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Tiny machines made of DNA origami may make antibiotics work better

Miniature devices made from intricately folded DNA strings can boost the potency of antibacterial chemicals by bringing individual molecules into direct contact with the microbes
DNA origami
E. coli bacteria (in red) coated with DNA origami nanostructures (in green)
Courtesy Ioanna Mela

Origami isn’t usually thought of as a weapon – but it can be deadly when it is made of DNA. Tiny devices made from intricately folded DNA strands can boost the potency of antibacterial chemicals by bringing individual molecules into direct contact with microbes.

When tested on two common kinds of bacteria, the folded DNA slowed their growth rate. Ioanna Mela at the University of Cambridge says the approach could be directed against any kind of microbe. “This is proof of principle,” she says.

DNA is best known for storing our genetic information, but it has other useful properties. One is that it can be folded into complex 3-D structures to make any desired pattern, known as DNA origami. Another is that small lengths of DNA can be designed to have the exact shape needed to bind to other biological molecules, like a key fitting into a lock.

Mela’s team combined these two functions to create a bacteria-killing machine in the form of a flat platform of DNA with five wells, each loaded with two molecules of lysozyme, an antibacterial compound found in body fluids such as tears. Sticking out from the edges of the platform are many short lengths of DNA designed to bind to E. coli or Bacillus subtilis bacteria.

The idea is that the platforms lock on to bacteria and hold them close to the lysozyme, increasing its potency. Sure enough, when bacteria were exposed to the platforms, they grew more slowly than when exposed to the antibacterial compound alone.

Using the approach for an antibiotic drug would allow lower doses to be given, reducing side effects for individuals and slowing the rise of antibiotic resistance in general, says Mela.

The team will also try adding more than one kind of antibiotic to each well. “We can attach or take away active components from the same nanostructure without much time or cost constraints,” says Mela.

“This is a nice application of using the modularity of DNA nanotech – you can incorporate different ingredients,” says Philip Tinnefeld at the Ludwig Maximilian University of Munich in Germany. One potential flaw is that DNA structures tend to get broken down by enzymes in the blood, although they can be chemically modified to make them more stable, he says.

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Topics: Antibiotics / infectious disease