Telomerase inhibition, telomere shortening, and decreased cell proliferation by cell permeable 2'-O-methoxyethyl oligonucleotides

Abstract

Telomerase is an attractive target for chemotherapy. Testing this hypothesis will require potent inhibitors with favorable pharmacokinetic properties. We report that 2'-methoxyethyl oligonucleotides complementary to the telomerase RNA component diffuse across cell membranes without the need for cationic carrier lipid, inhibit telomerase, and cause telomeres to shorten. The ability of antitelomerase oligomers to enter cells without the need to add lipid will simplify preclinical studies and may suggest advantages for clinical use.