ISOLATED POLYNUCLEOTIDES AND NUCLEIC ACID CONSTRUCTS FOR DIRECTING EXPRESSION OF A GENE-OF-INTEREST IN CELLS

摘要

Isolated polynucleotides comprising at least 14 nucleotides of SEQ ID NO:6 of a pre-proendothelin promoter which comprise at least 2 consecutive sequences being positioned next to at least one nucleotide position selected from the group consisting of at least one nucleotide of SEQ ID NO:46, 47, 52, 49, 50, 53 and 54, which is mutated as compared to SEQ ID NO:6 such that when the isolated polynucleotide is integrated into the PPE-1 promoter and placed upstream of a luciferase coding sequence the expression level of the luciferase coding sequence is upregulated or downregulated as compared to when SEQ ID NO:6 is similarly integrated into the PPE-1 promoter and placed upstream of the luciferase coding sequence. Also provided are nucleic acid constructs comprising same, methods of using same and pharmaceutical compositions comprising same for increasing or decreasing expression of a polynucleotide of interest in endothelial and non-endothelial cells.