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. McLeod, 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.
Claims10
1-21. (canceled)
A method for producing a genetically-modified human T cell comprising a modified human T cell receptor (TCR) alpha constant region gene, said method comprising:
- (a) introducing into a human T cell:
- (i) a first polynucleotide comprising a nucleic acid sequence encoding an engineered meganuclease, wherein said engineered meganuclease is expressed in said human T cell;
- or
- (ii) an engineered meganuclease protein;
- wherein said engineered meganuclease comprises an amino acid sequence having at least 95% identity to SEQ ID NO:
- 8,
- and wherein said engineered meganuclease binds and produces a cleavage site at a recognition sequence consisting of SEQ ID NO:
- 3 within said human TCR alpha constant region gene;
- and
- (b) introducing into said human T cell a second polynucleotide, wherein said second polynucleotide comprises an exogenous polynucleotide encoding a chimeric antigen receptor or an exogenous TCR, wherein said second polynucleotide is comprised by a recombinant adeno-associated virus (AAV) that is contacted with said human T cell;
- wherein said exogenous polynucleotide is inserted into said human TCR alpha constant region gene at said cleavage site, and wherein said genetically-modified human T cell does not express an endogenous TCR on the cell surface.
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30-69. (canceled)
Dependencies are inferred from the claim text.