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AssigneePrecision BioSciences, Inc.
InventorsDerek Jantz, James Jefferson Smith, Clayton Beard
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The present invention provides a genetically-modified T cell comprising in its genome a modified human T cell receptor alpha gene. The modified T cell receptor alpha gene comprises an exogenous sequence of interest inserted into an intron within the T cell receptor alpha gene that is positioned 5′ upstream of TRAC exon 1. The exogenous sequence of interest can comprise an exogenous splice acceptor site and/or a poly A signal, which disrupts expression of the T cell receptor alpha subunit. The sequence of interest can also include a coding sequence for a polypeptide, such as a chimeric antigen receptor. Additionally, the endogenous splice donor site and the endogenous splice acceptor site flanking the intron are unmodified and/or remain functional. The invention further provides compositions and methods for producing the genetically-modified cell, and populations of the cell, and methods for the treatment of a disease, such as cancer, using such cells.
An isolated genetically-modified human T cell comprising in its genome a modified human T cell receptor alpha gene, wherein said modified human T cell receptor alpha gene comprises an exogenous sequence of interest inserted into an intron within the human T cell receptor alpha gene that is positioned 5′ upstream of the T cell receptor alpha constant region (TRAC) exon 1, and wherein said exogenous sequence of interest comprises an exogenous splice acceptor site or an exogenous splice acceptor site and a poly A signal, and wherein an endogenous splice donor site and an endogenous splice acceptor site flanking said intron are unmodified, and wherein said genetically-modified human T cell does not express an endogenous T cell receptor on the cell surface.
Dependencies are inferred from the claim text.