Small Molecule Release and Activation through DNA Computing

J Am Chem Soc. 2017 Oct 4;139(39):13909-13915. doi: 10.1021/jacs.7b07831. Epub 2017 Sep 25.

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.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Computers, Molecular*
  • DNA / chemistry*
  • MicroRNAs / chemical synthesis
  • MicroRNAs / chemistry
  • Small Molecule Libraries / chemistry*

Substances

  • MicroRNAs
  • Small Molecule Libraries
  • DNA