公开(公告)号：US20190321490A1

公开(公告)日：2019-10-24

申请号：US16225489

申请日：2018-12-19

申请人： CELLSCRIPT, LLC

发明人： Judith Meis ,  Anthony Person ,  Cynthia Chin ,  Jerome Jendrisak ,  Gary Dahl

IPC分类号： A61K48/00 ,  C12P19/34 ,  C12N5/074 ,  C12N15/10 ,  C12N5/0793 ,  A61K33/06 ,  C12P21/02 ,  A61K38/00 ,  C12P19/38 ,  C12N15/87 ,  A61K31/7105 ,  C12N5/077

摘要： The present invention relates to compositions, kits and methods for making and using RNA compositions comprising in vitro-synthesized ssRNA inducing a biological or biochemical effect in a mammalian cell or organism into which the RNA composition is repeatedly or continuously introduced. In certain embodiments, the invention provides compositions and methods for changing the state of differentiation or phenotype of a human or other vertebrate cell. For example, the present invention provides mRNA and methods for reprogramming cells that exhibit a first differentiated state or phenotype to cells that exhibit a second differentiated state or phenotype, such as to reprogram human somatic cells to pluripotent stem cells.

公开(公告)号：US20180312806A1

公开(公告)日：2018-11-01

申请号：US15823869

申请日：2017-11-28

申请人： CellScript, LLC

发明人： Cynthia Chin ,  Anthony D. Person ,  Gary A. Dahl

IPC分类号： C12N5/078 ,  A61K38/16 ,  C07K14/005 ,  C12N5/074 ,  C12N5/077 ,  A61K31/711 ,  A61K38/21 ,  A61K38/17 ,  C07K14/705 ,  A61K31/7105 ,  C07K14/715

CPC分类号： C12N5/0634 ,  A61K31/7105 ,  A61K31/711 ,  A61K38/162 ,  A61K38/1774 ,  A61K38/21 ,  C07K14/005 ,  C07K14/70503 ,  C07K14/7156 ,  C12N5/0658 ,  C12N5/0696 ,  C12N2710/20022 ,  C12N2710/22022 ,  C12N2710/24122 ,  C12N2760/16122 ,  A61K2300/00

摘要： The present invention provides methods, kits, and compositions for reducing an innate immune system response in a human or animal cell, tissue or organism. One embodiment comprises: introducing an Agent mRNA comprising in vitro-synthesized mRNA encoding one or more proteins that affect the induction, activity or response of an innate immune response pathway; whereby, the innate immune response in the cell, tissue or organism is reduced compared to the innate immune response in the absence of the Agent mRNA. Other embodiments are methods, compositions and kits for using an Agent mRNA for treating a disease or medical condition in a human or animal that exhibits symptoms of an elevated innate immune system, or for reducing an innate immune response that is induced in a human or animal cell, tissue or organism by a Foreign Substance that is administered to the cell, tissue or organism.

公开(公告)号：US11135314B2

公开(公告)日：2021-10-05

申请号：US16225489

申请日：2018-12-19

申请人： CELLSCRIPT, LLC

发明人： Judith Meis ,  Anthony Person ,  Cynthia Chin ,  Jerome Jendrisak ,  Gary Dahl

IPC分类号： A61K48/00 ,  A61K38/00 ,  A61K31/7105 ,  A61K33/06 ,  C12N15/10 ,  C12P21/02 ,  C12P19/34 ,  C12N5/074 ,  C12N5/0793 ,  C12N5/077 ,  C12N15/87 ,  C12P19/38

摘要： The present invention relates to compositions, kits and methods for making and using RNA compositions comprising in vitro-synthesized ssRNA inducing a biological or biochemical effect in a mammalian cell or organism into which the RNA composition is repeatedly or continuously introduced. In certain embodiments, the invention provides compositions and methods for changing the state of differentiation or phenotype of a human or other vertebrate cell. For example, the present invention provides mRNA and methods for reprogramming cells that exhibit a first differentiated state or phenotype to cells that exhibit a second differentiated state or phenotype, such as to reprogram human somatic cells to pluripotent stem cells.

