Tag Archives: DNA origami

Not your sister’s art hobby: DNA origami can save lives

Increasingly, origami (the Japanese art of paper folding) is becoming less of an artistic concern and more of a scientific one. The California Institute of Technology made special news in 2006 about a way to weave DNA strands into any two-dimensional shape or figure. Caltech’s Paul Rothemund called it “DNA origami” — but that was just the start of it.

Image credits: Nikoline Arns.

Imagine strands of DNA folded back and forth, forming a scaffold that fills the outline of a desired shape. Then, imagine more DNA strands specially designed to bind to that scaffold.

Rothemund, the strand-weaver, explained why this was useful. Scientists would find it easy to create and study any complex nanostructures they might want. Quoted in a 2006 press release, in he said he came up with a half a dozen shapes, including square, triangle, five-pointed star, and smiley face.

“At this point, high-school students could use the design program to create whatever shape they desired,” Rothemund said at the time.

Nature News said the binders, DNA ‘staples,’ were short strands “that stop the viral strand from unraveling,” adding that the method could find use in molecular biology and electronics. “The technique could be used to build a flat scaffold to carry microscopic electronic components. Enzymes could also be attached, creating a tiny protein factory,” the article emphasized.

In 2016, Caltech shed new light on the discovery. “The publication of Paul Rothemund’s paper on DNA origami (Nature, March 16, 2006) marked a turning point in DNA nanotechnology, enabling unprecedented control over designed molecular structures.”

Step by step

DNA origami object from viral DNA visualized by electron tomography. Image credits: OrigamiMonkey / Wikipedia.

Well, it’s 2021 and better late than never. The latest news about DNA origami is that Jacob Majikes and Alex Liddle, researchers at the National Institute of Standards and Technology (NIST), having stayed with the topic of DNA origami for years, have compiled a detailed tutorial on the technique. “DNA Origami Design: A How-To Tutorial” has been published in the Journal of Research of the National Institute of Standards and Technology. Majikes and Liddle have provided a step-by-step guide on the design of DNA origami nanostructures, making it easier than ever to design and use this type of structure.

Over the years, the method had attracted hundreds of researchers, said NIST, and for various reasons: Some may be interested in order to detect and treat diseases, or, to assess pollutants’ impacts on the environment and other applications. The two guide authors explained what they did. Namely, they went for the ‘how.’

“We wanted to take all the tools that people have developed and put them all in one place, and to explain things that you can’t say in a traditional journal article,” said Majikes. “Review papers might tell you everything that everyone’s done, but they don’t tell you how the people did it.”

Their journal paper further stated what was needed:

While the design and assembly of DNA origami are straightforward, its relative novelty as a nanofabrication technique means that the tools and methods for designing new structures have not been codified as well as they have for more mature technologies, such as integrated circuits. While design approaches cannot be truly formalized until design-property relationships are fully understood, this document attempts to provide a step-by-step guide to designing DNA origami nanostructures using the tools available at the current state of the art.”

Many potential applications of DNA origami have been suggested in literature, including drug delivery systems and nanotechnological self-assembly of materials, so this is not just some ethereal approach, it has clinical use. For instance, Harvard University Wyss Institute researchers reported the self-assembling and self-destructing drug delivery vessels using the DNA origami in lab tests, and another team of researchers from China and the US created a DNA origami delivery vehicle for Doxorubicin, a commonly used anti-cancer drug. So when someone acts like origami is just cute art, tell them that’s not nearly the case — it could be a real lifesaver.

Glowing DNA origami used to recreate Van Gogh’s ‘Starry Night’

Image credit Ashwin Gopinath/Caltech

Image credit Ashwin Gopinath/Caltech

In a unique study that intertwines science and art, researchers from the California Institute of Technology (Caltech) used a technique called DNA origami to recreate the famous “The Starry Night” painting created by artist Vincent Van Gogh.

Caltech scientist Paul Rothemund created the DNA origami technique 10 years ago to fold and manipulate a long strand of DNA into any shape, acting as a scaffold that can be used to organize components on the nanoscale.

