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Residue replacement of functional nucleic acids is the first choice for their structure-activity relationship and better performance,in the absence of active conformation.Two small DNAzymes,10-23 as genetic therapeutics against many disease-related genes and 8-17 DNAzyme as biosensors,have been studied extensively.Canonical residue replacement and deletion confirmed the conservation of the catalytic cores,and no better analogs could be obtained by this way.