Mirror-Image DNA\nNanobox for Enhancing Environment\nResistance of Nucleic Acid Probes

Degradation and interference of the nucleic acid probes\nin complex\nbiological environments like cytoplasm or body fluid can cause obvious\nfalse-positive signals and inefficient bioregulation in biosensing\nand biomedicine. To solve this problem, here, we proposed a universal\nstrategy, termed L-DNA assembly mirror-image box-based environment\nresistance (L-AMBER), to protect nucleic acid probes from degradation\nand maintain their responsive activity in complex biological environments.\nStrand displacement reaction (SDR), aptamer, or DNAzyme-based D-DNA\nprobes were encapsulated into an L-DNA box by using an L-D-L block\nDNA carrier strand to construct different kinds of L-AMBER probes.\nWe proved that the L-DNA box could effectively protect the encapsulated\nD-DNA probes by shielding the interference of complex biological environments\nand only allowing small target molecules to enter for recognition.\nCompared with the D-AMBER probes, the L-AMBER probes can realize DNase\nI-assisted amplification detection of biological samples, low false-positive\nbioimaging, and highly efficient miRNA silence in living cells. Therefore,\nL-AMBER provided a universal and effective strategy for enhancing\nthe resistance to environmental interference of nucleic acid probes\nin biosensing and biomedicine applications.