公开(公告)号：US08361982B2

公开(公告)日：2013-01-29

申请号：US12769157

申请日：2010-04-28

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

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

IPC: A01N43/04 ,  C12Q1/68 ,  C12N15/00 ,  C12P19/34 ,  C07H21/04

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.

公开(公告)号：US20120322854A1

公开(公告)日：2012-12-20

申请号：US13526347

申请日：2012-06-18

Applicant: Aadel Chaudhuri ,  Alex Steven So ,  David Baltimore ,  Ryan M. O'Connell

Inventor： Aadel Chaudhuri ,  Alex Steven So ,  David Baltimore ,  Ryan M. O'Connell

IPC: A61K31/7088 ,  A61P1/00 ,  A61P19/02 ,  A61P25/00

CPC classification number: A61K31/7088

Abstract: The present disclosure relates to regulation of macrophage activation by delivering of miRNAs, for example miR-125b or anti-miR-125b, to macrophages. For example, in some embodiments, macrophage activation can be elevated or reduced by administering miR-125b or anti-miR-125b oligonucleotides. Also disclosed are methods for promoting T cell activation and method for treating various disorders such as tumor and autoimmune diseases.

Abstract translation: 本公开涉及通过将巨噬细胞递送miRNA（例如miR-125b或抗miR-125b）来调节巨噬细胞活化。 例如，在一些实施方案中，可通过施用miR-125b或抗miR-125b寡核苷酸来升高或降低巨噬细胞活化。 还公开了用于促进T细胞活化的方法和用于治疗各种疾病如肿瘤和自身免疫性疾病的方法。

公开(公告)号：US20120065245A1

公开(公告)日：2012-03-15

申请号：US13230673

申请日：2011-09-12

Applicant: David Baltimore ,  Ryan M. O'Connell

Inventor： David Baltimore ,  Ryan M. O'Connell

IPC: A61K31/7088 ,  A61P35/02 ,  A61P35/00 ,  A61P7/06 ,  A61P7/00

CPC classification number: A61K31/7105 ,  C12N2310/141

Abstract: The present disclosure relates to regulation of functions of hematopoietic stem cells (HSCs) by delivering of miRNAs, including miR-125b, miR-126, and miR-155, to HSCs. For example, in some embodiments, blood output in a mammal can be increased by administering miR-125b, miR-126, and/or miR-155 oligonucleotides. Also disclosed are methods for promoting hematopoietic stem cell engraftment and method for treating a myeloproliferative disorder.

Abstract translation: 本公开涉及通过向HSC递送miRNA（包括miR-125b，miR-126和miR-155）来调节造血干细胞（HSC）的功能。 例如，在一些实施方案中，可以通过施用miR-125b，miR-126和/或miR-155寡核苷酸来增加哺乳动物的血液输出。 还公开了促进造血干细胞移植的方法和治疗骨髓增生性疾病的方法。

公开(公告)号：US20100203630A1

公开(公告)日：2010-08-12

申请号：US12622379

申请日：2009-11-19

Applicant: Xin Luo ,  Lili Yang ,  David Baltimore

Inventor： Xin Luo ,  Lili Yang ,  David Baltimore

IPC: C12N5/10 ,  C12N5/0781

CPC classification number: C12N5/0635 ,  C07K16/00 ,  C07K16/1036 ,  C07K16/1045 ,  C12N2501/056 ,  C12N2501/125 ,  C12N2501/145 ,  C12N2501/22 ,  C12N2501/23 ,  C12N2501/26 ,  C12N2501/52 ,  C12N2502/1394 ,  C12N2510/02

Abstract: The present disclosure relates to systems, methods and compositions for the generation of antibody-producing B cells in vitro. Some embodiments are related to an in vitro system for generating antibody-producing B cells from hematopoietic stem/progenitor cells (HSPCs).

