Tissue selective transgene expression

Abstract

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 .- 13 . (canceled) 
     
     
         14 . A nucleic acid cassette comprising a regulatory element comprising a nucleic acid sequence with at least 95% sequence identity to SEQ ID NO: 30 operably linked to a transgene that results in selective expression of the transgene in parvalbumin (PV) neurons in the CNS over one or more non-PV cells in the CNS. 
     
     
         15 . The nucleic acid cassette of  claim 14 , wherein the transgene comprises a nucleic acid sequence encoding a DNA binding protein. 
     
     
         16 . The nucleic acid cassette of  claim 15 , wherein the DNA binding protein is a transcriptional modulator of an endogenous gene. 
     
     
         17 . The nucleic acid cassette of  claim 15 , wherein the DNA binding protein comprises a zinc finger. 
     
     
         18 . The nucleic acid cassette of  claim 15 , wherein the DNA binding protein is a nuclease-deactivated zinc finger protein. 
     
     
         19 . The nucleic acid cassette of  claim 15 , wherein the DNA binding protein is linked to a transcriptional activator domain. 
     
     
         20 . The nucleic acid cassette of  claim 15 , wherein the DNA binding protein is linked to a transcriptional repressor domain. 
     
     
         21 . The nucleic acid cassette of  claim 15 , wherein the DNA binding protein is a transcriptional activator that modulates an endogenous SCN1A gene. 
     
     
         22 . The nucleic acid cassette of  claim 14 , wherein the nucleic acid cassette is an adeno-associated virus (AAV) vector. 
     
     
         23 . The nucleic acid cassette of  claim 22 , wherein the AAV vector is AAV9 or scAAV9. 
     
     
         24 . The nucleic acid cassette of  claim 15 , wherein the nucleic acid cassette is an adeno-associated virus (AAV) vector. 
     
     
         25 . The nucleic acid cassette of  claim 24 , wherein the AAV vector is AAV9 or scAAV9. 
     
     
         26 . The nucleic acid cassette of  claim 16 , wherein the nucleic acid cassette is an adeno-associated virus (AAV) vector. 
     
     
         27 . The nucleic acid cassette of  claim 26 , wherein the AAV vector is AAV9 or scAAV9. 
     
     
         28 . The nucleic acid cassette of  claim 21 , wherein the nucleic acid cassette is an adeno-associated virus (AAV) vector. 
     
     
         29 . The nucleic acid cassette of  claim 28 , wherein the AAV vector is AAV9. 
     
     
         30 . The nucleic acid cassette of  claim 28 , wherein the AAV vector is scAAV9. 
     
     
         31 . A method for selective expression of a transgene in parvalbumin (PV)-expressing cells, the method comprising: contacting a population of cells comprising PV-expressing cells and non-PV-expressing cells with a nucleic acid cassette comprising a regulatory element comprising a nucleic acid sequence with at least 95% sequence identity to SEQ ID NO: 30 operably linked to the transgene, thereby selectively expressing the transgene in PV-expressing cells. 
     
     
         32 . The method of  claim 31 , wherein the transgene is one or more of SCN1A, SNC2A, SNC8A, SCN1B, SCN2B, KV3.1, KV3.3, and STXBP1. 
     
     
         33 . The method of  claim 31 , wherein the regulatory element is less than 2.5 kb in size.