DNA computing function switching by programming base stacking interactions with minimal molecular architecture changes

In biological systems, molecular network functionalities are usually switched in a flexible, facile, and programmable manner. Mimicking this, substantial studies are directed towards developing synthetic DNA networks that exhibit similar function-switching capabilities, though often hindered by extensive molecular architecture changes and stringent condition controls, which result in a time-consuming and labor-intensive process. Here, we develop a base stacking-mediated allostery strategy to manipulate the DNA computing function switching with minimal molecular architecture changes, usually as few as 1-2 nucleotide changes. We implement up to 20 distinct logic function switching within DNAzyme networks. We also validate our function switching platform to implement totally 84 kinds of gene regulation patterns in cancer cell lines, demonstrating its utility in RNA sensing and green fluorescent protein regulation. This strategy offers a simplified alternative approach to enrich DNA regulations, with potential applications in DNA computing and bioengineering.