ARTIFICIAL EUKARYOTIC EXPRESSION SYSTEM WITH ENHANCED PERFORMANCES

    公开(公告)号:US20230265479A1

    公开(公告)日:2023-08-24

    申请号:US18017967

    申请日:2021-08-03

    Applicant: EUKARYS

    Inventor: Philippe JAIS

    Abstract: The present invention concerns a method for expressing a recombinant DNA molecule in a eukaryotic host cell, comprising the steps of:



    (a) expressing or introducing at least one chimeric protein, in said host cell, wherein said chimeric protein comprises:

    (i) at least one catalytic domain of a capping enzyme, in particular selected in the group consisting of cap-0 canonical capping enzymes, cap-0 non-canonical capping enzymes, cap-1 capping enzymes and cap-2 capping enzymes; and
    (ii) at least one catalytic domain of a DNA-dependent RNA polymerase, in particular a bacteriophage DNA-dependent RNA polymerase,


    (b) constitutively or transiently downregulating the phosphorylation level of subunit a of translation initiation factor eIF2 (eIF2α) in said host cell.




    The invention also concerns an isolated nucleic acid molecule or a set of nucleic acid molecules, comprising or consisting of (1) at least one nucleic acid sequence encoding a chimeric protein comprising at least one catalytic domain of a capping enzyme; and at least one catalytic domain of a DNA-dependent RNA polymerase; and (2) at least one nucleic acid sequence downregulating the phosphorylation level of eIF2α in a eukaryotic host cell or encoding a polypeptide downregulating said phosphorylation level; and (3) optionally, at least one nucleic acid sequence encoding a poly(A) polymerase, as well as vectors, kits and cells comprising said nucleic acid molecule or set, and different uses and applications thereof.

    COMPOSITIONS AND METHODS FOR THE TREATMENT OF KRABBE AND OTHER NEURODEGENERATIVE DISEASES
    7.
    发明申请
    COMPOSITIONS AND METHODS FOR THE TREATMENT OF KRABBE AND OTHER NEURODEGENERATIVE DISEASES 审中-公开
    治疗KRABBE和其他神经病变疾病的组合物和方法

    公开(公告)号:US20120156180A1

    公开(公告)日:2012-06-21

    申请号:US13390073

    申请日:2010-08-10

    Abstract: Provided are compositions and methods for the treatment of Krabbe and other neurodegenerative diseases, including storage diseases such as GM1 gangliosidosis, Niemann-Pick disease, Tay-Sachs disease, Sandhoff disease, metachromatic leukodystrophy, Canavan disease, Pelizaeus-Merzbacher disease, and storage conditions facilitated by aging of lysosomal functions, which are associated with psychosine (and/or other storage material)-mediated axonal degeneration. Compositions and methods employ (1) one or more inhibitor of a phos-photransferase activity of one or more kinase(s) such as, for example, CDK5, P38, jnk, src, CK2, PKC, GSK3α and β; (2) one or more inhibitor of a phosphotransferase activity of one or more phosphatase(s) such as, for example, the Ser/Thr protein phosphatase PP1 and Tyr protein phosphatase PP2; one or more inhibitor of a caspase/calpain activity of one or more caspases such as caspase 3 and calpains such as calpain 1 and 2; and (4) one or more inhibitor of a sodium/calcium exchange protein such as, for example, NCX1. Inhibitors include small molecules, including the GSK3β inhibitor L803 and the NCX1 inhibitor flecainide, and siRNA molecules that downmodulate cellular levels of one or more mRNA, including siRNA that are capable of downmodulating the cellular expression of PP1. Inhibitors disclosed can cross the blood-brain barrier and, thus, are available to the central nervous system (CNS) and effective in reducing psychosine-mediated axonal degeneration.

