Significance: Sequence-specific targeting of disease-associated RNAs by new types of chemically modified antisense oligonucleotides with improved physicochemical and biological properties is still in high demand. miRNA-addressing mesyl phosphoramidate oligonucleotides represent prospective therapeutics since they reveal good bioavailability in tumor tissue, potent and long-lasting antitumor effect, high targeted specificity associated with reactivation of tumor suppressor proteins, and physiological safety.