公开(公告)号：US20210324035A1

公开(公告)日：2021-10-21

申请号：US17273192

申请日：2019-09-04

申请人： The Regents of the University of California ,  California Institute of Technology ,  The Olivia Newton-John Cancer Research Institute

发明人： Owen N. Witte ,  Jami McLaughlin Witte ,  Antoni Ribas ,  Lili Yang ,  Michael T. Bethune ,  Jonathan Cebon ,  Katherine Woods ,  Ashley J. Knights ,  David Baltimore

IPC分类号： C07K14/725 ,  A61K35/17 ,  C12N15/86 ,  C12N5/0783 ,  A61P35/00

摘要： Tumor-specific T cell receptor (TCR) gene transfer enables specific and potent immune targeting of tumor antigens. The canonical cancer-testis antigen, NY-ESO-1, is not expressed in normal tissues but is aberrantly expressed across a broad array of cancer types. It has also been targeted with A2-restricted TCR gene therapy without adverse events or notable side effects. To enable the targeting of NY-ESO-1 in a broader array of HLA haplotypes, we isolated TCRs specific for NY-ESO-1 epitopes presented by four MHC molecules: HLA-A2, -B07, -B18, and -C03. Using these TCRs, we have developed an approach to extend TCR gene therapies targeting NY-ESO-1 to patient populations beyond those expressing HLA-A2.

公开(公告)号：US20170107519A1

公开(公告)日：2017-04-20

申请号：US15395348

申请日：2016-12-30

申请人： California Institute of Technology ,  The Regents of the University of California

发明人： Carlos Lois-Caballe ,  David Baltimore ,  Xiao-Feng Qin ,  Irvin S.Y. Chen ,  Dong Sung An

IPC分类号： C12N15/113 ,  C12N15/11 ,  C12N15/86

CPC分类号： C12N15/1132 ,  A61K48/00 ,  C12N15/111 ,  C12N15/113 ,  C12N15/1138 ,  C12N15/63 ,  C12N15/86 ,  C12N2310/111 ,  C12N2310/14 ,  C12N2330/30 ,  C12N2740/16043 ,  C12N2740/16045 ,  C12N2760/20122 ,  C12N2799/027 ,  C12N2810/609 ,  C12N2830/003 ,  C12N2830/008 ,  C12N2830/48 ,  C12N2840/203

摘要： In one aspect, the invention provides methods and compositions for the expression of small RNA molecules within a cell using a retroviral vector (FIG. 1A). Small interfering RNA (siRNA) can be expressed using the methods of the invention within a cell. In a further aspect, the invention provides methods for producing siRNA encoding lentivirus where the siRNA activity may interfere with the lentiviral life cycle. In yet a further aspect, the invention provides methods for expression of a small RNA molecule within a cell, such as an siRNA capable of downregulating CCR5, wherein expression of the small RNA molecule is relatively non-cytotoxic to the cell. The invention also includes small RNA molecules, such as an siRNA capable of downregulating CCR5, that are relatively non-cytotoxic to cells.

公开(公告)号：US09567592B2

公开(公告)日：2017-02-14

申请号：US14695462

申请日：2015-04-24

申请人： CALIFORNIA INSTITUTE OF TECHNOLOGY ,  The Regents of the University of California

发明人： Carlos Lois-Caballe ,  David Baltimore ,  Xiao-Feng Qin ,  Irvin S. Y. Chen ,  Dong Sung An

IPC分类号： C12N15/113 ,  C12N15/867 ,  A61P31/18 ,  C12N15/63 ,  C12N15/11 ,  C12N15/86 ,  A61K48/00

CPC分类号： C12N15/1132 ,  A61K48/00 ,  C12N15/111 ,  C12N15/113 ,  C12N15/1138 ,  C12N15/63 ,  C12N15/86 ,  C12N2310/111 ,  C12N2310/14 ,  C12N2330/30 ,  C12N2740/16043 ,  C12N2740/16045 ,  C12N2760/20122 ,  C12N2799/027 ,  C12N2810/609 ,  C12N2830/003 ,  C12N2830/008 ,  C12N2830/48 ,  C12N2840/203

