Genetically-modified cells comprising a modified human t cell receptor alpha constant region gene
AssigneePrecision BioSciences, Inc.
InventorsDerek Jantz, James Jefferson Smith, Michael G. Nicholson, Daniel T. MacLeod, Jeyaraj Antony, Victor Bartsevich
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Abstract
Disclosed herein is a genetically-modified cell comprising in its genome a modified human T cell receptor alpha constant region gene, wherein the cell has reduced cell-surface expression of the endogenous T cell receptor. The present disclosure further relates to methods for producing such a genetically-modified cell, and to methods of using such a cell for treating a disease in a subject.
Claims18
-69. (canceled)
A recombinant meganuclease comprising an amino acid sequence set forth in any one of SEQ ID NOs:
- 8-27.
A method for producing a genetically-modified human T cell comprising a modified human TCR alpha constant region gene, said method comprising introducing into a human T cell:
- (a) a first nucleic acid comprising a sequence encoding said recombinant meganuclease of claim 1, wherein said recombinant meganuclease is expressed in said human T cell and generates a cleavage site in the T cell receptor (TCR) alpha constant region gene which is endogenous to said human T cell at a recognition sequence consisting of SEQ ID NO:
- 3;
- and
- (b) a second nucleic acid comprising an exogenous polynucleotide, wherein said exogenous polynucleotide comprises a nucleic acid sequence encoding a chimeric antigen receptor;
- wherein said exogenous polynucleotide encoding said chimeric antigen receptor is inserted into said TCR alpha constant region gene at said cleavage site to generate said genetically-modified human T cell;
- and wherein said genetically-modified human T cell expresses said chimeric antigen receptor on the cell-surface;
- and wherein said genetically-modified human T cell does not express an endogenous TCR on the cell-surface.
A method for producing a genetically-modified human T cell, said method comprising introducing into a human T cell a nucleic acid comprising a sequence encoding said recombinant meganuclease of claim 1;
- wherein said recombinant meganuclease is expressed in said human T cell and generates a cleavage site in the T cell receptor (TCR) alpha constant region gene which is endogenous to said human T cell at a recognition sequence consisting of SEQ ID NO:
- 3;
- and wherein said genetically-modified human T cell does not express an endogenous TCR on the cell-surface.
Dependencies are inferred from the claim text.