Abstract translation: 本公开涉及用于在体外产生产生抗体的B细胞的系统，方法和组合物。 一些实施方案涉及用于从造血干细胞/祖细胞（HSPC）产生产生抗体的B细胞的体外系统。

公开(公告)号：US07732207B2

公开(公告)日：2010-06-08

申请号：US11689407

申请日：2007-03-21

Applicant: Xiao-Feng Qin ,  David Baltimore ,  Irvin S. Y. Chen ,  Dong Sung An

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

IPC: C12Q1/68 ,  C12P19/34 ,  C12N15/87 ,  C07H21/02 ,  C07H21/04

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: 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). The methods can be used to express double stranded RNA complexes. Small interfering RNA (siRNA) can be expressed using the methods of the invention within a cell, that interfere with a viral life cycle by down regulating either the viral genome, a viral genome transcript, or a host cell that. In another aspect the invention provides methods for treating patients having suffering from infection, particularly infection with HIV. In a further aspect, the invention provides methods for producing siRNA encoding lentivirus where the siRNA activity may interfere with the lentiviral life cycle.

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）。 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），其通过下调病毒基因组，病毒基因组转录物或宿主细胞来干扰病毒生命周期。 另一方面，本发明提供了治疗患有感染，特别是HIV感染的患者的方法。 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。

公开(公告)号：US07732193B2

公开(公告)日：2010-06-08

申请号：US10243816

申请日：2002-09-13

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

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

IPC: C12N15/00 ,  C12N15/63 ,  C12Q1/68 ,  C12P19/34 ,  C07H21/04

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：US20100120122A1

公开(公告)日：2010-05-13

申请号：US12688689

申请日：2010-01-15

Applicant: Pin Wang ,  Lili Yang ,  David Baltimore

Inventor： Pin Wang ,  Lili Yang ,  David Baltimore

IPC: C12N7/01

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：US07323619B2

公开(公告)日：2008-01-29

申请号：US10243820

申请日：2002-09-13

Applicant: David Baltimore ,  Elizabeth J. Hong ,  Carlos Lois-Caballe ,  Shirley Pease

Inventor： David Baltimore ,  Elizabeth J. Hong ,  Carlos Lois-Caballe ,  Shirley Pease

IPC: C12N15/00 ,  C12N15/86 ,  C12N15/02 ,  A01K67/027 ,  C07H21/04

CPC classification number: C12N15/86 ,  A01K2217/05 ,  A01K2227/30 ,  A01K2227/40 ,  A61K38/00 ,  A61K48/00 ,  C12N15/1132 ,  C12N15/1138 ,  C12N15/8509 ,  C12N2310/111 ,  C12N2310/14 ,  C12N2310/53 ,  C12N2330/30 ,  C12N2740/16043 ,  C12N2800/60 ,  C12N2830/003 ,  C12N2830/006 ,  C12N2830/008 ,  C12N2830/48 ,  C12N2830/85 ,  C12N2840/20 ,  C12N2840/203 ,  C12N2840/44 ,  Y02A50/463 ,  Y02A50/465

Abstract: The present invention relates to methods for producing transgenic animals, particularly transgenic birds and fish, using retroviral constructs engineered to carry the transgene(s) of interest.

Abstract translation: 本发明涉及用转基因动物，特别是转基因鸟类和鱼来生产转基因动物的方法，所述方法使用工程改造来携带感兴趣的转基因的逆转录病毒构建体。

公开(公告)号：US20070232553A1

公开(公告)日：2007-10-04

申请号：US11690105

申请日：2007-03-22

Applicant: David Baltimore ,  Mark Boldin ,  Konstantin Taganov

Inventor： David Baltimore ,  Mark Boldin ,  Konstantin Taganov

IPC: A61K48/00

CPC classification number: C12N15/1137 ,  C12N15/113 ,  C12N2310/111 ,  C12N2310/13 ,  C12N2310/14 ,  C12N2330/10

Abstract: The present disclosure relates to the finding that microRNA-146 plays a role modulating the innate immune response. Innate immunity receptor signaling can be modulated by delivery of microRNA-146 (miR-146) or antisense miR-146 to target immune cells. In some embodiments, IL-1 receptor associated kinase 1 (IRAK1) and TNF receptor associated factor 6 (TRAF6) expression levels are downregulated in a target cell by administering a miR-146 oligonucleotide. Modulation of the innate immune system through miR-146 can be used to treat a variety of diseases and disorders associated with activation of the innate immune system, such as sepsis and Crohn's disease.

