Mimicking viruses from inside out using DNA origami

The cover of the current issue of ACS Synthetic Biology highlights our collaborative research project with UCL Chemistry and the National Physical Laboratory to engineer a programmable inside-out “virus”. This everted “virus” is designed to deliver functional proteins into live cells.

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ACS Synthetic Biology Cover: March 2018 Issue

DNA origami viruses inside endosomes. Upon escaping endosomes, the viruses release green fluorescent protein (GFP) inside the cell. The background of the Figure denotes an intracellular environment, with spheres depicting endosomes, blue boxes DNA origami and green particles  GFP.

The synthetic virus is formed of a DNA origami shell, decorated with HIV-Tat protein transduction domains which promote its uptake into live cells. The DNA origami shell is box-like in structure, incorporating a lid with a pH switchable locking mechanism. As the lid opens in response to intracellular pH changes, the encapsulated proteins are released into the cell.

To determine the topology of the nanoscale DNA origami virus shell, Alice utilised high resolution Atomic Force Microscopy (AFM) to determine the dimensions of the DNA origami shell in a native-like environment.

   
  
   
  
    
  
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   DNA Origami Inside-Out Virus in closed (left) and open (right) states. Top: schematic showing the DNA origami shell (grey) decorated with HIV-Tat proteins (red) and containing fluorescent protein cargo (green). Bottom, Atomic Force Microscopy images showing the DNA origami shell both states. 

DNA Origami Inside-Out Virus in closed (left) and open (right) states. Top: schematic showing the DNA origami shell (grey) decorated with HIV-Tat proteins (red) and containing fluorescent protein cargo (green). Bottom, Atomic Force Microscopy images showing the DNA origami shell both states. 

The work was kindly funded by the Engineering and Physical Sciences Research Council (EPSRC) in the form of a Doctoral Prize fellowship to Alice and by the UK’s Department for Business, Energy and Industrial Strategy.