AAV-Mediated Gene Transfer for Retinopathy

Abstract

The present invention relates generally to gene therapy for treating ailments that can affect vision such as retinal degeneration, retinal dystrophy, macular degeneration, macular dystrophy, ischemic retinopathies, and glaucoma. Embodiments include systems and treatments that use AAV-mediated gene therapy or non AAV-mediated DNA, mRNA, or protein therapy to target all retinal cells. An AAV virion can be introduced (e.g., via intravitreal or subretinal injection) into an eye of an individual, or systemically, to express a heterologous gene product such as BMI1 protein (B lymphoma Mo-MLV insertion region 1 homolog).

What is claimed is: 
     
         1 . A pharmaceutical composition for treating a retinopathy in a patient comprising a BMI1 protein encoding viral vector and a pharmaceutically acceptable carrier for the eye. 
     
     
         2 . The pharmaceutical composition of  claim 1 , wherein the viral vector is an AAV virion. 
     
     
         3 . The pharmaceutical composition of  claim 1 , wherein the viral vector particle is AAV type 1, 2, 5, 7, 8, 9 or rh10. 
     
     
         4 . The pharmaceutical composition of  claim 1 , wherein the viral vector particle comprises a nucleic acid sequence encoding a BMI1 protein. 
     
     
         5 . The pharmaceutical composition of  claim 4 , wherein the BMI1 protein has sequence identity in at least about 90% of the aligned sequences. 
     
     
         6 . The pharmaceutical composition of  claim 4 , wherein the BMI1 protein has sequence identity in at least 95% of the aligned sequences. 
     
     
         7 . The pharmaceutical composition of  claim 1 , wherein the pharmaceutical composition is administered into an eye of the patient. 
     
     
         8 . The pharmaceutical composition of  claim 7 , wherein the pharmaceutical composition is administered by an intravitreal, subretinal, sub-internal limiting membrane or suprachoroidal injection into an eye of the patient. 
     
     
         9 . The pharmaceutical composition of  claim 4 , wherein the AAV carries a nucleic acid sequence encoding the BMI1 protein under the control of an inducible or constitutive promoter sequence. 
     
     
         10 . The pharmaceutical composition of  claim 9 , wherein the cell-specific promoter sequence is an inducible promoter or a constitutive promoter. 
     
     
         11 . The pharmaceutical composition of  claim 9 , wherein the promoter is under the control of an enhancer to obtain the desired gene transcription activity. 
     
     
         12 . The pharmaceutical composition of  claim 2 , wherein the composition is in a volume from about 0.1 μL to about 1 mL. 
     
     
         13 . The pharmaceutical composition of  claim 2 , wherein the effective concentration of an AAV in the retina following injection is about 1.5×10 9  vg/mL to about 1.5×10 12  vg/mL, about 1.5×10 9  vg/mL to about 1.5×10 11  vg/mL, about 1.4×10 5  vg/mL. 
     
     
         14 . The pharmaceutical composition of  claim 1 , wherein the pharmaceutical composition is administered in one or more doses to the patient suffering from retinopathy. 
     
     
         15 . The pharmaceutical composition of  claim 1 , wherein the retinopathy is retinal degeneration, retinal vascular disease, retinal dystrophy, macular degeneration, macular dystrophy or glaucoma. 
     
     
         16 . The pharmaceutical composition of  claim 1 , wherein the patient is administered the pharmaceutical composition in a single dose. 
     
     
         17 . The pharmaceutical composition of  claim 1 , wherein the patent is administered the pharmaceutical composition in serial doses. 
     
     
         18 . The pharmaceutical composition of  claim 1 , wherein the patient is administered the pharmaceutical composition at least about once every 5 years to about once every 10 years after the prior dose. 
     
     
         19 . The pharmaceutical composition of  claim 1 , wherein the pharmaceutical composition is administered to the retina of the patient. 
     
     
         20 . The pharmaceutical composition of  claim 2 , wherein the AAV is a chimeric AAV.