Scientists Use ‘DNA Origami’ to Create ‘Nanomachines’ Capable of Carrying ‘Protein Cargo’

Using a method of DNA manipulation known as “DNA origami” scientists at the University of New South Wales have created “autonomous nanomachines” capable of delivering “protein cargo,” and, potentially, forming “responsive smart materials” that deliver “therapeutic drugs.”

In a paper published in the journal ACS Nano on March 22, 2022, a team of scientists from the University of New South Wales (UNSW) explains how they were able to use a method of DNA manipulation known as “DNA origami” in order to create “autonomous nanomachines” capable of carrying “arbitrary molecular cargo,” including DNA itself, or even proteins. In the future, the University says the DNA machines could form “responsive smart materials to [target] the delivery of therapeutic drugs into diseased cells” in the body. And do “much more.”

In their study the UNSW scientists say they designed and synthesized a “DNA origami receptor that exploits multivalent interactions to form stable complexes that are also capable of rapid subunit exchange.” In other words, the scientists designed nanoscale structures out of single-stranded DNA strands, which themselves were able to receive and bind to DNA “cargo” (i.e. other single-stranded DNA)—as well as maintain a stable overall structure while exchanging out pieces of itself (the “protein subunits”) in order to “adapt to different needs and to [the DNA origami receptors’] changing environment by quickly swapping out molecular components to reconfigure [their] machinery.”

The scientists were able to build their “molecular machines” by folding DNA strands into three-dimensional shapes. This process of “DNA origami”—which is further explained by Nature in the unrelated video immediately above—was pioneered (in its current iteration) by Professor of Computation and Neural Systems at the California Institute of Technology Paul Rothemund. Prior to this study, however, it was only clear DNA nanomachines could carry other DNA cargo, not protein cargo. The authors also note their DNA machines should be generally “compatible with other biomolecules and nanoparticles.” Another first for the field.

“So far, all molecular machines synthesized using DNA nanotechnology [have been] actuated by the exchange of a DNA strand, but exchanging only DNA is a bit limiting,” Professor Lawrence Lee of UNSW Medicine & Health’s EMBL Australia Node in Single Molecule Science said in the University’s press release discussing the study. Lee, the lead author on the study, added that “Our findings expand the functional complexity available for DNA nanotechnology.”

Images of nanoscale DNA origami structures from another, unrelated study in Nature Communications. Image: Jonathan List, Elisabeth Falgenhauer, Enzo Kopperger, Günther Pardatscher & Friedrich C. Simmel

Incredibly, Lee et al.’s nanomachines are also able to switch out the cargo they’re carrying. The “cargo,” whether it be DNA or the amino acids of a protein, “binds at multiple sites to the DNA receptor, and can be displaced by new cargo via a competitive-binding process, when other cargo is present in solution.”

“Rapid exchange and maintaining high stability seem to be two incompatible states, yet there are so many of nature’s nanoscale machines that behave in this way,” Lee added in the press release.

Indeed, the scientists’ DNA origami receptor works similarly to, and is inspired by, a DNA replisome. As ScienceDirect notes a replisome is “the DNA copy machine” within a biological cell that contains the enzymes necessary to unwind and copy DNA, as well as process its “lagging strand.” UNSW notes, in fact, that “The competitive exchange mechanism used by the replisome to simultaneously achieve [structural stability and rapid subunit exchange] was proposed in an earlier publication in Nucleic Acid Research in May of 2019.

A diagram of a replisome. Image: LadyofHats Mariana Ruiz 

The University ends its coverage of the study by noting that “The field of DNA nanotechnology is still in its infancy.” Although perhaps the field has actually aged into the “young child” phase since R A Freitas Jr created artificial red blood cells with “onboard nanocomputer[s]” and “numerous chemical and pressure censors” back in July of 1998.

Feature image: Jonathan List, et al. / Nature

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