Genetically-modified immune cells comprising a microRNA-adapted shRNA (shRNAmiR)
AssigneePrecision BioSciences, Inc.
InventorsAaron Martin, Jon E. Chatterton, Michelle Brenda Pires
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Abstract
The present invention encompasses genetically-modified immune cells (and populations thereof) expressing a microRNA-adapted shRNA (shRNAmiR) that reduces the expression of a target endogenous protein. Methods for reducing the expression of an endogenous protein in an immune cell are also provided wherein the method comprises introducing a shRNAmiR that targets the endogenous protein. Using shRNAmiRs for knocking down the expression of a target protein allows for stable knockdown of expression of endogenous proteins in immune cells.
Claims8
A genetically-modified human T cell comprising in its genome a cassette comprising:
- (a) a promoter;
- (b) a nucleic acid sequence encoding a chimeric antigen receptor (CAR) or an exogenous T cell receptor (TCR);
- (c) a nucleic acid sequence encoding a deoxycytidine kinase (DCK)-targeting microRNA-adapted shRNA (shRNAmiR) comprising SEQ ID NO:
- 86;
- and
- (d) a termination signal;
- wherein said nucleic acid sequence encoding said CAR or said exogenous TCR and said nucleic acid sequence encoding said shRNAmiR are operably linked to said promoter,
- and wherein said cassette is positioned within a T cell receptor (TCR) alpha constant region gene.
A genetically-modified human T cell comprising in its genome a cassette comprising:
- (a) a first promoter;
- (b) a nucleic acid sequence encoding a CAR or an exogenous TCR, wherein said nucleic acid sequence encoding said CAR or said exogenous TCR is operably linked to said first promoter;
- (c) a second promoter;
- and
- (d) a nucleic acid sequence encoding a deoxycytidine kinase (DCK)-targeting microRNA-adapted shRNA (shRNAmiR) comprising SEQ ID NO:
- 86, wherein said nucleic acid sequence encoding said DCK-targeting shRNAmiR is operably linked to said second promoter;
- wherein said cassette is positioned within a T cell receptor (TCR) alpha constant region gene.
Dependencies are inferred from the claim text.