Methods and Compositions for Treatment of Disorders and Diseases Involving RDH12

Abstract

Codon optimized nucleic acid sequences for RDH12 are provided, as well as recombinant viral vectors, such as AAV, expression cassettes, proviral plasmids or other plasmids containing the codon optimized sequence for functional RDH12. Recombinant vectors are provided that express the codon optimized, functional RDH12. Compositions containing these codon optimized sequences are useful in methods for treating, retarding or halting certain blinding diseases resulting from the absence, deficiency or inappropriate expression of RDH12. Other compositions and methods are providing for correcting a non-functional, defective or inadequately expressed native RDH12.

1 . (canceled) 
     
     
         2 . A recombinant adeno-associated virus (rAAV) comprising an AAV capsid protein and a nucleic acid comprising a nucleotide sequence at least 90% identical to SEQ ID NO: 5. 
     
     
         3 . The rAAV of  claim 2 , wherein the nucleotide sequence is at least 95% identical to SEQ ID NO: 5. 
     
     
         4 . The rAAV of  claim 2 , wherein the nucleotide sequence is codon optimized for expression in a human cell. 
     
     
         5 . The rAAV of  claim 2 , wherein the nucleotide sequence is operatively associated with expression control sequences that can direct expression of the nucleotide sequence in a host cell. 
     
     
         6 . An rAAV expression cassette comprising the nucleotide sequence of  claim 2 , a 5′ AAV inverted terminal repeat (ITR), a 3′ AAV ITR, and expression control sequences that can direct expression of the nucleotide sequence in a host cell. 
     
     
         7 . The rAAV expression cassette of  claim 6 , wherein the nucleotide sequence is at least 95% identical to SEQ ID NO: 5. 
     
     
         8 . A plasmid comprising the expression cassette of  claim 6 . 
     
     
         9 . The rAAV of  claim 5 , wherein the host cell is a human cell. 
     
     
         10 . The rAAV of  claim 5 , wherein the host cell is a photoreceptor cell. 
     
     
         11 . The rAAV of  claim 5 , wherein the expression control sequences comprise a rhodopsin kinase promoter sequence. 
     
     
         12 . The rAAV of  claim 5 , wherein the expression control sequences comprise a BGH polyadenylation sequence. 
     
     
         13 . The rAAV of  claim 2 , wherein the AAV capsid protein is from an AAV8 capsid, or variant thereof, an AAV7 capsid, or variant thereof, an AAV5 capsid, or variant thereof, or an AAV2 capsid or variant thereof. 
     
     
         14 . The rAAV of  claim 2 , wherein the AAV capsid protein is from an AAV8 capsid. 
     
     
         15 . A host cell comprising the rAAV of  claim 2 . 
     
     
         16 . A composition comprising the rAAV of  claim 2  and a carrier or excipient suitable for delivery to a plurality of ocular cells of a subject. 
     
     
         17 . The composition of  claim 16 , wherein the composition is delivered to the host cell via a lipid delivery vehicle. 
     
     
         18 . The composition of  claim 17 , wherein the lipid delivery vehicle is a liposome. 
     
     
         19 . An rAAV comprising an AAV8 capsid and an expression cassette comprising:
 a) a 5′ AAV ITR;   b) a rhodopsin kinase promoter;   c) a nucleotide sequence at least 90% identical to SEQ ID NO: 5; and   d) a 3′AAV ITR.   
     
     
         20 . The rAAV of  claim 19 , wherein the nucleotide sequence is at least 95% identical to SEQ ID NO: 5. 
     
     
         21 . A composition comprising the rAAV of  claim 19 , and a pharmaceutically acceptable excipient. 
     
     
         22 . The composition of  claim 21 , wherein the pharmaceutically acceptable excipient is a carrier or excipient suitable for delivery to a plurality of ocular cells of a subject. 
     
     
         23 . The composition of  claim 21 , wherein the composition is delivered to the host cell via a lipid delivery vehicle. 
     
     
         24 . The composition of  claim 23 , wherein the lipid delivery vehicle is a liposome. 
     
     
         25 . The composition of  claim 22 , wherein the subject is a human.