Methods and compositions for modulating telomerase reverse transcriptase (TERT) expression

Abstract

Methods and compositions are provided for modulating, and generally upregulating, the expression of telomerase reverse transcriptase (TERT) by blocking repression of TERT transcription, e.g., by inhibiting binding of repressor factor to a Site C repressor binding site located in the TERT minimal promoter. The subject methods and compositions find use in a variety of different applications, including the immortalization of cells, the production of reagents for use in life science research, therapeutic applications; therapeutic agent screening applications; and the like. In further describing the subject invention, the methods and compositions of the invention are described first in greater detail, followed by a review of the various applications in which the subject invention finds use.

1 - 27 . (canceled)  
     
     
         28 . A nucleic acid present in other than its natural environment, wherein said nucleic acid has a nucleotide sequence that is the same as or substantially identical to the Site C repressor binding site and said nucleic acid does not include the full minimal TERT promoter sequence.  
     
     
         29 . The nucleic acid according to  claim 28 , wherein said nucleic acid comprises no more than about 90 number % of the full sequence of the hTERT minimal promoter.  
     
     
         30 . The nucleic acid according to  claim 29 , wherein said nucleic acid comprises no more than about 50 number % of the full sequence of the minimal hTERT promoter sequence.  
     
     
         31 . The nucleic acid according  claim 28 , wherein said nucleic acid has a length ranging from about 5 to about 5000 bases.  
     
     
         32 . The nucleic acid according to  claim 31 , wherein said nucleic acid has a length ranging from about 10 to about 2500 bases.  
     
     
         33 . The nucleic acid according to  claim 32 , wherein said nucleic acid has a length ranging from about 10 to about 500 bases.  
     
     
         34 . The nucleic acid according to  claim 33 , wherein said nucleic acid has a length ranging from about 10 to about 50 bases.  
     
     
         35 . The nucleic acid according to  claim 28 , wherein said nucleic acid is isolated.  
     
     
         36 . The nucleic acid according to  claim 28 , wherein said nucleic acid has a sequence that is substantially the same as or identical to a sequence found in a sequence selected from the group consisting of SEQ ID NOs:01 to 04.  
     
     
         37 . An isolated nucleic acid or mimetic thereof that hybridizes under stringent conditions to the nucleic acid according to  claim 28  or its complementary sequence, wherein said isolated nucleic acid does not include the full TERT minimal promoter sequence.  
     
     
         38 . A construct comprising a nucleic acid according to  claim 28 .  
     
     
         39 . The construct according to  claim 38 , wherein said construct comprises a TERT promoter.  
     
     
         40 . The construct according to  claim 39 , wherein said construct is an expression cassette.  
     
     
         41 . A double stranded DNA decoy sequence comprising a Site C repressor binding site.  
     
     
         42 . The decoy according to  claim 41 , wherein said decoy comprises a sequence selected from the group consisting of SEQ ID NOs: 01 to 04.  
     
     
         43 . The decoy according to  claim 42 , wherein said decoy ranges in length from about 10 to about 50 bases.  
     
     
         44 . A method comprising administering to cells a decoy according to  claim 41 .  
     
     
         45 . A mammalian cell comprising a telomerase gene modified by deletion of any of the nucleotides found in a Site C repressor.  
     
     
         46 . The cell according to  claim 45 , wherein said deletion is any of nucleotides found in a sequence selected from the group consisting of SEQ ID NOs: 01 to 04.