Catalytic activity of DNAzymes targeted to IGF-I and MDR1 mRNA can be regulated by the combination of 10-23 DNAzyme with 3'-modified oligo(2'-O-methylribonucleotides) that are favorable as effectors due to their high affinity to RNA and nuclease resistance. We have demonstrated that the DNAzyme constructions designed were able to bind and cleave long structured RNA transcripts effectively under simulated physiological conditions.