公开(公告)号：US20170114365A1

公开(公告)日：2017-04-27

申请号：US15391189

申请日：2016-12-27

Applicant: California Institute of Technology

Inventor： Carlos Lois-Caballe ,  David Baltimore ,  Xiao-Feng Qin

IPC: C12N15/86 ,  C12N15/113 ,  C12N7/00

CPC classification number: 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

Abstract: 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 is 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.

公开(公告)号：US09540657B2

公开(公告)日：2017-01-10

申请号：US13901940

申请日：2013-05-24

Applicant: California Institute of Technology

Inventor： Kenneth Yu ,  David Baltimore ,  Lili Yang

IPC: C12N15/85 ,  C12N15/86 ,  C12N15/90 ,  G01N33/58 ,  G01N33/68

CPC classification number: C12N15/85 ,  C07K2319/00 ,  C12N15/86 ,  C12N15/907 ,  C12N2740/15043 ,  G01N33/582 ,  G01N33/68

Abstract: Some embodiments herein provide compositions and methods for expressing secreted and cell-surface-bound polypeptides in a single cell. In some embodiments, secreted and cell-surface polypeptide are produced from a single polynucleotide. The polynucleotide can comprise a sequence (or sequence encoding a polypeptide) that mediates separation of a membrane anchor from the polypeptide. In some embodiments, a desired ratio of secreted to surface-bound polypeptide is obtained by selecting a sequence that mediates a desired level of separation of the membrane anchor from the polypeptide.

Abstract translation: 本文的一些实施方案提供了用于在单个细胞中表达分泌的和细胞表面结合的多肽的组合物和方法。 在一些实施方案中，分泌的和细胞表面多肽由单个多核苷酸产生。 多核苷酸可以包含介导膜锚定体与多肽分离的序列（或编码多肽的序列）。 在一些实施方案中，分泌到表面结合多肽的期望比例通过选择介导膜锚与多肽分离的期望水平的序列来获得。

公开(公告)号：US20160222409A1

公开(公告)日：2016-08-04

申请号：US14338947

申请日：2014-07-23

Applicant: CALIFORNIA INSTITUTE OF TECHNOLOGY

Inventor： David Baltimore ,  Pin Wang ,  Lili Yang

IPC: C12N15/86

CPC classification number: C12N15/86 ,  A61K2039/505 ,  C07K16/2887 ,  C07K2317/53 ,  C07K2317/622 ,  C07K2319/00 ,  C07K2319/03 ,  C12N2740/15043 ,  C12N2740/16043 ,  C12N2740/16045 ,  C12N2799/027 ,  C12N2810/80 ,  C12N2810/851 ,  C12N2810/859 ,  Y02A50/386 ,  Y02A50/396

Abstract: Methods and compositions are provided for delivering a polynucleotide encoding a gene of interest to a target cell using a virus. The virus envelope comprises a cell-specific binding determinant that recognizes and binds to a component on the target cell surface, leading to endocytosis of the virus. A separate fusogenic molecule is also present on the envelope and facilitates delivery of the polynucleotide across the membrane and into the cytosol of the target cell. The methods and related compositions can be used for treating patients having suffering from a wide range of conditions, including infection, such as HIV; cancers, such as non-Hodgkin's lymphoma and breast cancer; and hematological disorders, such as severe combined immunodeficiency.

Abstract translation: 提供了使用病毒将编码目标基因的多核苷酸递送至靶细胞的方法和组合物。 病毒包膜包含识别和结合靶细胞表面上的组分的细胞特异性结合决定簇，导致病毒的内吞。 单独的融合分子也存在于包膜上并促进多核苷酸穿过膜并进入靶细胞的胞质溶胶。 方法和相关组合物可用于治疗患有广泛病症（包括HIV感染）的患者; 癌症，如非霍奇金淋巴瘤和乳腺癌; 和血液学疾病，如严重的联合免疫缺陷。

公开(公告)号：US20150152435A1

公开(公告)日：2015-06-04

申请号：US14622064

申请日：2015-02-13

Applicant: California Institute of Technology

Inventor： Carlos Lois-Caballe ,  David Baltimore ,  Xiao-Feng Qin

IPC: C12N15/86 ,  C12N15/113

CPC classification number: 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

Abstract: 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.

Abstract translation: 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：US09034577B2

公开(公告)日：2015-05-19

申请号：US13749319

申请日：2013-01-24

Applicant: California Institute of Technology

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

IPC: C12N15/86 ,  C12N15/867 ,  C07H21/02 ,  C12N15/11 ,  C12N15/113 ,  A61K48/00

CPC classification number: 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

Abstract: 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.

