Method to inhibit cell growth using oligonucleotides

Abstract

Described are methods for treating hyperproliferative disorders, including cancers, by administering to the affected mammal (e.g., human) an effective amount of a composition comprising one or more oligonucleotides which share at least 33% but less than 100% nucleotide sequence identity with the human telomere overhang repeat. Methods of treatment or prevention of hyperproliferative diseases or pre-cancerous conditions affecting epithelial cells, such as psoriasis, atopic dermatitis, or hyperproliferative diseases of other epithelia and methods for reducing photoaging, or oxidative stress or for prophylaxis against or reduction in the likelihood of the development of skin cancer, are also disclosed. The compositions and methods are also useful to treating other cancers.

1 . A method of treating a hyperproliferative disorder in a mammal the method comprising administering to the mammal an effective amount of a composition comprising one or more oligonucleotides, said oligonucleotide having between 2 and 200 bases and having at least 33% but less than 100% identity with the sequence (TTAGGG) n , and optionally having a 5′ phosphate, and when said oligonucleotide comprises the sequence 5′-RRRGGG-3′ (R=any nucleotide) said oligonucleotide has a guanine content of 50% or less. 
     
     
         2 . The method of  claim 1  wherein said oligonucleotide lacks cytosine. 
     
     
         3 . A method for inhibiting growth of cancer cells in a human comprising administering to the human an effective amount of a composition comprising one or more oligonucleotides, said oligonucleotide having between 2 and 200 bases and having at least 33% but less than 100% identity with the sequence (TTAGGG) n , and optionally having a 5′ phosphate, and when said oligonucleotide comprises the sequence 5′-RRRGGG-3′ (R=any nucleotide) said oligonucleotide has a guanine content of 50% or less. 
     
     
         4 . The method of  claim 3  wherein said oligonucleotide lacks cytosine. 
     
     
         5 . A method of promoting differentiation of malignant cells in a mammal comprising one or more oligonucleotides, said oligonucleotide having between 2 and 200 bases and having at least 33% but less than 100% identity with the sequence (TTAGGG) n , and optionally having a 5′ phosphate, and when said oligonucleotide comprises the sequence 5′-RRRGGG-3′ (R=any nucleotide) said oligonucleotide has a guanine content of 50% or less. 
     
     
         6 . The method of  claim 5  wherein said oligonucleotide lacks cytosine. 
     
     
         7 . A method of inducing apoptosis in a cancer cell said method comprising administering to the mammal one or more oligonucleotides, said oligonucleotide having between 2 and 200 bases and having at least 33% but less than 100% identity with the sequence (TTAGGG) n , and optionally having a 5′ phosphate, and when said oligonucleotide comprises the sequence 5′-RRRGGG-3′ (R=any nucleotide) said oligonucleotide has a guanine content of 50% or less. 
     
     
         8 . The method of  claim 7  wherein said oligonucleotide lacks cytosine. 
     
     
         9 . The method for reducing the occurrence of skin cancer in a human the method comprising one or more oligonucleotides, said oligonucleotide having between 2 and 200 bases and having at least 33% but less than 100% identity with the sequence (TTAGGG) n , and optionally having a 5′ phosphate, and when said oligonucleotide comprises the sequence 5′-RRRGGG-3′ (R=any nucleotide) said oligonucleotide has a guanine content of 50% or less. 
     
     
         10 . The method of  claim 9  wherein said oligonucleotide lacks cytosine.