Viral vectors comprising rdh12 coding regions and methods of treating retinal dystrophies

Abstract

Provided are materials, methods and uses for treating an ophthalmological condition such as Leber Congenital Amaurosis by administering an effective amount of an adeno-associated virus AAV2, serotype 5 (AAV 2/5) or AAV-5 comprising an expressible coding region for human RDH12.

1 . A method of treating a human subject who has an ophthalmological condition due to one or more loss-of-function mutations in the gene encoding the Retinol Dehydrogenase 12 (RDH12) protein, the method comprising administering to at least one eye of the subject an adeno-associated viral vector comprising a nucleic acid, wherein the nucleic acid comprises human RDH12 DNA and wherein the human RDH12 DNA encodes a protein that is at least 70%, 80%, 90%, 95%, or 99% identical to the full length of SEQ ID NO:2. 
     
     
         2 . The method of  claim 1  wherein the ophthalmological condition is Leber Congenital Amaurosis (LCA). 
     
     
         3 . The method of  claim 1  wherein the RDH12 DNA is under the expression control of a human rhodopsin kinase 1 (hGRK1) promoter. 
     
     
         4 . The method of  claim 3  wherein the hGRK1 promoter comprises SEQ ID NO:3. 
     
     
         5 . The method of  claim 1  wherein the adeno-associated viral vector is AAV-2, serotype-5 (AAV2/5) or AAV-5. 
     
     
         6 - 7 . (canceled) 
     
     
         8 . The method of  claim 1  wherein the nucleic acid is administered into the subretinal space. 
     
     
         9 . The method of  claim 8 , wherein a micro injection cannula is inserted into the subretinal space. 
     
     
         10 . A nucleic acid encoding a human RDH12 DNA, wherein the human RDH12 DNA encodes a protein that is at least 70%, 80%, 90%, 95%, or 99% identical to the full length of SEQ ID NO:2, wherein the RDH12 DNA is under the control of a human rhodopsin kinase 1 (hGRK1) promoter. 
     
     
         11 . The nucleic acid of  claim 10 , wherein the hGRK1 promoter comprises SEQ ID NO:3. 
     
     
         12 . The nucleic acid of  claim 10 , wherein the human RDH12 DNA encodes a protein comprising SEQ ID NO:2. 
     
     
         13 . The nucleic acid of  claim 10 , wherein the human RDH12 DNA is at least 60% or 70% identical to the full length of SEQ ID NO: 1. 
     
     
         14 . The nucleic acid of  claim 10 , for use in treating a human subject who has an ophthalmological condition due to one or more loss-of-function mutations in the gene encoding the Retinol Dehydrogenase 12 (RDH12) protein. 
     
     
         15 . The nucleic acid of  claim 14  wherein the ophthalmological condition is Leber Congenital Amaurosis (LCA). 
     
     
         16 . A viral vector comprising the nucleic acid of  claim 10 . 
     
     
         17 . The viral vector of  claim 16 , which is an adeno-associated viral vector. 
     
     
         18 . The viral vector of  claim 17 , wherein the adeno-associated viral vector is AAV-2, serotype-5 (AAV2/5) or AAV-5. 
     
     
         19 . The viral vector of  claim 16 , for use in treating a human subject who has an ophthalmological condition due to one or more loss-of-function mutations in the gene encoding the Retinol Dehydrogenase 12 (RDH12) protein. 
     
     
         20 . The viral vector of  claim 19  wherein the ophthalmological condition is Leber Congenital Amaurosis (LCA). 
     
     
         21 . An isolated host cell comprising the the nucleic acid of  claim 10 . 
     
     
         22 . The isolated host cell of  claim 21 , wherein the cell expresses a human RDH12 protein.