A nucleic acid logic gate system that distinguishes different sets of inputs from one miRNA collection with shared members

Abstract

A proof-of-principle logic system was established to process multi-input and multi-output logic relationships with the aim of identifying the tissue origins of cancer in light of their established relationships with miRNA distributions. The system detected two characteristic miRNA sets from a collection with two gates, each identifying a set of three input miRNAs, with miRNAs members shared among the two sets. The design of the logic system featured three stages: the initialization stage, the logic stage, and the signal stage. The initialization stage transduced each inputted miRNA into a messenger DNA in multiplied quantities. In the logic stage, the two logic gates were implemented; each picked up one set of inputted miRNA and produced the according RCA product. In the signal stage, the RCA products from the two gates were labelled with respective Raman tags, and the according SERS signal for each gate was produced. The logic system provided amplification for the miRNA inputs and thus was capable of processing miRNA with low abundance. The designed logic behavior was also verified to ensure that each gate only reacted to its specific input set, and the shared miRNA inputs could be processed by both gates. It was also verified that mismatched miRNA inputs did not interfere with the designed logic behaviors.