UREOHYDROLASES AS DOMINANT SELECTABLE MARKERS IN YEAST

    公开(公告)号:US20170298368A1

    公开(公告)日:2017-10-19

    申请号:US15301599

    申请日:2015-04-13

    IPC分类号: C12N15/81 C12N9/78 C12Q1/04

    摘要: The invention relates to a nucleic acid molecule encoding a novel selection marker. Said marker is a guanidinobutyrase from Kluyveromyces lactis, which, when expressed in Saccharomyces, allows the growth of the yeast in the presence of guanidinobutyrate as the sole nitrogen source. Said marker can be used in a method for producing a microorganism having an altered genome. The invention further relates to a set of constructs, comprising a first construct comprising a recognition site for an endonuclease, a first region of homology with a target gene of a microorganism, and a first part of a nucleotide sequence encoding the selection marker, and a second construct comprising a second part of the nucleotide sequence encoding the selection marker, a second region of homology with the target gene of the microorganism, and a copy of the endonuclease recognition site. The invention further relates to methods for altering a target gene in a microorganism, to methods for producing a microorganism, and to microorganisms that are produced by the methods of the invention.

    Human autoantibodies specific for PAD3 which are cross-reactive with PAD4 and their use in the diagnosis and treatment of rheumatoid arthritis and related diseases
    7.
    发明授权
    Human autoantibodies specific for PAD3 which are cross-reactive with PAD4 and their use in the diagnosis and treatment of rheumatoid arthritis and related diseases 有权
    与PAD4交叉反应的PAD3特异性的人类自身抗体及其在类风湿性关节炎和相关疾病的诊断和治疗中的应用

    公开(公告)号:US08975033B2

    公开(公告)日:2015-03-10

    申请号:US14071996

    申请日:2013-11-05

    IPC分类号: G01N33/53 G01N33/564

    摘要: In one or more embodiments, the present invention provides a novel biomarker which provides a link between a distinct clinical phenotype and a biochemical effect of an autoantibody on an enzyme implicated in disease pathogenesis. In particular, the present invention provides an isolated or purified human autoantibody to PAD3 protein. Methods of diagnosis of subjects for rheumatoid arthritis (RA) using these antibodies as well as diagnosis of the severity of RA in the subject, and methods for monitoring treatment of a subject with RA are also provided. The biomarkers provided herein are also useful in the diagnosis of connective tissue-interstitial lung disease (CT-ILD) in patients having or suspected of having RA.

    摘要翻译: 在一个或多个实施方案中,本发明提供了一种新的生物标志物,其提供不同临床表型与自身抗体对涉及疾病发病机理的酶的生物化学作用之间的联系。 特别地,本发明提供了PAD3蛋白的分离或纯化的人自身抗体。 还提供了使用这些抗体诊断类风湿性关节炎(RA)的受试者的方法以及受试者中RA的严重程度的诊断,以及用RA监测受试者的治疗方法。 本文提供的生物标志物也可用于诊断具有或怀疑具有RA的患者的结缔组织间质性肺病(CT-ILD)。

    HUMAN AUTOANTIBODIES SPECIFIC FOR PAD3 WHICH ARE CROSS-REACTIVE WITH PAD4 AND THEIR USE IN THE DIAGNOSIS AND TREATMENT OF RHEUMATOID ARTHRITIS AND RELATED DISEASES
    8.
    发明申请
    HUMAN AUTOANTIBODIES SPECIFIC FOR PAD3 WHICH ARE CROSS-REACTIVE WITH PAD4 AND THEIR USE IN THE DIAGNOSIS AND TREATMENT OF RHEUMATOID ARTHRITIS AND RELATED DISEASES 有权
    PAD4与PAD4交叉反应的人体免疫球蛋白特异性及其在诊断和治疗恶病质和相关疾病中的应用

    公开(公告)号:US20140127720A1

    公开(公告)日:2014-05-08

    申请号:US14071996

    申请日:2013-11-05

    IPC分类号: G01N33/68

    摘要: In one or more embodiments, the present invention provides a novel biomarker which provides a link between a distinct clinical phenotype and a biochemical effect of an autoantibody on an enzyme implicated in disease pathogenesis. In particular, the present invention provides an isolated or purified human autoantibody to PAD3 protein. Methods of diagnosis of subjects for rheumatoid arthritis (RA) using these antibodies as well as diagnosis of the severity of RA in the subject, and methods for monitoring treatment of a subject with RA are also provided. The biomarkers provided herein are also useful in the diagnosis of connective tissue-interstitial lung disease (CT-ILD) in patients having or suspected of having RA.

