公开(公告)号：US20240319173A1

公开(公告)日：2024-09-26

申请号：US18613041

申请日：2024-03-21

Applicant: Wisconsin Alumni Research Foundation

Inventor： James Thomson ,  Jue Zhang

IPC: G01N33/50 ,  A61K31/137 ,  A61K31/202 ,  A61K31/365 ,  A61K31/40 ,  A61K31/4166 ,  A61K31/47 ,  A61K31/51 ,  A61K31/519 ,  A61K31/55 ,  A61K31/56 ,  A61K31/63 ,  A61K31/685 ,  C12N5/071 ,  C12P3/00

CPC classification number: G01N33/5073 ,  A61K31/137 ,  A61K31/202 ,  A61K31/365 ,  A61K31/40 ,  A61K31/4166 ,  A61K31/47 ,  A61K31/51 ,  A61K31/519 ,  A61K31/55 ,  A61K31/56 ,  A61K31/63 ,  A61K31/685 ,  C12N5/069 ,  C12P3/00 ,  C12N2506/45 ,  C12N2510/00

Abstract: The present disclosure provides reagents and methods for identifying compounds that promote arterial endothelial cell differentiation and nitric oxide production therefrom. Pharmaceutical compositions comprising compounds identified thereby are provided as are therapeutic methods using these pharmaceutical compositions for treating neural and cardiovascular diseases and disorders associated with deficient or disrupted nitric oxide production in arterial endothelial cells.

公开(公告)号：US20160032287A1

公开(公告)日：2016-02-04

申请号：US14822099

申请日：2015-08-10

Applicant: Wisconsin Alumni Research Foundation

Inventor： Srikumar Sengupta ,  James Thomson

IPC: C12N15/113 ,  C12N5/071

CPC classification number: C12N15/113 ,  A61K35/407 ,  A61K35/545 ,  A61K38/38 ,  A61K38/44 ,  A61K38/45 ,  A61K38/57 ,  C12N5/067 ,  C12N5/0672 ,  C12N15/111 ,  C12N2310/141 ,  C12N2320/30 ,  C12N2501/65 ,  C12N2510/00 ,  C12Y114/13017 ,  C12Y114/14001 ,  C12Y206/01005 ,  G01N33/5014

Abstract: A method for producing mature hepatocytes having functional hepatic enzyme activity from human pluripotent cells is disclosed. The method includes the step of transferring an external vector comprising the DNA sequence coding for a microRNA having the seed sequence of the microRNA miR-122, the DNA sequence coding for a microRNA having the seed sequence of the microRNA miR-let-7c, a microRNA having the seed sequence of the microRNA miR-122, a microRNA having the seed sequence of the microRNA miR-let-7c, or a combination thereof into one or more fetal hepatocytes. The resulting cells differentiate into mature hepatocytes that exhibit functional hepatic enzyme activity, and can be used in drug metabolism and toxicity testing, in the study of viruses that target hepatic tissue, and as therapeutics.A related method of maintaining the functional hepatic enzyme activity of primary hepatocytes over time is also disclosed. The method includes the step of transferring an external vector comprising the DNA sequence coding for a microRNA having the seed sequence of the microRNA miR-122 into one or more cultured primary hepatocytes.

公开(公告)号：US09127253B2

公开(公告)日：2015-09-08

申请号：US13772802

申请日：2013-02-21

Applicant: Wisconsin Alumni Research Foundation

Inventor： Srikumar Sengupta ,  James Thomson

IPC: C12N15/00 ,  C12N5/071 ,  A61K35/407 ,  C12N15/11 ,  C12N15/113 ,  A61K35/545 ,  G01N33/50 ,  A61K38/38 ,  A61K38/44 ,  A61K38/45 ,  A61K38/57

CPC classification number: C12N15/113 ,  A61K35/407 ,  A61K35/545 ,  A61K38/38 ,  A61K38/44 ,  A61K38/45 ,  A61K38/57 ,  C12N5/067 ,  C12N5/0672 ,  C12N15/111 ,  C12N2310/141 ,  C12N2320/30 ,  C12N2501/65 ,  C12N2510/00 ,  C12Y114/13017 ,  C12Y114/14001 ,  C12Y206/01005 ,  G01N33/5014

Abstract: A method for producing mature hepatocytes having functional hepatic enzyme activity from human pluripotent cells is disclosed. The method includes the step of transferring an external vector that includes a microRNA having the seed sequence of the microRNA miR-122, a DNA sequence coding for such a microRNA, a microRNA having the seed sequence of the microRNA miR-let-7c, a DNA sequence coding for such a microRNA, or a combination these, into one or more fetal hepatocytes. The resulting cells differentiate into mature hepatocytes that exhibit functional hepatic enzyme activity, and that can be used in drug metabolism and toxicity testing, in the study of viruses that target hepatic tissue, and as therapeutics.

