Promoters, expression cassettes, vectors, kits, and methods for the treatment of achromatopsia and other diseases

Abstract

The present invention provides isolated promoters, transgene expression cassettes, vectors, kits, and methods for treatment of genetic diseases that affect the cone cells of the retina.

1 . A nucleic acid comprising a cone cell specific promoter PR 1.7. 
     
     
         2 . The nucleic acid of  claim 1 , wherein the promoter PR 1.7 comprises a nucleic acid sequence that is at least 90% identical to SEQ ID NO: 3. 
     
     
         3 . The nucleic acid of  claim 1 , wherein the promoter PR 1.7 comprises a nucleic acid sequence that is at least 95% identical to SEQ ID NO: 3. 
     
     
         4 . The nucleic acid of  claim 1 , wherein the promoter PR 1.7 comprises a nucleic acid sequence that is at least 99% identical to SEQ ID NO: 3. 
     
     
         5 . The nucleic acid of  claim 1 , wherein the promoter PR 1.7 consists of SEQ ID NO: 3. 
     
     
         6 . The nucleic acid of  claim 1 , wherein the promoter is capable of promoting CNGB3 expression in S-cone cells, M-cone cells, and L-cone cells. 
     
     
         7 . The nucleic acid of  claim 1 , wherein the promoter is capable of promoting CNGA3 expression in S-cone cells, M-cone cells, and L-cone cells. 
     
     
         8 . The nucleic acid of  claim 1 , wherein the promoter is capable of promoting GNAT2 expression in S-cone cells, M-cone cells, and L-cone cells. 
     
     
         9 . A recombinant adeno-associated (rAAV) expression vector comprising a target nucleic acid sequence operably linked to the nucleic acid of  claim 1 . 
     
     
         10 . The expression vector of  claim 9 , wherein the target nucleic acid sequence encodes a cyclic nucleotide-gated channel subunit B (CNGB3) polypeptide. 
     
     
         11 . The expression vector of  claim 10 , wherein the target nucleic acid sequence encodes a cyclic nucleotide-gated channel subunit A (CNGA3) polypeptide. 
     
     
         12 . The expression vector of  claim 11 , wherein the CNGA3 is mouse CNGA3. 
     
     
         13 . The expression vector of  claim 11 , wherein the CNGA3 is rat CNGA3. 
     
     
         14 . The expression vector of  claim 11 , wherein the CNGA3 is human CNGA3. 
     
     
         15 . The expression vector of  claim 10 , wherein the target nucleic acid sequence encodes a Guanine nucleotide-binding protein G(t) subunit alpha-2 (GNAT-2) polypeptide. 
     
     
         16 . The expression vector of  claim 15 , wherein the GNAT-2 is mouse GNAT-2. 
     
     
         17 . The expression vector of  claim 15 , wherein the GNAT-2 is rat GNAT-2. 
     
     
         18 . The expression vector of  claim 15 , wherein the GNAT-2 is human GNAT-2. 
     
     
         19 . A mammalian cell comprising the expression vector of  claim 10 . 
     
     
         20 . A transgene expression cassette comprising:
 (a) the nucleic acid of  claim 1 ;   (b) a nucleic acid selected from the group consisting of a CNGB3 nucleic acid, a CNGA3 nucleic acid, and a GNAT2 nucleic acid; and   (c) minimal regulatory elements.