Modulation of telomere length by oligonucleotides having a G-core sequence

Abstract

Modified oligonucleotides having a GGG motif sequence and a sufficient number of flanking nucleotides to modulate the telomere length of a chromosome are provided. Methods of modulating telomere length of a mammalian chromosome in vitro and in vivo are also provided, as are methods for inhibiting the division of a malignant mammalian cell and for modulating the effects of cellular aging.

1 . A method of modulating telomere length of a mammalian chromosome comprising contacting a mammalian chromosome with a chemically modified oligonucleotide having no more than 27 nucleic acid base units, said oligonucleotide having the sequence (N X G 3-4 ) Q N X  wherein each X is independently 1 to 8 and Q is 1 to 6, wherein said oligonucleotide modulates mammalian telomere length.  
     
     
         2 . The method of  claim 1  which is carried out in vitro.  
     
     
         3 . The method of  claim 1  which is carried out in vivo.  
     
     
         4 . The method of  claim 1  wherein the oligonucleotide chemical modifications are selected from the group consisting of a modified internucleoside linkage, a modified sugar and a modified base.  
     
     
         5 . A method for inhibiting the division of a malignant mammalian cell comprising contacting said malignant mammalian cell with a chemically modified oligonucleotide having no more than 27 nucleic acid base units, said oligonucleotide having the sequence (N X G 3-4 ) Q N X  wherein each X is independently 1 to 8 and Q is 1 to 6, wherein said oligonucleotide modulates mammalian telomere length.  
     
     
         6 . The method of  claim 5  which is carried out in vitro.  
     
     
         7 . The method of  claim 5  which is carried out in vivo.  
     
     
         8 . The method of  claim 5  wherein the oligonucleotide chemical modifications are selected from the group consisting of a modified internucleoside linkage, a modified sugar and a modified base.  
     
     
         9 . A method for inhibiting the division of a malignant mammalian cell comprising contacting said malignant mammalian cell with a chemically modified oligonucleotide having no more than 27 nucleic acid base units, said oligonucleotide comprising the sequence (N x G 3-4 ) Q N x  wherein X is 1 to 8 and Q is 1 to 6, wherein said oligonucleotide modulates mammalian telomere length.  
     
     
         10 . The method of  claim 9  which is carried out in vitro.  
     
     
         11 . The method of  claim 9  which is carried out in vivo.  
     
     
         12 . The method of  claim 9  wherein the oligonucleotide chemical modifications are selected from the group consisting of a modified internucleoside linkage, a modified sugar and a modified base.