Telomerase inhibition, telomere shortening, and decreased cell proliferation by cell permeable 2'-O-methoxyethyl oligonucleotides.
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.
Chen
Zhi
Z
Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9041, USA.
Monia
Brett P
BP
Corey
David R
DR
D002455:Cell Division / Q000187:drug effects; D002463:Cell Membrane Permeability; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D009841:Oligonucleotides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D019098:Telomerase / Q000037:antagonists & inhibitors*; D014407:Tumor Cells, Cultured
D004791:Enzyme Inhibitors; D009841:Oligonucleotides; D019098:Telomerase