公开(公告)号：US20210000926A1

公开(公告)日：2021-01-07

申请号：US16968792

申请日：2019-02-19

申请人： The United States of America, as represented by the Secretary, Department of Health and Human Servic ,  CELLSCRIPT, LLC

发明人： Suk See De Ravin ,  Harry L. Malech ,  Ron Meis ,  Gary A. Dahl

IPC分类号： A61K38/44 ,  A61K35/17 ,  A61K35/15 ,  C12N9/02 ,  C12N5/0787 ,  C12N5/0783 ,  A61P31/00 ,  A61K35/28 ,  A61K45/06

摘要： Provided are compositions and methods for treating a subject having a primary immune deficiency (PID), for example who is suffering from a chronic viral, bacterial, or fungal infection, using autologous granulocytes, autologous lymphocytes, and/or NK cells containing exogenous mRNA encoding the missing or defective protein.

公开(公告)号：US20140363876A1

公开(公告)日：2014-12-11

申请号：US14471649

申请日：2014-08-28

申请人： CELLSCRIPT, LLC

发明人： Jerome Jendrisak ,  Ronald Meis ,  Gary Dahl

IPC分类号： C12P19/34

CPC分类号： C12P19/34 ,  C12N9/1007 ,  C12N9/1241 ,  C12N15/1072 ,  C12N15/1075 ,  C12N15/1096 ,  C12N15/111 ,  C12N15/113 ,  C12N2310/317 ,  C12N2320/51 ,  C12Y201/01056 ,  C12Y201/01057 ,  C12Y207/07019 ,  C12Y207/0705

摘要： The present invention relates to kits and methods for efficiently generating 5′ capped RNA having a modified cap nucleotide and for use of such modified-nucleotide-capped RNA molecules. In particular, the present invention provides kits and methods for capping RNA using a modified cap nucleotide and a capping enzyme system, such as poxvirus capping enzyme. The present invention finds use for in vitro production of 5′-capped RNA having a modified cap nucleotide and for in vitro or in vivo production of polypeptides by in vitro or in vivo translation of such modified-nucleotide-capped RNA. The invention also provides methods and kits for capturing or isolating uncapped RNA comprising primary RNA transcripts or RNA having a 5′-diphosphate, and methods and kits for using a capping enzyme system and modified cap nucleotides for labeling uncapped RNA comprising primary RNA transcripts or RNA having a 5′-diphosphate with detectable dye or enzyme moieties.

公开(公告)号：US20140328825A1

公开(公告)日：2014-11-06

申请号：US14368399

申请日：2012-12-31

申请人： CELLSCRIPT, LLC

发明人： Judith Meis ,  Anthony Person ,  Cynthia Chin ,  Jerome Jendrisak ,  Gary Dahl

IPC分类号： A61K48/00 ,  C12N5/0793 ,  C12N5/077 ,  C12N15/87 ,  C12P19/38

CPC分类号： A61K48/0066 ,  A61K31/7105 ,  A61K33/06 ,  A61K38/005 ,  A61K48/0041 ,  C12N5/0619 ,  C12N5/0658 ,  C12N5/0696 ,  C12N15/1003 ,  C12N15/1096 ,  C12N15/87 ,  C12N2501/60 ,  C12N2501/602 ,  C12N2501/603 ,  C12N2501/604 ,  C12N2501/605 ,  C12N2501/606 ,  C12N2501/608 ,  C12N2501/73 ,  C12N2506/1307 ,  C12N2510/00 ,  C12P19/34 ,  C12P19/38 ,  C12P21/02 ,  C12Y301/26003 ,  A61K2300/00

摘要： The present invention relates to compositions, kits and methods for making and using RNA compositions comprising in vitro-synthesized ssRNA inducing a biological or biochemical effect in a mammalian cell or organism into which the RNA composition is repeatedly or continuously introduced. In certain embodiments, the invention provides compositions and methods for changing the state of differentiation or phenotype of a human or other vertebrate cell. For example, the present invention provides mRNA and methods for reprogramming cells that exhibit a first differentiated state or phenotype to cells that exhibit a second differentiated state or phenotype, such as to reprogram human somatic cells to pluripotent stem cells.

