Nucleic acids encoding inactive variants of human telomerase

Abstract

The invention provides compositions and methods related to human telomerase reverse transcriptase (hTRT), the catalytic protein subunit of human telomerase. Catalytically inactive variants comprising deletions or other mutations are provided.

What is claimed as the invention is: 
     
         1 . A nucleic acid that hybridizes to a sequence complementary to SEQ ID NO:1 at 5° C. to 25° C. below T m  in aqueous solution at 1 M NaCl,
 wherein T m  is the melting temperature of double-stranded DNA having the sequence of SEQ ID NO:1 under the same reaction conditions; 
 wherein said nucleic acid encodes at least 500 consecutive amino acids of SEQ ID NO:2, except for one or more deletions that include: 
 a) residues 560-565, 
 b) residues 930-934, 
 c) at least 10 consecutive amino acids from residues 323-450, 
 d) at least 10 consecutive amino acids from residues 637-660, 
 e) at least 10 consecutive amino acids from residues 748-766, 
 f) at least 10 consecutive amino acids from residues 1055-1071, or 
 g) at least 10 consecutive amino acids from residues 1084-1116. 
 
     
     
         2 . A nucleic acid encoding a polypeptide that consists essentially of at least 500 consecutive amino acids of SEQ ID NO:2, except that it contains one or more deletions that include:
 a) residues 560-565,   b) residues 930-934,   c) at least 10 consecutive amino acids from residues 323-450,   d) at least 10 consecutive amino acids from residues 637-660,   e) at least 10 consecutive amino acids from residues 748-766,   f) at least 10 consecutive amino acids from residues 1055-1071, or   g) at least 10 consecutive amino acids from residues 1084-1116.   
     
     
         3 . A nucleic acid encoding a polypeptide that consists essentially of full-length hTRT (SEQ ID NO:2), except for one or more deletions(s) that include:
 a) residues 560-565,   b) residues 930-934,   c) at least 10 consecutive amino acids from residues 323-450,   d) at least 10 consecutive amino acids from residues 637-660,   e) at least 10 consecutive amino acids from residues 748-766,   f) at least 10 consecutive amino acids from residues 1055-1071, or   g) at least 10 consecutive amino acids from residues 1084-1116.   
     
     
         4 . The nucleic acid of  claim 2 , having one or more deletions consisting essentially of residues 560-565, 930-934, 323-450, 637-660, 748-766, 1055-1071, or 1084-1116 of SEQ ID NO:2. 
     
     
         5 . The nucleic acid of  claim 1 , which inhibits telomerase catalytic activity when expressed in a cell expressing human telomerase reverse transcriptase (hTRT) and human telomerase RNA component. 
     
     
         6 . The nucleic acid of  claim 1 , encoding a polypeptide that lacks telomerase catalytic activity, but elicits an antibody response against hTRT when used to immunize a rabbit or mouse. 
     
     
         7 . The nucleic acid of  claim 1 , encoding a polypeptide that binds human telomerase RNA component but lacks processive telomerase activity. 
     
     
         8 . The nucleic acid of  claim 1 , encoding a polypeptide that binds human telomeres but lacks processive telomerase activity. 
     
     
         9 . A nucleic acid according to  claim 1 , which is an expression vector. 
     
     
         10 . A nucleic acid according to  claim 1 , which is an adenovirus expression vector. 
     
     
         11 . A method of inhibiting telomerase catalytic activity in a cell, comprising expressing in the cell a nucleic acid according to  claim 5 . 
     
     
         12 . A method of eliciting an immune response against hTRT in a subject comprising administering to the subject a nucleic acid according to  claim 6 . 
     
     
         13 . The nucleic acid of  claim 3 , which inhibits telomerase catalytic activity when expressed in a cell expressing human telomerase reverse transcriptase (hTRT) and human telomerase RNA component. 
     
     
         14 . The nucleic acid of  claim 3 , encoding a polypeptide that lacks telomerase catalytic activity, but elicits an antibody response against hTRT when used to immunize a rabbit or mouse. 
     
     
         15 . A method of inhibiting telomerase catalytic activity in a cell, comprising expressing in the cell a nucleic acid according to  claim 13 . 
     
     
         16 . A method of eliciting an immune response against hTRT in a subject comprising administering to the subject a nucleic acid according to  claim 14 .