Abstract translation: 公开了一种从人多能细胞产生具有功能性肝酶活性的成熟肝细胞的方法。 该方法包括转移包含具有微小RNA miR-122的种子序列的微小RNA的外部载体的步骤，编码这种微小RNA的DNA序列，具有微小RNA miR-let-7c的种子序列的微小RNA， 编码这种微小RNA的DNA序列，或这些的组合，形成一个或多个胎儿肝细胞。 所产生的细胞分化成具有功能性肝酶活性的成熟肝细胞，并且可用于药物代谢和毒性试验，用于靶向肝组织的病毒的研究以及作为治疗剂。

公开(公告)号：US20140349405A1

公开(公告)日：2014-11-27

申请号：US14285252

申请日：2014-05-22

Applicant: NORTHWESTERN UNIVERSITY ,  WISCONSIN ALUMNI RESEARCH FOUNDATION

Inventor： Erik J. Sontheimer ,  Yan Zhang ,  Alfonso Mondragon ,  Rakhi Rajan ,  James Thomson ,  Zhonggang Hou

IPC: C12N15/85 ,  C12N9/22

CPC classification number: C12N15/85 ,  C07K14/22 ,  C07K2319/20 ,  C12N9/22 ,  C12N15/63 ,  C12N15/907

Abstract: Disclosed are components and methods for RNA-directed DNA cleavage and gene editing. The components include and the methods utilize a Cas9 protein from Neisseria and one or more RNA molecules in order to direct the Cas9 protein to bind to and optionally cleave or nick a target sequence.

Abstract translation: 公开的是用于RNA指导的DNA切割和基因编辑的组分和方法。 组分包括并且该方法利用来自奈瑟球菌的Cas9蛋白和一种或多种RNA分子，以引导Cas9蛋白结合并任选地切割或切割靶序列。

公开(公告)号：US20230113074A1

公开(公告)日：2023-04-13

申请号：US17963806

申请日：2022-10-11

Applicant: Wisconsin Alumni Research Foundation

Inventor： Srikumar Sengupta ,  James Thomson

IPC: C12N5/0735

Abstract: This disclosure relates generally to methods for generating small hepatocyte progenitor cells (SHPCs) and hematopoietic progenitor cells (HPCs) from human embryonic stem cells, and hematopoietic progenitor cells from primary human endothelial cells and cell lines populations of small hepatocyte progenitor cells and hematopoietic progenitor cells, and uses thereof.

公开(公告)号：US20190330654A1

公开(公告)日：2019-10-31

申请号：US16209722

申请日：2018-12-04

Applicant: Wisconsin Alumni Research Foundation

Inventor： James Thomson ,  Junying Yu

IPC: C12N15/85 ,  C12N5/074

Abstract: Methods for reprogramming primate somatic cells to pluripotency using an episomal vector that does not encode an infectious virus are disclosed. Pluripotent cells produced in the methods are also disclosed.

公开(公告)号：US09512428B2

公开(公告)日：2016-12-06

申请号：US14822099

申请日：2015-08-10

Applicant: Wisconsin Alumni Research Foundation

Inventor： Srikumar Sengupta ,  James Thomson

IPC: C12N15/11 ,  C12N15/113 ,  C12N5/071 ,  A61K35/407 ,  A61K35/545 ,  G01N33/50 ,  A61K38/38 ,  A61K38/44 ,  A61K38/45 ,  A61K38/57

CPC classification number: C12N15/113 ,  A61K35/407 ,  A61K35/545 ,  A61K38/38 ,  A61K38/44 ,  A61K38/45 ,  A61K38/57 ,  C12N5/067 ,  C12N5/0672 ,  C12N15/111 ,  C12N2310/141 ,  C12N2320/30 ,  C12N2501/65 ,  C12N2510/00 ,  C12Y114/13017 ,  C12Y114/14001 ,  C12Y206/01005 ,  G01N33/5014

Abstract: A method for producing mature hepatocytes having functional hepatic enzyme activity from human pluripotent cells is disclosed. The method includes the step of transferring an external vector comprising the DNA sequence coding for a microRNA having the seed sequence of the microRNA miR-122, the DNA sequence coding for a microRNA having the seed sequence of the microRNA miR-let-7c, a microRNA having the seed sequence of the microRNA miR-122, a microRNA having the seed sequence of the microRNA miR-let-7c, or a combination thereof into one or more fetal hepatocytes. The resulting cells differentiate into mature hepatocytes that exhibit functional hepatic enzyme activity, and can be used in drug metabolism and toxicity testing, in the study of viruses that target hepatic tissue, and as therapeutics.A related method of maintaining the functional hepatic enzyme activity of primary hepatocytes over time is also disclosed. The method includes the step of transferring an external vector comprising the DNA sequence coding for a microRNA having the seed sequence of the microRNA miR-122 into one or more cultured primary hepatocytes.

