NUCLEIC ACID THERAPEUTICS FOR GENETIC DISORDERS

    公开(公告)号:US20220096525A1

    公开(公告)日:2022-03-31

    申请号:US17378580

    申请日:2021-07-16

    摘要: Provided herein, are compositions based on retroviruses (e.g., lentiviruses) comprising one or more nucleic acid molecules encoding retroviral Pol polyprotein components and a nucleic acid molecule comprising one or more transgene sequences flanked by long terminal repeat sequences, for delivery of the one or more transgenes to a target cell ex vivo or in vivo. The compositions are useful for delivering to a target cell (e.g., hematopoietic stem cells (HSCs), liver cells, ocular cells, muscle cells, epithelial cells, T cells, etc.) and/or stably expressing any transgene (e.g., beta-globin, Factor VIII, RP GTPase regulator (RPGR), dystrophin, cystic fibrosis transmembrane conductance regulator (CFTR), a chimeric antigen receptor, etc.) with a biological effect to treat and/or ameliorate the symptoms associated with any disorder related to gene expression (e.g., sickle cell disease, beta-thalassemia, haemophilia B, retinitis pigmentosa, Duchenne muscular dystrophy, cystic fibrosis, cancer, etc.).

    CONTROL OF METABOLIC FLUX IN CELL-FREE BIOSYNTHETIC SYSTEMS
    9.
    发明申请
    CONTROL OF METABOLIC FLUX IN CELL-FREE BIOSYNTHETIC SYSTEMS 审中-公开
    无细胞生物体系中代谢通量的控制

    公开(公告)号:US20160115558A1

    公开(公告)日:2016-04-28

    申请号:US14895992

    申请日:2014-06-05

    发明人: James R. Swartz

    IPC分类号: C12Q3/00

    CPC分类号: C12Q3/00 C12N9/00

    摘要: Methods are provided for controlling metabolic flux rate in a cell-free system comprising a complex set of enzymes, to produce a desired product of a pathway of interest. In the methods of the invention, measurements of metabolic performance parameters are taken by continuous monitoring or intermittent monitoring. Based on the metabolic performance parameters, the system is modified by one or more steps comprising: (i) altering enzyme levels in the cell-free system; (ii) altering feed rate of a substrate that controls redox flux or carbon flux to the cell-free system; (iii) altering O2 addition to the cell-free system; (iv) controlling efficiency of electron transport system by altering leakage across a membrane; wherein enzymes present in the pathway of interest catalyze production of a desired product.

    摘要翻译: 提供了用于控制包含复杂的酶组的无细胞系统中的代谢通过速率的方法,以产生感兴趣的途径的所需产物。 在本发明的方法中,通过连续监测或间歇监测进行代谢性能参数的测量。 基于代谢性能参数,系统通过一个或多个步骤修饰,包括:(i)改变无细胞系统中的酶水平; (ii)将控制氧化还原通量或碳通量的底物的进料速率改变为无细胞系统; (iii)改变无细胞系统中的O2添加; (iv)通过改变膜上的渗漏来控制电子传输系统的效率; 其中存在于感兴趣途径中的酶催化产生所需产物。

    METHODS FOR CONTROL OF FLUX IN METABOLIC PATHWAYS THROUGH PROTEASE MANIPULATION
    10.
    发明申请
    METHODS FOR CONTROL OF FLUX IN METABOLIC PATHWAYS THROUGH PROTEASE MANIPULATION 审中-公开
    通过蛋白质调控控制代谢途径中的通量的方法

    公开(公告)号:US20150064751A1

    公开(公告)日:2015-03-05

    申请号:US14542074

    申请日:2014-11-14

    发明人: James R. Swartz

    IPC分类号: C12N9/50 C12P7/42 C12N15/70

    摘要: The embodiments described herein pertain to cells, and methods for preparing cells, that can be used as biocatalysts by altering enzymes that compete for a substrate or product of a pathway of interest such that the targeted enzyme is sensitive to a site-specific protease, which protease is expressed but relocated in the cell to a site where it is not in contact with the targeted enzyme in the intact cell. Upon cell lysis, the protease contacts the target enzyme, which is then inactivated by protease cleavage.

    摘要翻译: 本文描述的实施方案涉及细胞和用于制备细胞的方法,其可以通过改变竞争基底或感兴趣途径的产物的酶使其用作生物催化剂,使得靶向酶对位点特异性蛋白酶敏感,其中 蛋白酶被表达,但是在细胞中重新定位到与完整细胞中的目标酶不接触的位点。 细胞裂解后,蛋白酶与靶酶接触,然后通过蛋白酶切割失活。