公开(公告)号：US20240167018A1

公开(公告)日：2024-05-23

申请号：US18317248

申请日：2023-05-15

申请人： The Broad Institute, Inc. ,  Massachusetts Institute of Technology ,  Children's Medical Center Corporation

发明人： Daniel E. Bauer ,  Stuart H. Orkin ,  Neville Espi Sanjana ,  Ophir Shalem ,  Jason Wright ,  Feng Zhang

IPC分类号： C12N15/10

CPC分类号： C12N15/1079 ,  C12N15/102 ,  C12N15/1075 ,  C12N15/1082

摘要： The application relates to a deep scanning mutagenesis library to interrogate phenotypic changes in a population of cells comprising a plurality of CRISPR-Cas system guide RNAs targeting genomic sequences within at least one continuous genomic region, wherein the guide RNAs target at least 100 genomic sequences upstream of a PAM sequence for every 1000 base pairs within the continuous genomic region and methods for their use.

公开(公告)号：US20240102004A1

公开(公告)日：2024-03-28

申请号：US18345958

申请日：2023-06-30

申请人： THE BROAD INSTITUTE, INC. ,  MASSACHUSETTS INSTITUTE OF TECHNOLOGY ,  CHILDREN'S MEDICAL CENTER CORPORATION

发明人： Daniel E. Bauer ,  Stuart H. Orkin ,  Neville Espi Sanjana ,  Ophir Shalem ,  Jason Wright ,  Feng Zhang

IPC分类号： C12N15/10

CPC分类号： C12N15/1079 ,  C12N15/102 ,  C12N15/1075 ,  C12N15/1082

摘要： The application relates to a deep scanning mutagenesis library to interrogate phenotypic changes in a population of cells comprising a plurality of CRISPR-Cas system guide RNAs targeting genomic sequences within at least one continuous genomic region, wherein the guide RNAs target at least 100 genomic sequences upstream of a PAM sequence for every 1000 base pairs within the continuous genomic region and methods for their use.

公开(公告)号：US11685917B2

公开(公告)日：2023-06-27

申请号：US15807007

申请日：2017-11-08

申请人： THE BROAD INSTITUTE, INC. ,  MASSACHUSETTS INSTITUTE OF TECHNOLOGY ,  CHILDREN'S MEDICAL CENTER CORPORATION

发明人： Daniel E. Bauer ,  Stuart H. Orkin ,  Neville Espi Sanjana ,  Ophir Shalem ,  Jason Wright ,  Feng Zhang

IPC分类号： C12N15/10

CPC分类号： C12N15/1079 ,  C12N15/102 ,  C12N15/1075 ,  C12N15/1082

摘要： The application relates to a deep scanning mutagenesis library to interrogate phenotypic changes in a population of cells comprising a plurality of CRISPR-Cas system guide RNAs targeting genomic sequences within at least one continuous genomic region, wherein the guide RNAs target at least 100 genomic sequences upstream of a PAM sequence for every 1000 base pairs within the continuous genomic region and methods for their use.

公开(公告)号：US11572543B2

公开(公告)日：2023-02-07

申请号：US15572523

申请日：2016-05-06

申请人： The Children's Medical Center Corporation ,  The Broad Institute, Inc. ,  Massachusetts Institute of Technology

发明人： Daniel E. Bauer ,  Stuart H. Orkin ,  Neville Sanjana ,  Ophir Shalem ,  Feng Zhang

IPC分类号： C12N5/078 ,  C12N15/10 ,  C12N9/22 ,  C12N15/11 ,  C12N15/86

摘要： Provided herein are nucleic acid molecules that target the BCL11A enhancer functional regions, compositions comprising the nucleic acid molecules and methods for increasing fetal hemoglobin levels in a cell by disrupting BCL11A expression at the genomic level. Also provided herein are methods and compositions relating to the treatment of hemoglobinopathies by reinduction of fetal hemoglobin levels. In particular, the nucleic acid molecules target the +62, +58, and/or the +55 enhancer functional regions.

公开(公告)号：US20180171297A1

公开(公告)日：2018-06-21

申请号：US15572523

申请日：2016-05-06

申请人： The Children's Medical Center Corporation ,  The Broad Institute, Inc. ,  Massachusetts Institute of Technology

发明人： Daniel E. Bauer ,  Stuart H. Orkin ,  Neville Sanjana ,  Ophir Shalem ,  Feng Zhang

IPC分类号： C12N5/078 ,  C12N15/11 ,  C12N15/86 ,  C12N9/22

CPC分类号： C12N5/0641 ,  C12N9/22 ,  C12N15/102 ,  C12N15/11 ,  C12N15/86 ,  C12N2310/20 ,  C12N2510/00 ,  C12N2740/15041

摘要： Provided herein are nucleic acid molecules that target the BCL11A enhancer functional regions, compositions comprising the nucleic acid molecules and methods for increasing fetal hemoglobin levels in a cell by disrupting BCL11A expression at the genomic level. Also provided herein are methods and compositions relating to the treatment of hemoglobinopathies by reinduction of fetal hemoglobin levels. In particular, the nucleic acid molecules target the +62, +58, and/or the +55 enhancer functional regions.

