Smart CAR devices, DE CAR polypeptides, side CARs and uses thereof
The present invention relates generally to the field of RNA Control Devices and/or destabilizing elements (DE) combined with Chimeric Antigen Receptors (CARs) in eukaryotic cells. The present invention also relates to split CARs (Side-CARs) in eukaryotic cells. More specifically, the present invention relates to DEs, RNA Control Devices, and/or side-CARs combined with Chimeric Antigen Receptors to make small molecule actuatable CAR polypeptides. The present invention also relates to DE-CARs, Smart CARs (Smart=small molecule actuatable RNA trigger), Smart-DE-CARs, and/or Side-CARs for use in the treatment of disease.
1. A nucleic acid comprising: a polynucleotide encoding a RNA control device comprised of a sensor element and a ribozyme element wherein the RNA control device is operably linked to a polynucleotide encoding a chimeric antigen receptor, wherein the chimeric antigen receptor is comprised of an extracellular element, a transmembrane element, and an intracellular element, wherein the ribozyme element acts on an RNA encoding the chimeric antigen receptor and wherein the transmembrane element is between the extracellular element and the intracellular element.
2. The nucleic acid of claim 1 , wherein the polynucleotide encoding the chimeric antigen receptor further comprises a polynucleotide encoding a costimulatory element, wherein the transmembrane element is between the extracellular element and the costimulatory element.
3. The nucleic acid of claim 2 , wherein the costimulatory element is in a domain with the intracellular element.
4. The nucleic acid of claim 2 , wherein the costimulatory element is in a domain separate from the intracellular element.
5. The nucleic acid of claim 1 , further comprising a polynucleotide encoding a hinge element, wherein the hinge element is associated with the transmembrane element.
6. The nucleic acid of claim 1 , further comprising a polynucleotide encoding a hinge element, wherein the hinge element is associated with the extracellular element.
7. A eukaryotic cell comprising a nucleic acid wherein the nucleic acid comprises the polynucleotide of claim 1 .
8. The eukaryotic cell of claim 7 , wherein the eukaryotic cell is a mammalian cell.
9. The eukaryotic cell of claim 8 , wherein the eukaryotic cell is a human cell.
10. The eukaryotic cell of claim 8 , wherein the eukaryotic cell is a murine cell.
11. The eukaryotic cell of claim 7 , wherein the eukaryotic cell is a hematopoietic cell.
12. The eukaryotic cell of claim 11 , wherein the eukaryotic cell is a T-lymphocyte.
13. The eukaryotic cell of claim 11 , wherein the eukaryotic cell is a natural killer cell.