Figure 2.

Schematic representation of a 10-23 DNAzyme with 9×9 arms and modified 3′ terminus. The top panel demonstrates how a DNAzyme can be targeted to cleave the phosphodiester linkage between a selected unpaired purine (uPu) and a paired pyrimidine (Py) by virtue of the nucleotide sequence in its 5′ and 3′ arms, which bind the mRNA through Watson-Crick pairing. The 3′,3′-linked inverted T significantly improves resistance to degradation in biological media. The bottom panel shows the DNAzyme targeting the translational start site of rat Egr-1 mRNA. DNAzyme-dependent cleavage of this sequence can inhibit vascular smooth muscle cell growth in vitro and in vivo (11) and may be of clinical use in blocking neointimal formation in injured arteries, such as occurs in restenosis following angioplasty.