公开(公告)号：WO2015167959A1

公开(公告)日：2015-11-05

申请号：PCT/US2015/027541

申请日：2015-04-24

Applicant: SIGMA-ALDRICH CO. LLC

Inventor： DAVIS, Gregory D. ,  KANG, Qiaohua

IPC: C12Q1/68 ,  C12Q1/02

CPC classification number: C12Q1/6883 ,  C12N15/907 ,  C12N2510/00 ,  C12Q1/6886 ,  C12Q2600/118 ,  C12Q2600/154 ,  C12Q2600/166

Abstract: The present disclosure provides genetically engineered cell lines comprising chromosomally integrated synthetic sequences having predetermined epigenetic modifications, wherein a predetermined epigenetic modification is correlated with a known diagnosis, prognosis or level of sensitivity to a disease treatment. Also provided are kits comprising said epigenetically modified synthetic nucleic acids or cells comprising said epigenetically modified synthetic nucleic acids that can be used as reference standards for predicting responsiveness to therapeutic treatments, diagnosing diseases, or predicting disease prognosis.

Abstract translation: 本公开提供了包含具有预定表观遗传修饰的染色体整合的合成序列的遗传工程改造的细胞系，其中预定的表观遗传修饰与已知的疾病治疗的敏感性的诊断，预后或水平相关。 还提供了包含所述表观遗传修饰的合成核酸或包含所述表观遗传修饰的合成核酸的细胞的试剂盒，其可以用作预测对治疗性治疗的响应性，诊断疾病或预测疾病预后的参考标准。

公开(公告)号：WO2016210271A1

公开(公告)日：2016-12-29

申请号：PCT/US2016/039261

申请日：2016-06-24

Applicant: SIGMA-ALDRICH CO. LLC

Inventor： DAVIS, Gregory D. ,  JI, Qingzhou ,  KREADER, Carol A.

IPC: A61K45/00 ,  A61K48/00 ,  C07K19/00

CPC classification number: C12N15/907 ,  C07K14/43595 ,  C07K14/4703 ,  C07K2319/00 ,  C07K2319/60 ,  C12N9/22

Abstract: Fusion protein comprising a programmable DNA modification protein and a cell cycle regulated protein, and methods of using the fusion protein to modify chromosomal sequences and/or regulate gene expression in a cell cycle dependent manner.

Abstract translation: 包含可编程DNA修饰蛋白和细胞周期调节蛋白的融合蛋白，以及使用所述融合蛋白以细胞周期依赖性方式修饰染色体序列和/或调节基因表达的方法。

公开(公告)号：WO2019014230A1

公开(公告)日：2019-01-17

申请号：PCT/US2018/041454

申请日：2018-07-10

Applicant: SIGMA-ALDRICH CO. LLC

Inventor： CHEN, Fuqiang ,  DING, Xiao ,  FENG, Yongmei ,  DAVIS, Gregory D.

IPC: C12N15/90 ,  C12N15/85 ,  C12N15/86 ,  C12N15/11 ,  C12N9/96

Abstract: Compositions and methods for using nucleosome interacting protein domains to increase accessibility of programmable DNA modification proteins to target chromosomal sequences, thereby increasing efficiency of targeted genome/epigenetic modification in eukaryotic cells.

公开(公告)号：WO2017053762A1

公开(公告)日：2017-03-30

申请号：PCT/US2016/053386

申请日：2016-09-23

Applicant: SIGMA-ALDRICH CO. LLC

Inventor： DAVIS, Gregory D. ,  PALHAN, Vikas ,  KREADER, Carol A.

IPC: C12Q1/68 ,  C07K16/40

CPC classification number: C07K16/40 ,  C12Q1/6827 ,  C12Q2521/301 ,  C12Q2521/501 ,  C12Q2525/307 ,  C12Q2531/125 ,  C12Q2533/107

Abstract: The present disclosure provides reagents and methods for molecular proximity detection of specific endogenous nucleic acids in situ using RNA-guided nucleic acid binding proteins.

Abstract translation: 本公开提供了使用RNA引导的核酸结合蛋白原位分子亲和检测特异性内源核酸的试剂和方法。

公开(公告)号：WO2014089290A1

公开(公告)日：2014-06-12

申请号：PCT/US2013/073307

申请日：2013-12-05

Applicant: SIGMA-ALDRICH CO. LLC ,  CHEN, Fuqiang ,  DAVIS, Gregory D. ,  KANG, Qiaohua ,  KNIGHT, Scott W.

Inventor： CHEN, Fuqiang ,  DAVIS, Gregory D. ,  KANG, Qiaohua ,  KNIGHT, Scott W.

IPC: A61K45/00

CPC classification number: C12N15/907 ,  A61K38/00 ,  C07K7/06 ,  C07K14/463 ,  C07K2319/09 ,  C07K2319/10 ,  C07K2319/81 ,  C12N7/00 ,  C12N9/22 ,  C12N9/96 ,  C12N15/102 ,  C12N15/11 ,  C12N15/63 ,  C12N15/67 ,  C12N15/85 ,  C12N15/86 ,  C12N2310/3513 ,  C12N2750/14143 ,  C12N2800/22 ,  C12N2800/80 ,  C12Y301/00 ,  C12Y301/21004

Abstract: The present invention provides RNA-guided endonucleases, which are engineered for expression in eukaryotic cells or embryos, and methods of using the RNA-guided endonuclease for targeted genome modification in in eukaryotic cells or embryos. Also provided are fusion proteins, wherein each fusion protein comprises a CRISPR/Cas-like protein or fragment thereof and an effector domain. The effector domain can be a cleavage domain, an epigenetic modification domain, a transcriptional activation domain, or a transcriptional repressor domain. Also provided are methods for using the fusion proteins to modify a chromosomal sequence or regulate expression of a chromosomal sequence.

Abstract translation: 本发明提供了用于在真核细胞或胚胎中表达的RNA引导的内切核酸酶，以及使用RNA引导的内切核酸酶在真核细胞或胚胎中靶向基因组修饰的方法。 还提供融合蛋白，其中每个融合蛋白包含CRISPR / Cas样蛋白或其片段和效应结构域。 效应结构域可以是切割结构域，表观遗传修饰结构域，转录激活结构域或转录阻遏物结构域。 还提供了使用融合蛋白修饰染色体序列或调节染色体序列表达的方法。