Abstract translation: 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：US08969076B2

公开(公告)日：2015-03-03

申请号：US13750903

申请日：2013-01-25

Applicant: California Institute of Technology

Inventor： Carlos Lois-Caballe ,  David Baltimore ,  Xiao-Feng Qin

IPC: C12N15/113 ,  C12N15/867 ,  A61K48/00

CPC classification number: 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

Abstract: 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.

公开(公告)号：US08906359B2

公开(公告)日：2014-12-09

申请号：US13887908

申请日：2013-05-06

Applicant: California Institute of Technology

Inventor： Pin Wang ,  Lili Yang ,  David Baltimore

IPC: A01N63/00 ,  A01N65/00 ,  A61K48/00 ,  C12N5/00

CPC classification number: C12N15/86 ,  A61K31/70 ,  A61K35/76 ,  A61K38/177 ,  A61K38/1774 ,  A61K38/178 ,  A61K38/1793 ,  A61K38/191 ,  A61K38/193 ,  A61K38/20 ,  A61K38/2013 ,  A61K38/2026 ,  A61K38/204 ,  A61K38/2046 ,  A61K38/2086 ,  A61K39/21 ,  A61K2039/5256 ,  C07K14/005 ,  C12N7/00 ,  C12N2740/13043 ,  C12N2740/13045 ,  C12N2740/15041 ,  C12N2740/15043 ,  C12N2740/15045 ,  C12N2770/36122 ,  C12N2770/36134 ,  C12N2810/609 ,  C12N2810/855 ,  Y02A50/386 ,  Y02A50/396 ,  Y02A50/401 ,  Y02A50/403 ,  Y02A50/407 ,  Y02A50/41 ,  Y02A50/412 ,  Y02A50/423 ,  Y02A50/466 ,  Y02A50/475 ,  Y02A50/48 ,  Y02A50/481 ,  Y02A50/492 ,  A61K2300/00

Abstract: Methods and compositions are provided for delivery of a polynucleotide encoding a gene of interest, typically an antigen, to a dendritic cell (DC). The virus envelope comprises a DC-SIGN specific targeting molecule. The methods and related compositions can be used to treat patients suffering from a wide range of conditions, including infection, such as HIV/AIDS, and various types of cancers.

Abstract translation: 提供了将编码感兴趣的基因（通常为抗原）的多核苷酸递送至树突状细胞（DC）的方法和组合物。 病毒包膜包含DC-SIGN特异性靶向分子。 方法和相关组合物可用于治疗患有广泛病症的患者，包括感染，例如HIV / AIDS和各种类型的癌症。

公开(公告)号：US12066430B2

公开(公告)日：2024-08-20

申请号：US16633451

申请日：2018-07-24

Applicant: California Institute of Technology

Inventor： Michael T. Bethune ,  Jocelyn T. Kim ,  David Baltimore ,  Guideng Li ,  Stephanie Wong

IPC: G01N33/50 ,  G01N33/566 ,  G06F16/27

CPC classification number: G01N33/505 ,  G01N33/566 ,  G06F16/27

Abstract: Disclosed herein are trogocytosis based TCR ligand discovery platforms and methods of using the same, trogocytosis based TCR discovery platforms and methods of using the same, and trogocytosis based ligand discovery platforms and methods of using the same. Also disclosed herein are isolated cells, nucleotides, sequences, and sequence databases produced using trogocytosis based discovery platforms.

公开(公告)号：US11846639B2

公开(公告)日：2023-12-19

申请号：US17378310

申请日：2021-07-16

Applicant: THE BOARD OF TRUSTEES OF THE LELAND STANFORD JUNIOR UNIVERSITY ,  CALIFORNIA INSTITUTE OF TECHNOLOGY

Inventor： Michael Edward Birnbaum ,  Juan Luis Mendoza ,  Michael Thomas Bethune ,  David Baltimore ,  Kenan Christopher Garcia

IPC: G01N33/68 ,  C07K14/00

CPC classification number: G01N33/6845 ,  C07K14/00 ,  G01N2333/7051 ,  G01N2333/70539

Abstract: Compositions and methods are provided for the identification of peptide sequences that are ligands for a T cell receptor (TCR) of interest, in a given MHC context.

公开(公告)号：US20210324035A1

公开(公告)日：2021-10-21

申请号：US17273192

申请日：2019-09-04

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

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

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

Abstract: 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.