Strand
displacement reactions are important bricks for the construction
of various DNA nanodevices, among which the toehold-mediated strand
displacement reaction is the most prevalently adopted. However, only
a limited number of tools could be used to finely regulate the toehold
reaction, thus restricting DNA nanodevices from being more multifunctional
and powerful. Herein, we developed a regulation tool, Clip, and achieved
multiple regulatory functions, including subtle adjustment of the
reaction rates, allosteric strand displacement, selective activation,
and resetting of the reaction. Taking advantages of the multiple functions,
we constructed Clip-toehold-based DNA walking machines. They showed
behaviors of controllable walking, concatenation, and programmable
pathways. Furthermore, we built Clip-toehold-based AND and OR logic
gates and integrated those logic gates to construct multilayer circuits,
which could be reset and reused to process different input signals.
We believe that the proposed Clip tool has expanded the functionality
of DNA strand displacement-based nanodevices to a much more complex
and diverse level and anticipate that the tool will be widely adopted
in DNA nanotechnology.
Toehold-mediated strand displacement and its regulatory tools are fundamental for DNA nanotechnology. However, current regulatory tools all need to change the original sequence of reactants, making the regulation inconvenient and cumbersome. More importantly, the booming development of DNA nanotechnology will soon promote the production of packaged and batched devices or circuits with specified functions. Regarding standardized, packaged DNA nanodevices, access to personalized post-modification will greatly help users, whereas none of the current regulatory tools can provide such access, which has greatly constrained DNA nanodevices from becoming more powerful and practical. Herein, we developed a novel regulation tool named Cap which has two basic functions of subtle regulation of the reaction rate and erasability. Based on these functions, we further developed three advanced functions. Through integration of all functions of Cap and its distinct advantage of working independently, we finally realized personalized tailor-made post-modification on pre-fabricated DNA circuits. A pre-fabricated dual-output DNA circuit was successfully transformed into an equal-output circuit, a signal-antagonist circuit and a covariant circuit according to our requirements. Taken together, Cap is easy to design and generalizable for all strand displacement-based DNA nanodevices. We believe the Cap tool will be widely used in regulating reaction networks and personalized tailor-made post-modification of DNA nanodevices.
Branch migration-based PCR combined with endonuclease IV-assisted target recycling probe/blocker system for highly selective detection of low-abundance mutations.
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