Genomic engineering of pluripotent cells
AssigneeFate Therapeutics, Inc.
InventorsBahram Valamehr, Ramzey Abujarour, Tom Tong Lee, Weijie Lan, Raedun Clarke, Ryan Bjordahl
Life of this patent
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Abstract
Provided are methods and compositions for obtaining genome-engineered iPSCs, and derivative cells with stable and functional genome editing at selected sites. Also provided are cell populations or clonal cell lines derived from genome-engineered iPSCs, which comprise targeted integration of one or more exogenous polynucleotides, and/or in/dels in one or more selected endogenous genes.
Claims24
A cell or population thereof, wherein (i) the cell is an induced pluripotent stem cell (iPSC), a clonal iPSC, or an iPSC line cell;
- and (ii) the cell comprises:
- (a) one or more exogenous polynucleotides at an endogenous T cell receptor (TCR) alpha locus, wherein at least one of the one or more exogenous polynucleotides encodes a chimeric antigen receptor (CAR), and wherein the one or more exogenous polynucleotides encoding the CAR is expressed under the control of an endogenous promoter of said TCR alpha locus;
- and (b) introduced or increased expression of CD16, wherein the CD16 is a high affinity non-cleavable CD16 (hnCD16).
A cell or population thereof, wherein (i) the cell is an induced pluripotent stem cell (iPSC), a clonal iPSC, or an iPSC line cell;
- (ii) the cell comprises a polynucleotide encoding at least one chimeric antigen receptor (CAR) introduced into a T cell receptor (TCR) alpha locus;
- (iii) an endogenous TCR alpha gene is knocked out;
- and (iv) expression of the polynucleotide encoding at least one CAR is under control of an endogenous TCR promoter of the TCR alpha locus.
A cell or population thereof, wherein (i) the cell is an induced pluripotent stem cell (iPSC), a clonal iPSC, or an iPSC line cell;
- and (ii) the cell comprises:
- (a) one or more exogenous polynucleotides present in an endogenous T cell receptor (TCR) alpha locus, wherein the at least one or more exogenous polynucleotides encodes a chimeric antigen receptor (CAR), and the exogenous polynucleotide encoding the CAR is expressed under the control of an endogenous promoter of said TCR alpha locus;
- and (b) deletion or reduced expression in at least one of B2M, TAP1, TAP2, Tapasin, NLRC5, PD1, LAG3, TIM3, RFXANK, CIITA, RFX5, RFXAP and any gene in the chromosome 6p21 region;
- and/or introduced or increased expression in at least one of HLA-E, HLA-G, CD16, 41BBL, CD3, CD4, CD8, CD47, CD113, CD131, CD137, CD80, PDL1, A2aR, Fc receptor, an engager, and a surface triggering receptor for coupling with bi-, multi-specific or universal engagers.
Dependencies are inferred from the claim text.