摘要： In one aspect, the invention provides methods and compositions for the expression of small RNA molecules within a cell using a retroviral vector (FIG. 1A). Small interfering RNA (siRNA) can be expressed using the methods of the invention within a cell. In a further aspect, the invention provides methods for producing siRNA encoding lentivirus where the siRNA activity may interfere with the lentiviral life cycle. In yet a further aspect, the invention provides methods for expression of a small RNA molecule within a cell, such as an siRNA capable of downregulating CCR5, wherein expression of the small RNA molecule is relatively non-cytotoxic to the cell. The invention also includes small RNA molecules, such as an siRNA capable of downregulating CCR5, that are relatively non-cytotoxic to cells.

摘要翻译： 一方面，本发明提供了使用逆转录病毒载体在细胞内表达小RNA分子的方法和组合物（图1A）。 可以使用本发明的方法在细胞内表达小干扰RNA（siRNA）。 另一方面，本发明提供了用于产生编码慢病毒的siRNA的方法，其中siRNA活性可能干扰慢病毒生命周期。 在另一方面，本发明提供了在细胞内表达小RNA分子的方法，例如能够下调CCR5的siRNA，其中小RNA分子的表达对细胞是相对非细胞毒性的。 本发明还包括对细胞相对非细胞毒性的小RNA分子，例如能够下调CCR5的siRNA。

公开(公告)号：US20130295615A1

公开(公告)日：2013-11-07

申请号：US13749319

申请日：2013-01-24

申请人： The Regents of the University of California ,  California Institute of Technology

发明人： Carlos Lois-Caballe ,  David Baltimore ,  Xiao-Feng Qin ,  Irvin S.Y. Chen ,  Dong Sung An

IPC分类号： C12N15/113

CPC分类号： C12N15/1132 ,  A61K48/00 ,  C12N15/111 ,  C12N15/113 ,  C12N15/1138 ,  C12N15/63 ,  C12N15/86 ,  C12N2310/111 ,  C12N2310/14 ,  C12N2330/30 ,  C12N2740/16043 ,  C12N2740/16045 ,  C12N2760/20122 ,  C12N2799/027 ,  C12N2810/609 ,  C12N2830/003 ,  C12N2830/008 ,  C12N2830/48 ,  C12N2840/203

摘要： In one aspect, the invention provides methods and compositions for the expression of small RNA molecules within a cell using a retroviral vector (FIG. 1A). Small interfering RNA (siRNA) can be expressed using the methods of the invention within a cell. In a further aspect, the invention provides methods for producing siRNA encoding lentivirus where the siRNA activity may interfere with the lentiviral life cycle. In yet a further aspect, the invention provides methods for expression of a small RNA molecule within a cell, such as an siRNA capable of downregulating CCR5, wherein expression of the small RNA molecule is relatively non-cytotoxic to the cell. The invention also includes small RNA molecules, such as an siRNA capable of downregulating CCR5, that are relatively non-cytotoxic to cells.

公开(公告)号：US20190002883A1

公开(公告)日：2019-01-03

申请号：US16028262

申请日：2018-07-05

申请人： California Institute of Technology ,  The Regents of the University of California

发明人： Carlos Lois-Caballe ,  David Baltimore ,  Xiao-Feng Qin ,  Irvin S.Y. Chen ,  Dong Sung An

IPC分类号： C12N15/113 ,  C12N15/11 ,  C12N15/63 ,  C12N15/86 ,  A61K48/00

摘要： In one aspect, the invention provides methods and compositions for the expression of small RNA molecules within a cell using a retroviral vector (FIG. 1A). Small interfering RNA (siRNA) can be expressed using the methods of the invention within a cell. In a further aspect, the invention provides methods for producing siRNA encoding lentivirus where the siRNA activity may interfere with the lentiviral life cycle. In yet a further aspect, the invention provides methods for expression of a small RNA molecule within a cell, such as an siRNA capable of downregulating CCR5, wherein expression of the small RNA molecule is relatively non-cytotoxic to the cell. The invention also includes small RNA molecules, such as an siRNA capable of downregulating CCR5, that are relatively non-cytotoxic to cells.

