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16 条记录 (耗时 0.025 秒)

    NOTCH RECEPTORS WITH ZINC FINGER-CONTAINING TRANSCRIPTIONAL EFFECTOR
    1.
    发明申请
    NOTCH RECEPTORS WITH ZINC FINGER-CONTAINING TRANSCRIPTIONAL EFFECTOR 有权

    公开(公告)号：US20220356225A1

    公开(公告)日：2022-11-10

    申请号：US17763122

    申请日：2020-09-23

    申请人： The Regents of the University of California ,  Trustees of Boston University

    发明人： Kole T. ROYBAL ,  Iowis ZHU ,  Raymond LIU ,  Ahmad S. KHALIL ,  Divya ISRANI

    IPC分类号： C07K14/705 ,  C07K16/28 ,  C07K14/725 ,  A61K35/17 ,  C12N5/0783

    摘要： The present disclosure generally relates to, inter alia, a new class of chimeric Notch receptors containing a synthetic zinc finger transcriptional effector (synZTE) module, engineered to modulate gene expression and cellular activities in a ligand-dependent manner. The new Notch receptors surprisingly retain the ability to transduce signals in response to ligand binding despite that the Notch extracellular subunit, which includes the negative regulatory region previously believed to be essential for the functioning of Notch receptors, is partly or completely deleted. In addition, the synZTE is designed to bind orthogonal DNA target sequences in target organisms which in turn facilitates precise regulation of therapeutic gene expression with minimal off-target activity. Also provided are compositions and methods useful for producing such receptors, nucleic acids encoding same, host cells genetically modified with the nucleic acids, as well as methods for modulating an activity of a cell and/or for treatment of various health conditions.

    NOTCH RECEPTORS WITH MINIMAL LINKER
    4.
    发明申请
    NOTCH RECEPTORS WITH MINIMAL LINKER 有权

    公开(公告)号：US20220340637A1

    公开(公告)日：2022-10-27

    申请号：US17762685

    申请日：2020-09-23

    申请人： The Regents of the University of California

    发明人： Kole T. ROYBAL ,  Raymond LIU ,  Iowis ZHU

    IPC分类号： C07K14/705 ,  C07K16/28 ,  A61K35/17 ,  A61P35/02 ,  A61K45/06 ,  A61K39/395 ,  A61K38/17

    摘要： The present disclosure generally relates to, inter alia, a new class of receptors engineered to modulate transcriptional regulation in a ligand-dependent manner. Particularly, the new receptors, even though derived from Notch, do not require the Notch negative regulatory regions previously believed to be essential for the functioning of the receptors. In addition, the new receptors described herein incorporate a flexible polypeptide connector region disposed between the extracellular ligand-binding domain (ECD) and the transmembrane domain (TMD) which facilitates optimizing the stiffness/flexibility of the chimeric polypeptides to achieve a desired activity. The disclosure also provides compositions and methods useful for producing such receptors, nucleic acids encoding same, host cells genetically modified with the nucleic acids, as well as methods for modulating an activity of a cell and/or for the treatment of various health conditions such as diseases (e.g., cancers).

    HUMANIZED NOTCH RECEPTORS WITH HINGE DOMAIN
    5.
    发明公开
    HUMANIZED NOTCH RECEPTORS WITH HINGE DOMAIN 审中-公开

    公开(公告)号：US20230183709A1

    公开(公告)日：2023-06-15

    申请号：US17995751

    申请日：2021-04-08

    申请人： The Regents of the University of California

    发明人： Kole T. ROYBAL ,  Raymond LIU

    IPC分类号： C12N15/113 ,  C07K14/705 ,  C07K16/28 ,  C12N15/86

    CPC分类号： C12N15/1138 ,  C07K14/705 ,  C07K16/2803 ,  C07K16/2878 ,  C12N15/86 ,  A61K2039/505

    摘要： The present disclosure generally relates to, inter alia, a new class of chimeric Notch receptors containing a fully humanized transcriptional effector, engineered to modulate gene expression and cellular activities in a ligand-dependent manner. The new chimeric Notch receptors surprisingly retain the ability to transduce signals in response to ligand binding despite that the Notch extracellular subunit (NEC), which includes the negative regulatory region (NRR) previously believed to be essential for the functioning of Notch receptors is completely absent. In addition, the new receptors described herein incorporate an extracellular oligomerization domain to promote oligomer formation of the chimeric receptors. Also provided are compositions and methods useful for producing such receptors, nucleic acids encoding same, engineered cells genetically modified with the nucleic acids, as well as methods for modulating an activity of a cell and/or for the treatment of various diseases such as cancers.

    NOTCH RECEPTORS WITH HINGE DOMAIN
    7.
    发明申请
    NOTCH RECEPTORS WITH HINGE DOMAIN 有权

    公开(公告)号：US20210268024A1

    公开(公告)日：2021-09-02

    申请号：US17217618

    申请日：2021-03-30

    申请人： The Regents of the University of California

    发明人： Kole T. ROYBAL ,  Raymond Liu ,  Iowis Zhu

    IPC分类号： A61K35/17 ,  A61P35/00 ,  C07K16/28 ,  C07K14/705 ,  C07K16/32

    摘要： The present disclosure generally relates to, inter alia, a new class of receptors engineered to modulate transcriptional regulation in a ligand-dependent manner. Particularly, the new receptors, even though derived from Notch, do not require the Notch negative regulatory regions previously believed to be essential for the functioning of the receptors. In addition, the new receptors described herein incorporate an extracellular oligomerization domain to promote oligomer formation of the chimeric receptors. The disclosure also provides compositions and methods useful for producing such receptors, nucleic acids encoding same, host cells genetically modified with the nucleic acids, as well as methods for modulating an activity of a cell and/or for the treatment of various health conditions such as cancers.