Viral vector encoding pigment epithelium-derived factor

Abstract

The present invention provides a viral vector comprising a nucleic acid sequence encoding pigment epithelium-derived factor (PEDF) or a therapeutic fragment thereof. The nucleic acid sequence is operably linked to regulatory sequences necessary for expression of PEDF or a therapeutic fragment thereof. Preferably, the viral vector is an adenoviral vector or an adeno-associated viral vector. Also preferably, the viral vector further comprises one or more additional nucleic acid sequences encoding therapeutic substances other than PEDF.

1 . An adeno-associated viral vector comprising a nucleic acid sequence encoding pigment epithelium-derived factor (PEDF) or a therapeutic fragment thereof, wherein the nucleic acid sequence is operably linked to regulatory sequences necessary for expression of PEDF or a therapeutic fragment thereof.  
     
     
         2 . The viral vector of  claim 1 , wherein the adeno-associated viral vector comprises a genome that is deficient in the rep and cap genes.  
     
     
         3 . The viral vector of  claim 1 , wherein the adeno-associated viral vector requires co-infection with a helper virus for replication.  
     
     
         4 . The viral vector of  claim 3 , wherein the helper virus is an adenovirus or a herpes virus.  
     
     
         5 . The viral vector of  claim 1 , wherein the regulatory sequences comprise a promoter selected from the group consisting of a CMV promoter, an RSV promoter, an adeno-associated virus p5 promoter, a Lap2 promoter, an EF1α promoter, and a β-actin promoter.  
     
     
         6 . The viral vector of  claim 5 , wherein the regulatory sequences comprise an RSV promoter.  
     
     
         7 . The viral vector of  claim 1 , wherein the regulatory sequences comprise an inducible promoter.  
     
     
         8 . The viral vector of  claim 1 , further comprising one or more additional nucleic acid sequences encoding therapeutic substances other than PEDF or a therapeutic fragment thereof.  
     
     
         9 . The viral vector of  claim 8 , wherein one or more additional nucleic acid sequences encodes ciliary neurotrophic factor (CNTF).  
     
     
         10 . The viral vector of  claim 8 , wherein one or more additional nucleic acid sequences encodes an atonal-associated peptide.  
     
     
         11 . The viral vector of  claim 8 , wherein one or more additional nucleic acid sequences encodes an anti-angiogenic substance.  
     
     
         12 . The viral vector of  claim 11 , wherein the anti-angiogenic substance is a soluble receptor specific for an angiogenic factor.  
     
     
         13 . The viral vector of  claim 12 , wherein the soluble receptor specific for an angiogenic factor is a soluble VEGF-R1 receptor.  
     
     
         14 . The viral vector of  claim 8 , wherein the therapeutic substances other than PEDF or a therapeutic fragment thereof are linked to an endoplasmic reticulum localization signal peptide.