摘要翻译： 本发明涉及用于制备和使用RNA组合物的组合物，试剂盒和方法，所述RNA组合物包含在哺乳动物细胞或生物体中诱导生物或生物化学作用的体外合成的ssRNA，RNA组合物重复或连续引入。 在某些实施方案中，本发明提供用于改变人或其他脊椎动物细胞的分化或表型状态的组合物和方法。 例如，本发明提供了mRNA和方法，用于对表现出第二分化状态或表型的细胞（例如将人体细胞重编程为多能干细胞）展现出第一分化状态或表型的细胞重编程。

公开(公告)号：US20140315988A1

公开(公告)日：2014-10-23

申请号：US14322526

申请日：2014-07-02

申请人： CELLSCRIPT, LLC

发明人： Gary Dahl ,  Anthony Person ,  Judith Meis ,  Jerome Jendrisak

IPC分类号： C12N15/85

CPC分类号： C12N5/0696 ,  A61K38/1709 ,  A61K38/1816 ,  A61K38/44 ,  A61K38/465 ,  A61K38/50 ,  A61K48/005 ,  A61K48/0075 ,  C07K14/47 ,  C07K14/4712 ,  C07K14/505 ,  C12N9/0075 ,  C12N9/22 ,  C12N9/78 ,  C12N15/117 ,  C12N15/85 ,  C12N15/87 ,  C12N2310/17 ,  C12N2310/335 ,  C12N2320/30 ,  C12N2501/602 ,  C12N2501/603 ,  C12N2501/604 ,  C12N2501/605 ,  C12N2501/606 ,  C12N2501/608 ,  C12N2506/02 ,  C12Y114/13039 ,  C12Y301/04012 ,  C12Y305/04004

摘要： The present invention relates to methods for changing the state of differentiation of a eukaryotic cell, the methods comprising introducing mRNA encoding one or more reprogramming factors into a cell and maintaining the cell under conditions wherein the cell is viable and the mRNA that is introduced into the cell is expressed in sufficient amount and for sufficient time to generate a cell that exhibits a changed state of differentiation compared to the cell into which the mRNA was introduced, and compositions therefor. For example, the present invention provides mRNA molecules and methods for their use to reprogram human somatic cells into pluripotent stem cells.

摘要翻译： 本发明涉及用于改变真核细胞分化状态的方法，所述方法包括将编码一种或多种重编程因子的mRNA引入细胞并将细胞维持在其中细胞存活的条件下，并将导入 表达足够量的细胞并足够的时间产生与引入mRNA的细胞相比表现出改变的分化状态的细胞及其组合物。 例如，本发明提供mRNA分子及其用于将人体细胞重编程为多能干细胞的方法。

公开(公告)号：US20240181005A1

公开(公告)日：2024-06-06

申请号：US17998752

申请日：2021-05-17

申请人： CellScript, LLC ,  THE UNITED STATES OF AMERICA, AS REPRESENTED BY THE SECRETARY, DEPARTMENT OF HEALTH AND HUMAN SERVIC

发明人： Ronald Meis ,  Gary Dahl ,  Suk See De Ravin ,  Julie Brault ,  Colin L. Sweeney ,  Harry L. Malech

IPC分类号： A61K38/17 ,  A61K31/4184 ,  A61K31/428 ,  A61K31/44 ,  A61K31/7105 ,  A61K35/17 ,  A61K35/28 ,  A61K35/545 ,  A61K38/46 ,  A61K48/00 ,  A61P37/04 ,  C12N9/22 ,  C12N15/11 ,  C12N15/86 ,  C12N15/90

CPC分类号： A61K38/177 ,  A61K31/4184 ,  A61K31/428 ,  A61K31/44 ,  A61K31/7105 ,  A61K35/17 ,  A61K35/28 ,  A61K35/545 ,  A61K38/465 ,  A61K48/0033 ,  A61P37/04 ,  C12N9/22 ,  C12N15/11 ,  C12N15/86 ,  C12N15/907 ,  C12N2310/20 ,  C12N2750/14143 ,  C12N2800/80

摘要： The present invention relates to compositions, systems, and methods for editing a disease/condition causing mutation region in a target gene in a cell. In certain embodiments, the following components are employed: i) mRNA encoding a Tumor Protein p53 (TP53) inhibitor, ii) an inhibiting agent that inhibits Tumor Suppressor p53-Binding Protein 1 (53BPI) (e.g., small molecule EoHR or mRNA encoding a protein that inhibits 53BPI), iii) mRNA encoding a Cas nuclease for CRISPR; iv) a guide RNA specific for a target cleavage site proximal to said disease/condition-causing mutation region; and v) a repair template comprising a region of interest configured to replace said disease/condition-causing mutation region in the target gene during homology-directed repair (HDR). In certain embodiments, the cell is a T-cell, stem cell (e.g., hematopoietic stem cell), or progenitor cell from a subject with the disease or condition (e.g., a Primary Immunodeficiency Disease (PID)). In some embodiments, the gene-edited cell is administered to the subject.

