Table 1.

Advantages and disadvantages of different structural modifications used in DNAzymes.

Structural modification	Advantages	Disadvantages	Key points	References
3′-3′ inverted nucleotide at the 3′ end	Increase stability and enhance catalytic activity	Slower product release rate	Counteract the degradation by 3′-exonucleases	[15, 142–144]
Phosphorothioate linkages	Increase stability	Affect cleavage efficiency, toxicity, and immunologic responsiveness and produce sequence-independent effects	Substitution of oxygen atoms with sulfur atoms affects the DNAzyme structure in a molecularity-dependent manner Counteract the degradation by exonucleases	[142–144]
Locked nucleic acids	Increase affinity for complementary sequence, increase stability, solubility, easily automated synthesis, and straightforward cellular delivery	Influence catalytic activity and biological potency	Increase in stability due to efficient base stacking by adopting A-form geometry and oxymethylene bridge link between 2′ and 4′ carbon atoms of a furanose ring Charged backbone facilitating lucid cellular transfection A change in the charge distribution of the minor groove wall furnish solvation properties	[142, 143, 145]