Modulation of ras expression by anti-sense, nonionic deoxyoligonucleotide analogs

Anti-ras oligodeoxyribonucleoside methylphosphonates (ONMP's) complementary to the initiation codon region have been synthesized to explore their efficacy and specificity on ras-p21 translation. ONMP (IC-0) precisely complementing the first initial 11 nucleotides of the Balb-ras initiation codon region acts in a dose-dependent manner to inhibit p21 translation by a rabbit reticulocyte lysate. At 100 microM, IC-0 inhibits the cell-free translation of p21 close to completion. The two control oligomers containing one or two nucleotide mismatches were significantly less effective than IC-0 at the equivalent concentration. In living cells, a perfectly matched ONMP directed against the initiation codon region inhibited Ha-ras p21 expression by 90% at a concentration of 50 microM.