公开(公告)号：US20180119138A1

公开(公告)日：2018-05-03

申请号：US15807007

申请日：2017-11-08

申请人： THE BROAD INSTITUTE INC. ,  MASSACHUSETTS INSTITUTE OF TECHNOLOGY ,  CHILDREN'S MEDICAL CENTER CORPORATION

发明人： Daniel E. Bauer ,  Stuart H. Orkin ,  Neville Espi Sanjana ,  Ophir Shalem ,  Jason Wright ,  Feng Zhang

IPC分类号： C12N15/10

CPC分类号： C12N15/1079 ,  C12N15/102 ,  C12N15/1075 ,  C12N15/1082

摘要： The application relates to a deep scanning mutagenesis library to interrogate phenotypic changes in a population of cells comprising a plurality of CRISPR-Cas system guide RNAs targeting genomic sequences within at least one continuous genomic region, wherein the guide RNAs target at least 100 genomic sequences upstream of a PAM sequence for every 1000 base pairs within the continuous genomic region and methods for their use.

公开(公告)号：US20210348143A1

公开(公告)日：2021-11-11

申请号：US17239780

申请日：2021-04-26

申请人： Children's Medical Center Corporation ,  Sangamo Therapeutics, Inc.

发明人： Stuart H. Orkin ,  Andreas Reik ,  Fyodor Urnov

IPC分类号： C12N9/22 ,  C12N15/85 ,  A61K35/12 ,  C12N15/113 ,  C07K14/47 ,  A61K38/46 ,  A61K35/28

摘要： The present disclosure is in the field of genome engineering, particularly targeted modification of the genome of a hematopoietic cell.

公开(公告)号：US11542493B2

公开(公告)日：2023-01-03

申请号：US16573389

申请日：2019-09-17

申请人： The Children's Medical Center Corporation

发明人： Stuart H. Orkin ,  Daniel E. Bauer ,  Jian Xu

IPC分类号： C12N15/63 ,  A61K35/28 ,  C12N5/078 ,  C12N15/12 ,  C12N9/16 ,  C12N15/01 ,  C07K14/47 ,  C07K14/805 ,  C12N15/10 ,  A61K35/12 ,  A61K38/46 ,  C12N9/22

摘要： Provided herein are methods and compositions for increasing fetal hemoglobin levels in a cell by disrupting BCL11A expression at the genomic level. Also provided herein are methods and compositions relating to the treatment of hemoglobinopathies by reinduction of fetal hemoglobin levels.

公开(公告)号：US10472619B2

公开(公告)日：2019-11-12

申请号：US15816083

申请日：2017-11-17

申请人： The Children's Medical Center Corporation

发明人： Stuart H. Orkin ,  Daniel E. Bauer ,  Jian Xu

IPC分类号： C12N15/12 ,  A61K35/28 ,  C12N5/078 ,  C12N15/01 ,  C07K14/805 ,  C12N15/10 ,  C12N15/63 ,  C07K14/47 ,  A61K35/12 ,  A61K38/46 ,  C12N9/22

摘要： Provided herein are methods and compositions for increasing fetal hemoglobin levels in a cell by disrupting BCL11A expression at the genomic level. Also provided herein are methods and compositions relating to the treatment of hemoglobinopathies by reinduction of fetal hemoglobin levels.

公开(公告)号：US20140271657A1

公开(公告)日：2014-09-18

申请号：US14351386

申请日：2012-10-12

申请人： CHILDREN'S MEDICAL CENTER CORPORATION

发明人： Stuart H. Orkin ,  Jian Xu ,  Peng Cong

IPC分类号： A61K39/395 ,  A61K35/28 ,  A61K31/167 ,  C12N15/113 ,  A61K31/706

CPC分类号： A61K39/3955 ,  A61K31/167 ,  A61K31/706 ,  A61K31/7105 ,  A61K35/28 ,  A61K45/06 ,  A61K2035/124 ,  C12N15/113 ,  C12N2310/11 ,  C12N2310/14 ,  C12N2310/16 ,  C12N2320/31

摘要： Provided herein are compositions and methods for increasing fetal hemoglobin expression (HbF) for the treatment and/or amelioration of the symptoms of a hemoglobinpathy in a mammal. The compositions comprise a combination of one or more inhibitors of BCL11A expression or activity with epigenetic modifiers, such as inhibitors of DNA methylation and/or one or more inhibitors of histone deacetylases.

摘要翻译： 本文提供了用于增加胎儿血红蛋白表达（HbF）用于治疗和/或改善哺乳动物血红蛋白病症状的组合物和方法。 组合物包含一种或多种BCL11A表达或活性抑制剂与表观遗传调节剂（例如DNA甲基化抑制剂）和/或一种或多种组蛋白脱乙酰酶抑制剂的组合。