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Synthetic molecular machines with DNA origami

A prototype synthetic DNA origami structure that can carry protein and DNA cargo has been developed by researchers at UNSW, Sydney.

Challenge

Synthetic biology is an emerging area of science that applies engineering principles to biological systems in order to give them new and useful abilities. This area is usually approached by understanding how natural biological molecules work and then using those principles to design large synthetic molecules, or molecular machines for a range of applications. Designing these molecular machines is one of the core challenges of synthetic biology.

DNA is one tool being used by synthetic biologists to build innovative molecular machines using what is called DNA origami. Through its specific base pairing, DNA can now be designed to fold up into modular blocks that in turn can be put together into many different structures. Researchers can control the behaviours of these machines by controlling the arrangement of the blocks.

RESEARCH

A/Prof. Lawrence Lee and his team at UNSW Sydney are designing a range of molecular machines using DNA origami, based on known biochemical and biophysical principles. One of these is a prototype synthetic DNA origami transporter that can carry protein and DNA cargo, picking up, carrying and dropping off proteins and pieces of DNA. To make cargo bind securely and yet come off when necessary, the team has developed their system using the biochemical principles of DNA base pairing and chemical competition.

They have also generated a polymer of DNA origami bricks, the length of which is automatically controlled through a process called strain accumulation. Distortions gradually accumulate as each block is added until the last block is so distorted that the next block would have to distort beyond its physical capacity and therefore doesn’t bind. The length of the polymer can be controlled by slightly altering the shape of the blocks so that different amounts of strain are introduced.

The team relies on transmission electron microscopy (TEM) at our UNSW facility to visualise and validate their structures.

Transmission electron microscope images of DNA origami transporters. The transporters have a thin central ‘cargo bay’ and thicker end blocks where the attachment sites are located.

Impact

Although the field of DNA nanotechnology and synthetic biology is still in its infancy, by tapping into nature’s blueprints, these researchers are creating exciting new opportunities in the development of bioinspired ‘smart molecules’ that can act autonomously and adapt to changes in their environment. It is easy to foresee applications in molecular diagnostics, targeted drug delivery, vaccine design and agriculture, as well as in many areas that have not yet been imagined.

J. Brown et al., ACS Nano 2022
DOI: 10.1021/acsnano.2c00699

 

Left: TEM images of DNA origami transporters. The transporters have a thin central ‘cargo bay’ and thicker end blocks where the attachment sites are located.
Right: Illustration of DNA transporter with protein cargo, surrounded by other protein subunits in solution. Illustration by Dr Jonathan Berengut, UNSW Sydney.