公开(公告)号：US20150218564A1

公开(公告)日：2015-08-06

申请号：US14695462

申请日：2015-04-24

申请人： CALIFORNIA INSTITUTE OF TECHNOLOGY ,  The Regents of the University of California

发明人： Carlos Lois-Caballe ,  David Baltimore ,  Xiao-Feng Qin ,  Irvin S.Y. Chen ,  Dong Sung An

IPC分类号： C12N15/63

CPC分类号： C12N15/1132 ,  A61K48/00 ,  C12N15/111 ,  C12N15/113 ,  C12N15/1138 ,  C12N15/63 ,  C12N15/86 ,  C12N2310/111 ,  C12N2310/14 ,  C12N2330/30 ,  C12N2740/16043 ,  C12N2740/16045 ,  C12N2760/20122 ,  C12N2799/027 ,  C12N2810/609 ,  C12N2830/003 ,  C12N2830/008 ,  C12N2830/48 ,  C12N2840/203

摘要： In one aspect, the invention provides methods and compositions for the expression of small RNA molecules within a cell using a retroviral vector (FIG. 1A). Small interfering RNA (siRNA) can be expressed using the methods of the invention within a cell. In a further aspect, the invention provides methods for producing siRNA encoding lentivirus where the siRNA activity may interfere with the lentiviral life cycle. In yet a further aspect, the invention provides methods for expression of a small RNA molecule within a cell, such as an siRNA capable of downregulating CCR5, wherein expression of the small RNA molecule is relatively non-cytotoxic to the cell. The invention also includes small RNA molecules, such as an siRNA capable of downregulating CCR5, that are relatively non-cytotoxic to cells.

摘要翻译： 一方面，本发明提供了使用逆转录病毒载体在细胞内表达小RNA分子的方法和组合物（图1A）。 可以使用本发明的方法在细胞内表达小干扰RNA（siRNA）。 另一方面，本发明提供了用于产生编码慢病毒的siRNA的方法，其中siRNA活性可能干扰慢病毒生命周期。 在另一方面，本发明提供了在细胞内表达小RNA分子的方法，例如能够下调CCR5的siRNA，其中小RNA分子的表达对细胞是相对非细胞毒性的。 本发明还包括对细胞相对非细胞毒性的小RNA分子，例如能够下调CCR5的siRNA。

公开(公告)号：US09862948B2

公开(公告)日：2018-01-09

申请号：US15016096

申请日：2016-02-04

申请人： California Institute of Technology

发明人： David Baltimore ,  Ryan M. O'Connell ,  Konstantin Taganov ,  Mark Boldin

IPC分类号： A01N43/04 ,  C12Q1/68 ,  C12N15/113 ,  A61K31/56 ,  A61K45/06 ,  A61K31/7105

CPC分类号： C12N15/113 ,  A61K31/56 ,  A61K31/7105 ,  A61K45/06 ,  C12N2310/11 ,  C12N2310/113 ,  C12N2310/141 ,  C12N2320/31

摘要： The present disclosure relates to the finding that microRNA-155 plays a role in inflammation, hematopoiesis and myeloproliferation, and that dysregulation of microRNA-155 expression is associated with particular myeloproliferative disorders. Disclosed herein are methods and compositions for diagnosing an treating disorders, including inflammation and myeloproliferation, modulating the levels of expression of one or more genes selected from the group consisting of Cutl1, Arnt1, Picalm, Jarid2, PU.1, Csf1r, HIF1α, Sla, Cebpβ, and Bach1, and the like.