Abstract translation: 还公开了维持原代肝细胞功能性肝酶活性的相关方法。 该方法包括将包含编码具有微小RNA miR-122的种子序列的微小RNA的DNA序列的外部载体转移到一个或多个培养的原代肝细胞中的步骤。

公开(公告)号：US20240156963A1

公开(公告)日：2024-05-16

申请号：US18302636

申请日：2023-04-18

Applicant: Wisconsin Alumni Research Foundation

Inventor： James Thomson ,  Jue Zhang ,  Igor Slukvin ,  Aditi Majumder ,  Ho Sun Jung

IPC: A61K39/00 ,  A61P35/00 ,  C07K14/725 ,  C07K16/30 ,  C12N5/0783 ,  C12N5/0786 ,  C12N5/0787

CPC classification number: A61K39/464471 ,  A61K39/461 ,  A61K39/4613 ,  A61K39/4614 ,  A61K39/4631 ,  A61P35/00 ,  C07K14/7051 ,  C07K16/3084 ,  C12N5/0642 ,  C12N5/0645 ,  C12N5/0646 ,  C12N2506/45 ,  C12N2510/00

Abstract: This disclosure provides genetically engineered immune cells that express an anti-GD2 chimeric antigen receptor, methods of generating these cells, and methods of treating tumors using the genetically engineered cells.

公开(公告)号：US20130217752A1

公开(公告)日：2013-08-22

申请号：US13772802

申请日：2013-02-21

Applicant: WISCONSIN ALUMNI RESEARCH FOUNDATION

Inventor： Srikumar Sengupta ,  James Thomson

IPC: C12N5/071

CPC classification number: C12N15/113 ,  A61K35/407 ,  A61K35/545 ,  A61K38/38 ,  A61K38/44 ,  A61K38/45 ,  A61K38/57 ,  C12N5/067 ,  C12N5/0672 ,  C12N15/111 ,  C12N2310/141 ,  C12N2320/30 ,  C12N2501/65 ,  C12N2510/00 ,  C12Y114/13017 ,  C12Y114/14001 ,  C12Y206/01005 ,  G01N33/5014

Abstract: A method for producing mature hepatocytes having functional hepatic enzyme activity from human pluripotent cells is disclosed. The method includes the step of transferring an external vector comprising the DNA sequence coding for a microRNA having the seed sequence of the microRNA miR-122, the DNA sequence coding for a microRNA having the seed sequence of the microRNA miR-let-7c, a microRNA having the seed sequence of the microRNA miR-122, a microRNA having the seed sequence of the microRNA miR-let-7c, or a combination thereof into one or more fetal hepatocytes. The resulting cells differentiate into mature hepatocytes that exhibit functional hepatic enzyme activity, and can be used in drug metabolism and toxicity testing, in the study of viruses that target hepatic tissue, and as therapeutics.A related method of maintaining the functional hepatic enzyme activity of primary hepatocytes over time is also disclosed. The method includes the step of transferring an external vector comprising the DNA sequence coding for a microRNA having the seed sequence of the microRNA miR-122 into one or more cultured primary hepatocytes.

Abstract translation: 公开了一种从人多能细胞产生具有功能性肝酶活性的成熟肝细胞的方法。 该方法包括转移包含编码具有微小RNA miR-122的种子序列的微小RNA的DNA序列的外部载体的步骤，编码具有微小RNA miR-let-7c的种子序列的微小RNA的DNA序列， 具有微RNA miR-122的种子序列的微小RNA，具有微小RNA miR-let-7c的种子序列的微RNA或其组合成一个或多个胎儿肝细胞。 所得细胞分化成成熟的肝细胞，其表现出功能性肝酶活性，并且可用于药物代谢和毒性测试，用于靶向肝组织的病毒的研究以及作为治疗剂。 还公开了维持原代肝细胞功能性肝酶活性的相关方法。 该方法包括将包含编码具有微小RNA miR-122的种子序列的微小RNA的DNA序列的外部载体转移到一个或多个培养的原代肝细胞中的步骤。

公开(公告)号：US20240067982A1

公开(公告)日：2024-02-29

申请号：US18058419

申请日：2022-11-23

Applicant: Northwestern University ,  Wisconsin Alumni Research Foundation

Inventor： Erik J. Sontheimer ,  Yan Zhang ,  Alfonzo Mondragon ,  Rakhi Rajan ,  James Thomson ,  Zhonggang Hou

IPC: C12N15/85 ,  C07K14/22 ,  C12N9/22 ,  C12N15/63 ,  C12N15/90

CPC classification number: C12N15/85 ,  C07K14/22 ,  C12N9/22 ,  C12N15/63 ,  C12N15/907 ,  C07K2319/20

Abstract: Disclosed are components and methods for RNA-directed DNA cleavage and gene editing. The components include and the methods utilize a Cas9 protein from Neisseria and one or more RNA molecules in order to direct the Cas9 protein to bind to and optionally cleave or nick a target sequence.