公开(公告)号：US09005930B2

公开(公告)日：2015-04-14

申请号：US14471649

申请日：2014-08-28

申请人： Cellscript, LLC

发明人： Jerome Jendrisak ,  Ronald Meis ,  Gary Dahl

IPC分类号： C12P19/34 ,  C12P21/06

CPC分类号： C12P19/34 ,  C12N9/1007 ,  C12N9/1241 ,  C12N15/1072 ,  C12N15/1075 ,  C12N15/1096 ,  C12N15/111 ,  C12N15/113 ,  C12N2310/317 ,  C12N2320/51 ,  C12Y201/01056 ,  C12Y201/01057 ,  C12Y207/07019 ,  C12Y207/0705

摘要： The present invention relates to kits and methods for efficiently generating 5′ capped RNA having a modified cap nucleotide and for use of such modified-nucleotide-capped RNA molecules. In particular, the present invention provides kits and methods for capping RNA using a modified cap nucleotide and a capping enzyme system, such as poxvirus capping enzyme. The present invention finds use for in vitro production of 5′-capped RNA having a modified cap nucleotide and for in vitro or in vivo production of polypeptides by in vitro or in vivo translation of such modified-nucleotide-capped RNA. The invention also provides methods and kits for capturing or isolating uncapped RNA comprising primary RNA transcripts or RNA having a 5′-diphosphate, and methods and kits for using a capping enzyme system and modified cap nucleotides for labeling uncapped RNA comprising primary RNA transcripts or RNA having a 5′-diphosphate with detectable dye or enzyme moieties.

公开(公告)号：US20140221248A1

公开(公告)日：2014-08-07

申请号：US14185384

申请日：2014-02-20

申请人： CELLSCRIPT, LLC

发明人： Jerome Jendrisak ,  Ronald Meis ,  Gary Dahl

IPC分类号： C12N15/10

CPC分类号： C12P19/34 ,  C12N9/1007 ,  C12N9/1241 ,  C12N15/1072 ,  C12N15/1075 ,  C12N15/1096 ,  C12N15/111 ,  C12N15/113 ,  C12N2310/317 ,  C12N2320/51 ,  C12Y201/01056 ,  C12Y201/01057 ,  C12Y207/07019 ,  C12Y207/0705

摘要： The present invention relates to kits and methods for efficiently generating 5′ capped RNA having a modified cap nucleotide and for use of such modified-nucleotide-capped RNA molecules. In particular, the present invention provides kits and methods for capping RNA using a modified cap nucleotide and a capping enzyme system, such as poxvirus capping enzyme. The present invention finds use for in vitro production of 5′-capped RNA having a modified cap nucleotide and for in vitro or in vivo production of polypeptides by in vitro or in vivo translation of such modified-nucleotide-capped RNA. The invention also provides methods and kits for capturing or isolating uncapped RNA comprising primary RNA transcripts or RNA having a 5′-diphosphate, and methods and kits for using a capping enzyme system and modified cap nucleotides for labeling uncapped RNA comprising primary RNA transcripts or RNA having a 5′-diphosphate with detectable dye or enzyme moieties.

摘要翻译： 本发明涉及用于有效产生具有修饰的帽核苷酸的5'封端RNA并用于这种经修饰的核苷酸封端的RNA分子的试剂盒和方法。 特别地，本发明提供了使用修饰的帽核苷酸和封端酶系统（例如痘病毒覆盖酶）对RNA进行封端的试剂盒和方法。 本发明用于通过体外或体内翻译这些经修饰的核苷酸加帽的RNA来体外生产具有修饰的帽核苷酸的5'-加帽的RNA，以及体外或体内产生多肽。 本发明还提供用于捕获或分离包含初级RNA转录物或具有5'-二磷酸的RNA的未封端RNA的方法和试剂盒，以及使用封端酶系统和修饰的帽核苷酸用于标记包含初级RNA转录物或RNA的未加帽RNA的方法和试剂盒 具有可检测的染料或酶部分的5'-二磷酸酯。