公开(公告)号：US09696296B2

公开(公告)日：2017-07-04

申请号：US14166681

申请日：2014-01-28

申请人： California Institute of Technology

发明人： Parameswaran Ramakrishnan ,  David Baltimore

IPC分类号： A61K31/00 ,  G01N33/50 ,  A61K31/513 ,  A61K31/655 ,  A61K31/7028

CPC分类号： G01N33/5023 ,  A61K31/513 ,  A61K31/655 ,  A61K31/7028 ,  G01N2440/38

摘要： Serine 350 has been identified as the site of O-GlycNAcylation of c-Rel. Methods are provided for identifying compositions capable of blocking c-Rel activation. The methods generally involve identifying compounds that inhibit O-GlcNAcylation of c-Rel at the serine 350 residue, thereby preventing c-Rel activation and production of c-Rel-dependent cytokines.

公开(公告)号：US09551011B2

公开(公告)日：2017-01-24

申请号：US14622064

申请日：2015-02-13

申请人： California Institute of Technology

发明人： Carlos Lois-Caballe ,  David Baltimore ,  Xiao-Feng Qin

IPC分类号： C12N15/867 ,  A61K48/00 ,  C12N15/86 ,  C12N15/113 ,  C12Q1/68 ,  A61K38/00

CPC分类号： C12N15/86 ,  A61K38/00 ,  A61K48/00 ,  C12N7/00 ,  C12N15/113 ,  C12N15/1132 ,  C12N15/1138 ,  C12N15/867 ,  C12N2310/111 ,  C12N2310/14 ,  C12N2310/53 ,  C12N2310/531 ,  C12N2330/30 ,  C12N2740/15043 ,  C12N2740/16043 ,  C12N2830/003 ,  C12N2830/006 ,  C12N2830/008 ,  C12N2830/30 ,  C12N2830/48 ,  C12N2830/60 ,  C12N2830/85 ,  C12N2840/20 ,  C12N2840/203 ,  C12Q1/6897 ,  Y02A50/465

摘要： The invention provides methods and compositions for the expression of small RNA molecules within a cell using a lentiviral vector. The methods can be used to express doubles stranded RNA complexes. Small interfering RNA (siRNA) can be expressed using the methods of the invention within a cell, which are capable of down regulating the expression of a target gene through RNA interference. A variety of cells can be treated according to the methods of the invention including embryos, embryogenic stem cells, allowing for the generation of transgenic animals or animals constituted partly by the transduced cells that have a specific gene or a group of genes down regulated.

摘要翻译： 本发明提供了使用慢病毒载体在细胞内表达小RNA分子的方法和组合物。 该方法可用于表达双链RNA复合物。 可以使用本发明的方法在细胞内表达小干扰RNA（siRNA），其能够通过RNA干扰下调靶基因的表达。 可以根据本发明的方法处理各种细胞，包括胚胎，胚胎干细胞，允许产生部分由转导细胞组成的转基因动物或动物，所述转导细胞具有特定基因或一组基因下调。

公开(公告)号：US09527904B2

公开(公告)日：2016-12-27

申请号：US14484842

申请日：2014-09-12

申请人： California Institute of Technology

发明人： Alejandro Benjamin Balazs ,  David Baltimore

IPC分类号： A61K48/00 ,  C07H21/04 ,  C07K16/10 ,  C12N7/00 ,  A01K67/00

CPC分类号： C07K16/109 ,  C07K16/1045 ,  C12N7/00 ,  C12N2750/14141 ,  C12N2750/14143

摘要： Disclosed herein are compositions, systems and methods for delivery of proteins of interest using adeno-associated virus (AAV) vectors.

摘要翻译： 本文公开了使用腺相关病毒（AAV）载体递送感兴趣的蛋白质的组合物，系统和方法。