Logic-Gate-Actuated DNA-Controlled Receptor Assembly for the Programmable Modulation of Cellular Signal Transduction

Angew Chem Int Ed Engl. 2019 Dec 9;58(50):18186-18190. doi: 10.1002/anie.201908971. Epub 2019 Oct 24.

Abstract

Programming cells to sense multiple inputs and activate cellular signal transduction cascades is of great interest. Although this goal has been achieved through the engineering of genetic circuits using synthetic biology tools, a nongenetic and generic approach remains highly demanded. Herein, we present an aptamer-controlled logic receptor assembly for modulating cellular signal transduction. Aptamers were engineered as "robotic arms" to capture target receptors (c-Met and CD71) and a DNA logic assembly functioned as a computer processor to handle multiple inputs. As a result, the DNA assembly brings c-Met and CD71 into close proximity, thus interfering with the ligand-receptor interactions of c-Met and inhibiting its functions. Using this principle, a set of logic gates was created that respond to DNA strands or light irradiation, modulating the c-Met/HGF signal pathways. This simple modular design provides a robust chemical tool for modulating cellular signal transduction.

Keywords: DNA nanotechnology; aptamers; logic gates; receptor assembly; signal transduction.

Publication types

  • Research Support, Non-U.S. Gov't
  • Video-Audio Media

MeSH terms

  • Antigens, CD / metabolism*
  • Aptamers, Nucleotide / chemistry
  • Aptamers, Nucleotide / metabolism*
  • Carbocyanines / chemistry
  • Cell Line
  • Fluorescence Resonance Energy Transfer
  • Hepatocyte Growth Factor / pharmacology
  • Humans
  • Microscopy, Confocal
  • Molecular Probes / chemistry
  • Proto-Oncogene Proteins c-met / metabolism*
  • Receptors, Transferrin / metabolism*
  • Signal Transduction / drug effects
  • Signal Transduction / physiology*

Substances

  • Antigens, CD
  • Aptamers, Nucleotide
  • CD71 antigen
  • Carbocyanines
  • Molecular Probes
  • Receptors, Transferrin
  • cyanine dye 5
  • Hepatocyte Growth Factor
  • Proto-Oncogene Proteins c-met