Telomerase reverse transcriptase-based therapies

Abstract

The invention provides compositions and methods useful for the treatment and prevention of conditions associated with short telomere length.

1 .- 12 . (canceled) 
     
     
         13 . A method of treating a condition associated with a disease, the method comprising:
 administering a recombinant viral vector comprising at least a capsid and a nucleic acid comprising a coding sequence for telomerase reverse transcriptase (TERT) to a subject, wherein the condition is associated with pulmonary fibrosis.   
     
     
         14 . The method of  claim 13 , wherein TERT is encoded by a nucleic acid sequence comprising a sequence that is at least 60% identical to the sequence of SEQ ID NO: 1 or SEQ ID NO: 3. 
     
     
         15 . The method of  claim 13 , wherein TERT comprises an amino acid sequence that is at least 60% identical to the amino acid sequence of SEQ ID NO:2 or SEQ ID NO: 4. 
     
     
         16 . The method of  claim 13 , wherein the nucleic acid sequence encoding TERT is operably linked to a regulatory sequence that drives the expression of the coding sequence. 
     
     
         17 . The method of  claim 13 , wherein the vector is a non-integrative vector. 
     
     
         18 . The method of  claim 13 , wherein the vector is an adeno-associated virus-based non-integrative vector. 
     
     
         19 . The method of  claim 13 , wherein the vector is an adeno-associated virus-based vector whose capsid is derived from a serotype 9 adeno-associated virus (AAV9). 
     
     
         20 . The method of  claim 19 , wherein the nucleic acid sequence packaged in the capsid is flanked at both ends by internal terminal repeats of the serotype 2 adeno-associated virus. 
     
     
         21 . The method of  claim 13 , wherein the vector comprises a regulatory sequence which is a constitutive promoter. 
     
     
         22 . The method of  claim 21 , wherein the constitutive promoter is the cytomegalovirus (CMV) promoter. 
     
     
         23 . The method of  claim 13 , wherein the pulmonary fibrosis is characterized by mutations in a gene or genes involved in telomere maintenance.