US 12,448,613 B2
Genetically-modified T cells comprising a modified intron in the T cell receptor alpha gene
Derek Jantz, Durham, NC (US); James Jefferson Smith, Morrisville, NC (US); and Clayton Beard, Durham, NC (US)
Assigned to Precision Biosciences, Inc., Durham, NC (US)
Filed by Precision BioSciences, Inc., Durham, NC (US)
Filed on May 25, 2021, as Appl. No. 17/330,365.
Application 17/330,365 is a continuation of application No. 16/627,052, granted, now 11,053,484, previously published as PCT/US2018/039740, filed on Jun. 27, 2018.
Claims priority of provisional application 62/579,473, filed on Oct. 31, 2017.
Claims priority of provisional application 62/527,845, filed on Jun. 30, 2017.
Prior Publication US 2021/0277373 A1, Sep. 9, 2021
This patent is subject to a terminal disclaimer.
Int. Cl. C12N 9/22 (2006.01); A61K 40/11 (2025.01); A61K 40/31 (2025.01); A61K 40/32 (2025.01); A61K 40/40 (2025.01); C07K 14/725 (2006.01); C12N 5/0783 (2010.01); C12N 15/86 (2006.01); C12N 15/90 (2006.01)
CPC C12N 9/22 (2013.01) [A61K 40/11 (2025.01); A61K 40/31 (2025.01); A61K 40/32 (2025.01); A61K 40/40 (2025.01); C07K 14/7051 (2013.01); C12N 5/0636 (2013.01); C12N 15/86 (2013.01); C12N 15/907 (2013.01); C12N 2750/14143 (2013.01); C12N 2800/60 (2013.01); C12N 2800/80 (2013.01); C12N 2840/20 (2013.01)] 20 Claims
 
1. 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.