    Abstract translation: 提供了用于治疗Krabbe和其它神经变性疾病的组合物和方法,包括存储疾病如GM1神经节苷脂病,尼曼皮克病,泰萨病,桑德霍夫病,异染色性脑白质营养不良症,卡纳万病,Pelizaeus-Merzbacher病和储存条件 通过与精神病(和/或其他储存材料)介导的轴索变性相关的溶酶体功能的老化促进。 组合物和方法使用(1)一种或多种一种或多种激酶(例如CDK5,P38,jnk,src,CK2,PKC,GSK3α和bgr)的磷酸转移酶活性的抑制剂。 (2)一种或多种一种或多种磷酸酶的磷酸转移酶活性的抑制剂,例如Ser / Thr蛋白磷酸酶PP1和Tyr蛋白磷酸酶PP2; 一种或多种胱天蛋白酶/钙蛋白酶活性的一种或多种胱天蛋白酶抑制剂,例如胱天蛋白酶3和钙蛋白酶如钙蛋白酶1和2; 和(4)一种或多种钠/钙交换蛋白抑制剂,例如NCX1。 抑制剂包括小分子,包括GSK3&bgr; 抑制剂L803和NCX1抑制剂flecainide,以及下调调节一种或多种mRNA的细胞水平的siRNA分子,包括能够下调PP1细胞表达的siRNA。 所公开的抑制剂可以穿过血脑屏障,因此可用于中枢神经系统(CNS),并有效减少精神病介导的轴索变性。

    DSP-10 DUAL-SPECIFICITY PHOSPHATASE
    8.
    发明申请
    DSP-10 DUAL-SPECIFICITY PHOSPHATASE 审中-公开
    DSP-10双特异性磷酸酯酶

    公开(公告)号:US20080138347A1

    公开(公告)日:2008-06-12

    申请号:US11866369

    申请日:2007-10-02

    Abstract: Compositions and methods are provided for the treatment of conditions associated with cell proliferation, cell differentiation and cell survival. In particular, the dual-specificity phosphatase DSP-10, and polypeptide variants thereof that stimulate dephosphorylation of DSP-10 substrates, are provided. The polypeptides may be used, for example, to identify antibodies and other agents that inhibit DSP-10 activity. The polypeptides and agents may be used to modulate cell proliferation, differentiation, and survival.

    Abstract translation: 提供组合物和方法用于治疗与细胞增殖,细胞分化和细胞存活相关的病症。 特别地,提供了刺激DSP-10底物去磷酸化的双特异性磷酸酶DSP-10及其多肽变体。 多肽可用于例如鉴定抑制DSP-10活性的抗体和其它试剂。 多肽和试剂可用于调节细胞增殖,分化和存活。

    Methods of identifying an agent capable of interfering with Rad9 dephosphorylation
    9.
    发明授权
    Methods of identifying an agent capable of interfering with Rad9 dephosphorylation 有权
    鉴定能够干扰Rad9去磷酸化的试剂的方法

    公开(公告)号:US07384761B2

    公开(公告)日:2008-06-10

    申请号:US10220375

    申请日:2001-03-02

    Applicant: Ying Luo Xiang Xu

    Inventor: Ying Luo Xiang Xu

    Abstract: The present invention is directed to novel polypeptides, nucleic acids and related molecules which have an effect on or are related to the cell cycle. Also provided herein are vectors and host cells polypeptides of the present invention fused to heterologous polypeptide sequences, antibodies which bind to the polypeptides of the present invention and to methods for producing the polypeptides of the present invention. Further provided by the present invention are methods for identifying novel compositions which mediate cell cycle bioactivity, and the use of such compositions in diagnosis and treatment of disease.

    Abstract translation: 本发明涉及对细胞周期有影响或与细胞周期有关的新型多肽,核酸和相关分子。 本文还提供了与异源多肽序列融合的本发明的载体和宿主细胞多肽,与本发明的多肽结合的抗体和用于产生本发明的多肽的方法。 本发明还提供了鉴定介导细胞周期生物活性的新型组合物的方法,以及这些组合物在疾病诊断和治疗中的应用。

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