Table 1.

Summary of DNAzyme Chemical Modifications, Indicating Advantages and Disadvantages of Each

Chemical modification	Advantage	Disadvantage	References
3′-inverted dT	Improved stability Does not disrupt catalytic function Can improve cleavage	Relatively short half-life	[1,40–43]
Phosphorothioate (PS)	Improved stability Increases cellular uptake	Decrease substrate affinity Toxic side effects	[1,36,42,44–49]
2′-O-methyl (2′-O-Me)	Improved stability Can be incorporated into core	Reduced cleavage ability	[37,38]
Locked nucleic acid (LNA)	Improved base pairing selectivity and efficiency Reduced sequence length Improved stability Improves binding to highly structured RNAs	Inflexible/rigid structure Reduced cleavage ability Reduced multiple turnover	[1,37,50–52]
2′-O-(N-(aminoethyl)carbamoyl) methyl	Improved catalytic function		[53–56]
2′-deoxyadenosine analogues	Improved catalytic function		[57]
2′deoxyuridine derivative containing a guanidinium group	Reduced negative charge (increased cellular uptake)	May reduce catalytic ability	[58]
Phosphorodiamidate morpholino oligonucleotides (PMO)	Improved stability Excellent safety profile	Has not been applied to DNAzymes May lower catalytic ability Reduced binding affinity	[59]
2′-fluoroarabino nucleic acid (FANA) and α-l-threofuranosyl nucleic acid backbone (XNA)	Improved catalytic function Improved stability Allele specificity		[60,61]