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.

公开(公告)号：US20230174612A1

公开(公告)日：2023-06-08

申请号：US17995765

申请日：2021-03-24

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 ,  A61K35/17 ,  C12N15/86

CPC分类号： C07K14/705 ,  C07K14/70517 ,  C07K16/2803 ,  A61K35/17 ,  C12N15/86 ,  C07K2319/81 ,  C07K2317/622 ,  C07K2319/03 ,  C07K2319/035 ,  C07K2317/24 ,  C07K2319/715 ,  C12N2740/15043

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 (NEC), which includes the negative regulatory region (NRR) 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 the treatment of various health conditions such as cancers.

公开(公告)号：US20200377564A1

公开(公告)日：2020-12-03

申请号：US16875591

申请日：2020-05-15

申请人： TRUSTEES OF BOSTON UNIVERSITY

发明人： Ahmad S. KHALIL ,  Wilson Wai Chun WONG ,  Divya ISRANI ,  Huishan LI

IPC分类号： C07K14/47

摘要： The technology described herein is directed to regulated synthetic gene expression systems. In one aspect described herein are synthetic transcription factors (synTFs) comprising a DNA binding domain, a transcriptional effector domain, and a regulator protein. In other aspects described herein are gene expression systems comprising said synTFs and methods of treating diseases and disorders using said synTFs.