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 . (Cancel).  
     
     
         28 . A method of producing an antibody of interest, comprising the steps of: 
 enhancing telomerase expression in an antibody forming cell that produces said antibody of interest by administering to said cell an effective amount of an agent that inhibits Site C TERT transcription repression; and    growing the resultant immortalized antibody producing cell and its progeny under conditions which allow the cells to produce said antibody of interest.    
     
     
         29 . The method according to  claim 28 , wherein said agent modulates binding of a factor to a Site C repressor binding site.  
     
     
         30 . The method according to  claim 29 , wherein said Site C repressor binding site ranges in length from about 5 to about 100 bases.  
     
     
         31 . The method according to  claim 30 , wherein said Site C repressor binding site ranges in length from about 5 to 45 bases.  
     
     
         32 . The method according to  claim 29 , wherein said Site C repressor binding site 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 or its complementary sequence.  
     
     
         33 . The method according to  claim 28 , wherein said agent comprises a nucleic acid.  
     
     
         34 . The method according to  claim 28 , wherein said agent comprises a peptide or a protein.  
     
     
         35 . The method according to  claim 28 , wherein said agent is a small molecule.  
     
     
         36 . The method according to  claim 28 , wherein said antibody forming cell is a B cell.  
     
     
         37 . The method according to  claim 36 , wherein said method further comprises isolating said B cell from a mammal  
     
     
         38 . A method of producing a mammalian antibody, comprising the steps of: 
 isolating a B cell from a mammal, which B cell or its progeny cell is characterized by producing an antibody of interest;    enhancing telomerase expression in said B cell by administering to said cell an effective amount of a nucleic acid agent that inhibits Site C TERT transcription repression; and    growing the immortalized B cell and its progeny under conditions which allow the cells to produce the antibody of interest.    
     
     
         39 . The method according to  claim 38 , wherein said nucleic acid agent modulates binding of a factor to a Site C repressor binding site.  
     
     
         40 . The method according to  claim 39 , wherein said Site C repressor binding site ranges in length from about 5 to about 100 bases.  
     
     
         41 . The method according to  claim 40 , wherein said Site C repressor binding site ranges in length from about 5 to 45 bases.  
     
     
         42 . The method according to  claim 39 , wherein said Site C repressor binding site 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 or its complementary sequence.  
     
     
         43 . The method according to  claim 38 , wherein said agent is a double stranded DNA decoy sequence comprising a Site C repressor binding site.  
     
     
         44 . The method according to  claim 43 , wherein said decoy comprises a sequence selected from the group consisting of SEQ ID NOs: 01 to 04.  
     
     
         45 . The method according to  claim 43 , wherein said decoy ranges in length from about 10 to about 50 bases.  
     
     
         46 . A cell produced according to the method of  claim 28 .  
     
     
         47 . A cell produced according to the method of  claim 38.