Promoters exhibiting endothelial cell specificity and methods of using same for regulation of angiogenesis

Abstract

Isolated polynucleotide sequences exhibiting endothelial cell specific promoter activity, novel cis regulatory elements and methods of use thereof enabling treatment of diseases characterized by aberrant neovascularization or cell growth are disclosed.

1 . A nucleic acid construct comprising an isolated polynucleotide which comprises a conditionally replicating adenovirus transcriptionally linked to a pre-proendothelin-1 promoter, wherein said promoter selectively directs transcription of said adenovirus in angiogenic endothelial cells, and wherein said nucleic acid construct is devoid of non-viral heterologous sequences encoding pro- or anti-angiogenic agents. 
     
     
         2 . The nucleic acid construct of  claim 1 , wherein said promoter is a PPE-1-3× promoter. 
     
     
         3 . The nucleic acid construct of  claim 1 , wherein said promoter comprises at least one copy of the sequence set forth in SEQ ID NO:1. 
     
     
         4 . The nucleic acid construct of  claim 1 , wherein said isolated polynucleotide further comprises a polynucleotide sequence as set forth in SEQ ID NO: 7. 
     
     
         5 . The nucleic acid construct of  claim 1 , wherein said conditionally replicating adenovirus comprises an adenoviral E1 region. 
     
     
         6 . The nucleic acid construct of  claim 1 , wherein said conditionally replicating adenovirus vector is an adenovirus-5 vector. 
     
     
         7 . The nucleic acid construct of  claim 1 , which construct further comprises at least one hypoxia responsive element having a sequence as set forth in SEQ ID NO:5. 
     
     
         8 . The nucleic acid construct of  claim 1 , wherein said nucleic acid construct is further devoid of reporter gene sequences.