Abstract translation: 本公开涉及微RNA-146起调节先天免疫应答的作用的发现。 可以通过将microRNA-146（miR-146）或反义miR-146递送至靶免疫细胞来调节先天免疫受体信号传导。 在一些实施方案中，通过施用miR-146寡核苷酸，在靶细胞中下调IL-1受体相关激酶1（IRAK1）和TNF受体相关因子6（TRAF6）表达水平。 通过miR-146调节先天免疫系统可用于治疗与先天性免疫系统的活化相关的各种疾病和病症，例如败血症和克罗恩病。

公开(公告)号：US20070116690A1

公开(公告)日：2007-05-24

申请号：US11517814

申请日：2006-09-08

Applicant: Lili Yang ,  Luk Parijs ,  David Baltimore

Inventor： Lili Yang ,  Luk Parijs ,  David Baltimore

IPC: A61K48/00 ,  C12N15/867 ,  C12N5/08 ,  C12N5/10

CPC classification number: C12N5/0636 ,  A01K67/0271 ,  A61K39/0011 ,  A61K2039/5156 ,  C07K14/7051 ,  C12N2510/00 ,  C12N2799/027 ,  C12N2840/203

Abstract: The invention provides systems and methods for the generation of lymphocytes having a unique antigen specificity. In a preferred embodiment, the invention provides methods of virally infecting cells from bone marrow with one or more viral vectors that encode antigen-specific antibodies for the production of, for example B cells and T cells. In some embodiments, the viral vectors include an IRES or 2A element to promote separation of, for example, the α subunit and β subunit of a T cell receptor (TCR) or heavy and light chains of a B-cell antibody. The resulting lymphocytes, express the particular antibody that was introduced in the case of B cells and TCR in the case of T cells. The lymphocytes generated can be used for a variety of therapeutic purposes including the treatment of various cancers and the generation of a desired immune response to viruses and other pathogens. The resulting cells develop normally and respond to antigen both in vitro and in vivo. We also show that it is possible to modify the function of lymphocytes by using stem cells from different genetic backgrounds. Thus our system constitutes a powerful tool to generate desired lymphocyte populations both for research and therapy. Future applications of this technology may include treatments for infectious diseases, such as HIV/AIDS, cancer therapy, allergy, and autoimmune disease.

Abstract translation: 本发明提供用于产生具有独特抗原特异性的淋巴细胞的系统和方法。 在优选的实施方案中，本发明提供了用编码抗原特异性抗体以生产例如B细胞和T细胞的一种或多种病毒载体病毒感染骨髓细胞的方法。 在一些实施方案中，病毒载体包括促进分离例如T细胞受体（TCR）的α亚基和β亚基或B细胞抗体的重链和轻链的IRES或2A元件。 在T细胞的情况下，产生的淋巴细胞表达在B细胞和TCR的情况下引入的特异性抗体。 所产生的淋巴细胞可用于各种治疗目的，包括治疗各种癌症和产生对病毒和其它病原体的所需免疫应答。 所得细胞正常发育并在体外和体内对抗原起反应。 我们还表明可以通过使用不同遗传背景的干细胞修饰淋巴细胞的功能。 因此，我们的系统构成了用于研究和治疗产生所需淋巴细胞群体的有力工具。 该技术的未来应用可能包括传染病治疗，如艾滋病毒/艾滋病，癌症治疗，过敏和自身免疫性疾病。