Small Molecule Release and Activation through DNA Computing

Abstract

DNA-based logic gates can be assembled into computational devices that generate a specific output signal in response to oligonucleotide input patterns. The ability to interface with biological and chemical environments makes DNA computation a promising technology for monitoring cellular systems. However, DNA logic gate circuits typically provide a single-stranded oligonucleotide output, limiting the ability to effect biology. Here, we introduce a novel DNA logic gate design capable of yielding a small molecule output signal. Employing a Staudinger reduction as a trigger for the release and activation of a small molecule fluorophore, we constructed AND and OR logic gates that respond to synthetic microRNA (miRNA) inputs. Connecting the gates in series led to more complex DNA circuits that provided a small molecule output in response to a specific pattern of three different miRNAs. Moreover, our gate design can be readily multiplexed as demonstrated by simultaneous small molecule activation from two independent DNA circuits.

Coupling of DNA Circuit and Templated Reactions for Quadratic Amplification and Release of Functional Molecules

“…[4][5] Strand displacement mechanisms have been used to engineer networks capable of solving mathematical operations and circuits capable of amplification or molecular motion. [6][7][8][9][10][11][12][13][14][15] In parallel, DNA-templated reactions have also been shown to be a powerful strategy to translate a nucleic acid cue into a chemical reaction. [16][17] Whereas the output of strand-displacement networks are inherently oligonucleotides, 18 templated reactions can be used to uncage or synthesize functional molecules.…”

Design, Bioanalytical, and Biomedical Applications of Aptamer-Based Hydrogels

“…Comparing this to silicon-based computation, although many challenges in designing computation devices, aptamer-based hydrogels logic circuits are still developing with great rapidity, due to their stability, biocompatibility, and predictable structure (143)(144)(145)(146). Yin et al (147) exploited a hydrogel structure based on hybridization behavior between crosslinker strands with aptamer sequences of ATP and cocaine molecules onto polymer chains.…”

Recent Progress in Fluorescence Signal Design for DNA‐Based Logic Circuits

“…Although most logic systems based on strand‐displacement reaction employ the FRET signal strategy, other signal producing mechanisms are still being investigated. Deiters and co‐workers reported a logic system that contains oligonucleotides modified with 7‐amino‐4‐methyl coumarin (AMC) and phosphine separately, the hybridization of which triggers the Staudinger reaction partners into close proximity and yielded small molecular output signals. The mechanism is quite like FRET, but the system offers turned‐on fluorescence signal by hybridization.…”

“…iii)The structure of the phosphine, 2DPBM. iv) The normalized AMC fluorescence and the truthtable of the AND gate.Reprinted from reference[45],C opyright,2017, American Chemical Society.…”