法。 本发明还提供了新基因和使用新碱基测序甲基化模式的方法。

公开(公告)号：WO2003035860A1

公开(公告)日：2003-05-01

申请号：PCT/US2002/034159

申请日：2002-10-24

Applicant: THE TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK ,  BESTOR, Timothy, H.

Inventor： BESTOR, Timothy, H.

IPC: C12N9/16

CPC classification number: C12Q1/683 ,  C12Q2523/107 ,  C12Q2521/331

Abstract: This invention provides a method for detecting the presence of differential methylation between DNA from a first source and the corresponding DNA from a second source. Also provided is a method for determining the presence of a tumor suppressor gene in a DNA sample from a tumor cell.

Abstract translation: 本发明提供了一种检测来自第一来源的DNA与来自第二来源的相应DNA之间差异甲基化的存在的方法。 还提供了用于确定来自肿瘤细胞的DNA样品中肿瘤抑制基因的存在的方法。