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    MODIFIED SHIGELLA APYRASE AND USES THEREOF
    5.
    发明公开
    MODIFIED SHIGELLA APYRASE AND USES THEREOF 审中-公开

    公开(公告)号：US20240167005A1

    公开(公告)日：2024-05-23

    申请号：US18282415

    申请日：2022-03-15

    申请人： APIRAYS BIOSCIENCES AB

    发明人： Pavankumar ASALAPURAM RAMACHANDRAN ,  Nikhil SANGITH

    IPC分类号： C12N9/14 ,  C12Q1/34 ,  C12Q1/6869

    CPC分类号： C12N9/14 ,  C12Q1/34 ,  C12Q1/6869 ,  C12Y306/01005

    摘要： An apyrase enzyme, characterized by that the apyrase comprises a polypeptide sequence having at least 70% sequence identity to the wild-type Shigella flexneri apyrase of SEQ ID NO:1, wherein said sequence differs from SEQ ID NO:1 at least in that the sequence comprises at least one amino-acid substitution of a residue aligning with a residue selected from: F53, L66 and E77; and the apyrase catalyzes the dephosphorylation of at least one organic phosphate with at least 10-fold lower Km compared to the apyrase of SEQ ID NO:1. Uses of said apyrase in ATP elimination and dephosphorylation of organic phosphates.

    Rat models for CMT2A that develop a progressive neuropathy
    10.
    发明公开
    Rat models for CMT2A that develop a progressive neuropathy 审中-公开

    公开(公告)号：US20240074416A1

    公开(公告)日：2024-03-07

    申请号：US18368130

    申请日：2023-09-14

    申请人： Charcot-Marie-Tooth Association ,  The Trustees of the University of Pennsylvania

    发明人： Mark Albert Scheideler ,  Guojun Zhao ,  John Svaren ,  David C. Chan ,  Steven S. Scherer ,  Taleen Hanania

    IPC分类号： A01K67/027 ,  C12N9/14

    CPC分类号： A01K67/0278 ,  C12N9/14 ,  A01K2217/075 ,  A01K2227/105 ,  A01K2267/0356 ,  C12Y306/05

    摘要： The present invention relates to the engineering an animal model, preferably mammalian models, more preferably a rat model representing Charcot-Marie-Tooth disease 2A (CMT2A) harboring the p.Arg364Trp or p.His361Tyr Mfn2 mutation, whose human counterpart results in a severe, early-onset axonal neuropathy. A model having the p.Arg364Trp Mfn2 mutation is based on a mutation made using zinc finger endonuclease technology in fertilized rat eggs. Cohorts of mutants and wild type littermates were characterized behaviorally and shown to develop multiple motor deficits that worsened over time. Separate cohorts of mutant and wild type rats sacrificed at 7, 40, and 48 weeks and analyzed by light microscopy showed a reduced density of myelinated axons and active axonal degeneration in distal but not proximal nerves, as well as axonal degeneration in the fasciculus gracilis of the cervical spinal cord at 40 and 48 weeks. These findings were not present in the 7-week-old cohort of Mfn2 mutants, or in wild type rats at 7 or 40 weeks. A model having the p.His361Tyr Mfn2 mutation is based on a mutation made using CRISPR/Cas9 gene editing technology. This mutation showed abnormalities in gait dynamics at 8 weeks and a lengthening of the gait cycle at 16 weeks. A genetically authentic animal model for CMT2A developing a progressive axonal neuropathy is a valuable tool for examining the pathogenesis and treatment of CMT2A.