Tissue selective transgene expression
Provided herein are compositions and methods for selective expression of a transgene. Compositions and methods for selective expression of a transgene comprise one or more human regulatory elements, which, when operably linked to a transgene, can facilitate selective expression of a transgene (e.g., cell-type selective expression) in a target cell as compared to at least one or more non-target cells.
1. A nucleic acid cassette comprising a regulatory element comprising SEQ ID NO: 30 operably linked to a transgene.
2. The nucleic acid cassette of claim 1 , wherein the transgene comprises a nucleic acid sequence encoding a DNA binding protein.
3. The nucleic acid cassette of claim 2 , wherein the DNA binding protein is a transcriptional modulator of an endogenous gene.
4. The nucleic acid cassette of claim 2 , wherein the DNA binding protein comprises a zinc finger.
5. The nucleic acid cassette of claim 2 , wherein the DNA binding protein is a nuclease-deactivated zinc finger protein.
6. The nucleic acid cassette of claim 2 , wherein the DNA binding protein is linked to a transcriptional activator domain.
7. The nucleic acid cassette of claim 2 , wherein the DNA binding protein is linked to a transcriptional repressor domain.
8. The nucleic acid cassette of claim 2 , wherein the DNA binding protein is a transcriptional activator that modulates an endogenous SCN1A gene.
9. The nucleic acid cassette of claim 1 , wherein the nucleic acid cassette is an adeno-associated virus (AAV) vector.
10. The nucleic acid cassette of claim 9 , wherein the AAV vector is AAV9 or scAAV9.
11. The nucleic acid cassette of claim 8 , wherein the nucleic acid cassette is an adeno-associated virus (AAV) vector.
12. The nucleic acid cassette of claim 11 , wherein the AAV vector is AAV9.
13. The nucleic acid cassette of claim 11 , wherein the AAV vector is scAAV9.