    摘要翻译: 在一个或多个实施方案中,本发明提供了一种新的生物标志物,其提供不同临床表型与自身抗体对涉及疾病发病机理的酶的生物化学作用之间的联系。 特别地,本发明提供了PAD3蛋白的分离或纯化的人自身抗体。 还提供了使用这些抗体诊断类风湿性关节炎(RA)的受试者的方法以及受试者中RA的严重程度的诊断,以及用RA监测受试者的治疗方法。 本文提供的生物标志物也可用于诊断具有或怀疑具有RA的患者的结缔组织间质性肺病(CT-ILD)。

    METHOD FOR ASSESSING THE ABILITY OF A PATIENT TO RESPOND TO OR BE SAFELY TREATED BY A NUCLEOSIDE ANALOG BASED-CHEMOTHERAPY
    9.
    发明申请
    METHOD FOR ASSESSING THE ABILITY OF A PATIENT TO RESPOND TO OR BE SAFELY TREATED BY A NUCLEOSIDE ANALOG BASED-CHEMOTHERAPY 审中-公开
    用于评估患者反应或由核苷类似物基因治疗完全治疗的能力的方法

    公开(公告)号:US20130011392A1

    公开(公告)日:2013-01-10

    申请号:US13510705

    申请日:2010-11-19

    摘要: The invention relates to an in vitro method for determining the ability of a patient with cancer to respond to a monochemotherapy or to a polychemotherapy involving the administration of at least one chemotherapeutic agent the liver elimination of which involves cytidine deaminase (CDA), or to be treated by at least one such chemotherapeutic agent, which method comprises determining the CDA activity in a biological sample of the patient, wherein a CDA activity above 6 U/mg of serum sample total protein is indicative of the inability of the patient to respond to the chemotherapy, a CDA activity between 1.1 U/mg and 6 U/mg of serum sample total protein is indicative of the ability of the patient to be treated by the chemotherapeutic agent when said agent is administered in the context of a monochemotherapy, and a CDA activity between 1.4 U/mg and 6 U/mg of serum sample total protein is indicative of the ability of the patient to be treated by the chemotherapeutic agent when said agent is administered in the context of a polychemotherapy.

    摘要翻译: 本发明涉及一种用于确定癌症患者对单次疗法或多化疗的能力的体外方法,所述多化疗包括施用至少一种涉及胞苷脱氨酶(CDA)的肝脏消除的化学治疗剂,或者为 由至少一种这样的化学治疗剂治疗,该方法包括确定患者生物样品中的CDA活性,其中高于6U / mg的血清样品总蛋白的CDA活性指示患者不能对 化学疗法,1.1U / mg和6U / mg血清样品总蛋白之间的CDA活性指示当所述药物在单次疗法的上下文中时,由化学治疗剂治疗的患者的能力,以及CDA 1.4U / mg和6U / mg的血清样品总蛋白之间的活性指示当所述药剂是所述药物时,由化学治疗剂治疗的患者的能力 在多化学治疗的背景下进行治疗。

    APOBEC3 MEDIATED DNA EDITING
    10.
    发明申请
    APOBEC3 MEDIATED DNA EDITING 有权
    APOBEC3介导的DNA编码

    公开(公告)号:US20090260090A1

    公开(公告)日:2009-10-15

    申请号:US12100212

    申请日:2008-04-09

    摘要: The present invention relates to methods and compositions for preventing the occurance or progression of a cancer or pre-cancerous condition associated with expression, or over-expression of human cytidine deaminases of the APOBEC3 family. The invention also relates to drug screening assays designed to identify compounds that regulate the activity, or level of expression, of hA3A, hA3C and hA3H. The invention further relates to transgenic mice, as well as cells derived from said mice, that have been genetically engineered to express, or over-express hA3A, hA3C and/or hA3H. Such mice may be utilized to screen for, or identify, compounds that modulate the activity, or expression, of the human cytidine deaminases. The present invention also provides topical compositons such as cosmetic lotion, crème, or sunscreen for use on the skin, which comprise one or more inhibitors of human cytidine deaminase activity. The present invention relates to a double stranded DNA obtained following opening up of its duplex structure, said DNA being edited with cellular protein normally or abnormally expressed in the nucleus of an eukaryotic cell. The mono stranded DNA derived from the said double stranded DNA is a part of the present invention.

    摘要翻译: 本发明涉及用于预防与APOBEC3家族的人胞苷脱氨酶的表达或过度表达相关的癌症或癌前病症的发生或进展的方法和组合物。 本发明还涉及设计用于鉴定调节hA3A,hA3C和hA3H的活性或表达水平的化合物的药物筛选测定。 本发明进一步涉及转基因小鼠以及源自所述小鼠的细胞,其已被遗传工程化以表达或过表达hA3A,hA3C和/或hA3H。 这些小鼠可用于筛选或鉴定调节人胞苷脱氨酶活性或表达的化合物。 本发明还提供局部组合物,例如用于皮肤的化妆品洗剂,奶油或防晒剂,其包含一种或多种人胞苷脱氨酶活性的抑制剂。 本发明涉及在其双链体结构开放后获得的双链DNA,所述DNA通过在真核细胞核中正常或异常表达的细胞蛋白进行编辑。 衍生自所述双链DNA的单链DNA是本发明的一部分。