Selective induction of apoptosis to treat ocular disease

Abstract

The invention is directed to a method of prophylactically or therapeutically treating choroidal neovascularization, wherein the method comprises directly administering to the eye a therapeutic factor or a nucleic acid sequence that encodes a therapeutic factor, which he expressed to produce the therapeutic factor, to selectively induce apoptosis of endothelial cells associated with neovascularization of the choroid such that choroidal neovascularization is treated prophylactically or therapeutically. The invention also provides a method of prophylactically or therapeutically treating ocular neovascularization, wherein the method comprises directly administering to the eye a nucleic acid sequence encoding a therapeutic factor to promote apoptosis of endothelial cells associated with neovascularization, such that the nucleic acid is expressed thereby producing the therapeutic factor to treat ocular neovascularization prophylactically or therapeutically.

1 . A method of prophylactically or therapeutically treating choroidal neovascularization, wherein the method comprises intravitreously, subretinally, or periocularly injecting an adenoviral vector comprising a nucleic acid sequence encoding pigment epithelium-derived factor operatively linked to a cytomegalovirus (CMV) promoter, which nucleic acid sequence is expressed to produce pigment epithelium-derived factor, to the eye to selectively induce apoptosis of endothelial cells associated with neovascularization of the choroid, such that choroidal neovascularization is treated prophylactically or therapeutically.  
   
   
       2 . The method of  claim 1 , wherein apoptosis induced by pigment epithelium-derived factor in endothelial cells associated with neovascularization of the choroid is at least about 5-times greater than apoptosis induced by pigment epithelium-derived factor in endothelial cells associated with existing vasculature in the eye.  
   
   
       3 . The method of  claim 1 , wherein apoptosis induced by pigment epithelium-derived factor in endothelial cells associated with neovascularization of the choroid is at least about 10-times greater than apoptosis induced by pigment epithelium-derived factor in endothelial cells associated with existing vasculature in the eye.  
   
   
       4 . The method of  claim 3 , wherein apoptosis induced by pigment epithelium-derived factor in endothelial cells associated with neovascularization of the choroid is at least about 50-times greater than apoptosis induced by pigment epithelium-derived factor in endothelial cells associated with existing vasculature in the eye.  
   
   
       5 . The method of  claim 1 , wherein pigment epithelium-derived factor does not affect endothelial cells of existing vasculature.  
   
   
       6 . The method of  claim 3 , wherein the existing vasculature is retinal vasculature.  
   
   
       7 . The method of  claim 1 , wherein the adenoviral vector is replication deficient.  
   
   
       8 . The method of  claim 7 , wherein the adenoviral vector is deficient in one or more gene functions of the E1 region required for viral replication.  
   
   
       9 . The method of  claim 8 , wherein the adenoviral vector is deficient in one or more gene functions of the E4 region required for viral replication.  
   
   
       10 . The method of  claim 7 , wherein the adenoviral vector is deficient in one or more gene functions of the E4 region required for viral replication.  
   
   
       11 . The method of  claim 10 , wherein the adenoviral vector is deficient in all gene functions required for viral replication.  
   
   
       12 . The method of  claim 1 , wherein the adenoviral vector is deficient in one or more gene functions of the E3 region of the adenoviral genome.  
   
   
       13 . The method of  claim 8 , wherein the adenoviral vector is deficient in one or more gene functions of the E3 region of the adenoviral genome.  
   
   
       14 . The method of  claim 9 , wherein the adenoviral vector is deficient in one or more gene functions of the E3 region of the adenoviral genome.  
   
   
       15 . The method of  claim 10 , wherein the adenoviral vector is deficient in one or more gene functions of the E3 region of the adenoviral genome.  
   
   
       16 . The method of  claim 1 , wherein the adenoviral vector is intravitreously injected to the eye.  
   
   
       17 . The method of  claim 16 , wherein the adenoviral vector is deficient in one or more gene functions of the E3 region of the adenoviral genome.  
   
   
       18 . The method of  claim 16 , wherein the adenoviral vector is replication deficient.  
   
   
       19 . The method of  claim 18 , wherein the adenoviral vector is deficient in one or more gene functions of the E1 region required for viral replication.  
   
   
       20 . The method of  claim 19 , wherein the adenoviral vector is deficient in one or more gene functions of the E4 region required for viral replication.  
   
   
       21 . The method of  claim 18 , wherein the adenoviral vector is deficient in one or more gene functions of the E4 region required for viral replication.  
   
   
       22 . The method of  claim 21 , wherein the adenoviral vector is deficient in all gene functions required for viral replication.  
   
   
       23 . The method of  claim 19 , wherein the adenoviral vector is deficient in one or more gene functions of the E3 region of the adenoviral genome.  
   
   
       24 . The method of  claim 20 , wherein the adenoviral vector is deficient in one or more gene functions of the E3 region of the adenoviral genome.  
   
   
       25 . The method of  claim 1 , wherein the adenoviral vector is subretinally injected to the eye.  
   
   
       26 . The method of  claim 25 , wherein the adenoviral vector is deficient in one or more gene functions of the E3 region of the adenoviral genome.  
   
   
       27 . The method of  claim 25 , wherein the adenoviral vector is replication deficient.  
   
   
       28 . The method of  claim 27 , wherein the adenoviral vector is deficient in one or more gene functions of the E1 region required for viral replication.  
   
   
       29 . The method of  claim 28 , wherein the adenoviral vector is deficient in one or more gene functions of the E4 region required for viral replication.  
   
   
       30 . The method of  claim 27 , wherein the adenoviral vector is deficient in one or more gene functions of the E4 region required for viral replication.  
   
   
       31 . The method of  claim 30 , wherein the adenoviral vector is deficient in all gene functions required for viral replication.  
   
   
       32 . The method of  claim 28 , wherein the adenoviral vector is deficient in one or more gene functions of the E3 region of the adenoviral genome.  
   
   
       33 . The method of  claim 29 , wherein the adenoviral vector is deficient in one or more gene functions of the E3 region of the adenoviral genome.  
   
   
       34 . The method of  claim 1 , wherein the adenoviral vector is periocularly injected to the eye.  
   
   
       35 . The method of  claim 34 , wherein the adenoviral vector is deficient in one or more gene functions of the E3 region of the adenoviral genome.  
   
   
       36 . The method of  claim 34 , wherein the adenoviral vector is replication deficient.  
   
   
       37 . The method of  claim 36 , wherein the adenoviral vector is deficient in one or more gene functions of the E1 region required for viral replication.  
   
   
       38 . The method of  claim 37 , wherein the adenoviral vector is deficient in one or more gene functions of the E4 region required for viral replication.  
   
   
       39 . The method of  claim 36 , wherein the adenoviral vector is deficient in one or more gene functions of the E4 region required for viral replication.  
   
   
       40 . The method of  claim 39 , wherein the adenoviral vector is deficient in all gene functions required for viral replication.  
   
   
       41 . The method of  claim 37 , wherein the adenoviral vector is deficient in one or more gene functions of the E3 region of the adenoviral genome.  
   
   
       42 . The method of  claim 38 , wherein the adenoviral vector is deficient in one or more gene functions of the E3 region of the adenoviral genome.