There is an increasing interest in using selected antisense oligodeoxynucleotides to control the ribosomal translational process in cells. The oligonucleotide hybridizes to a target RNA to inhibit its translation. In order to prevent the degradation of oligonucleotides by residual and constitutive ribonucleases, various molecular alterations to antisense oligos have been attempted. In this report, evidence is offered that a phosphorothioate-modified 16-mer synthetic oligodeoxynucleotide inhibits the synthesis of O6-methylguanine-DNA methyltransferase (MGMT) in cultured HeLa S3 cells within six hours after introduction.