Since its initial creation, Rothenmund and his team have refined the DNA origami technique into what it is today, using electron-beam lithography to engrave binding sites that mirror the origami’s shape. The new study is the first example of their enhancements of the technique, exhibiting its ability to put fluorescent molecules into tiny light sources, a process that Rothenmund compares to screwing light bulbs into lamps.

In the study, the lamps are phototonic crystal cavities (PCCs), microscopic defects within a honeycomb of holes that are designed to resonate at a specific wavelength of light. The team aligned the PCCs into a checkerboard pattern, altering the glowing intensity of each one to create the piece of art

“A fluorescent molecule tuned to the same color as a PCC actually glows more brightly inside the cavity, but the strength of this coupling effect depends strongly on the molecule’s position within the cavity,” said Ashwin Gopinath, a senior postdoctoral scholar in bioengineering at Caltech and lead author of the study. “A few tens of nanometers is the difference between the molecule glowing brightly, or not at all.”

In addition to creating art, DNA origami has the potential to influence numerous fields of research including nanoscale computer construction and drug delivery. As of now, scientists are working to improve the longevity of the light emitters.

Journal Reference: Engineering and mapping nanocavity emission via precision placement of DNA origami. 11 July 2016. 10.1038/nature18287

DNA hinges

Nano-machines made from DNA look like molecule-size hinges

For the very first time, engineers have used the DNA origami assembly method to build  complex DNA-based mechanism that performs a repeatable and reversible function. Mechanical engineers at The Ohio State University built their devices such that they may function like any regular macro-object, like opening and closing hinges. Their approach, however, is different than other DNA assembly projects which concentrated on mimicking biological systems or static shapes. Such dynamic molecule-sized devices could be used in smart drug delivery or self-assembling tiny transformers-like robots.

DNA origami hinges

DNA hinges

The DNA origami method for making nano-structures has been widely used since 2006, and is now a standard procedure for many labs that are developing future drug delivery systems and electronics. It involves taking long strands of DNA and coaxing them to fold into different shapes, then securing certain parts together with “staples” made from shorter DNA strands. The resulting structure is stable enough to perform a basic task, such as carrying a small amount of medicine inside a container-like DNA structure and opening the container to release it.

[RELATED] Nanorobots made out of DNA seek and kill cancer cells

“Nature has produced incredibly complex molecular machines at the nanoscale, and a major goal of bio-nanotechnology is to reproduce their function synthetically,” saidCarlos Castro, the group project leader and an assistant professor of mechanical and aerospace engineering. “In essence, we are using a bio-molecular system to mimic large-scale engineering systems to achieve the same goal of developing molecular machines.”

A DNA origami piston. Credit:  Ohio State University.

A DNA origami piston. Credit: Ohio State University.

To get their DNA machines to function properly, the engineers designed the flexing parts out of single-stranded DNA, while those regions that were supposed to be stiff were built from snips of double-stranded DNA. In the case of hinges that repeatedly open and close, this also had to perform their operation reversibly, so the engineers attached small strands of synthetic DNA off the side of the main components. Like a hook-and-loop fastener, the strands latch onto each other when the device is closed and release when opened. To control the operations of the machine, researchers make changes to the chemical environment. The machines then respond to this stimuli accordingly.

“DNA origami enables the precise fabrication of nanoscale geometries,” the authors write. “We demonstrate an approach to engineer complex and reversible motion of nanoscale DNA origami machine elements…Our results demonstrate programmable motion of 2-D and 3-D DNA origami mechanisms constructed following a macroscopic machine design approach.”

origami hinge

This approach of designing simple joints and connecting them together to make more complex working systems is common in macroscopic machine design, but this is the first time it’s been done with DNA—and the first time anyone has tuned the DNA to produce reversible actuation of a complex mechanism, as described in a paper published in  Proceedings of the National Academy of Sciences.

“I’m pretty excited by this idea,” Castro said. “I do think we can ultimately build something like a Transformer system, though maybe not quite like in the movies. I think of it more as a nano-machine that can detect signals such as the binding of a biomolecule, process information based on those signals, and then respond accordingly—maybe by generating a force or changing shape.”

 

Programmed to Fold: RNA Origami

A team of researchers from the Aarhus University in Denmark and CalTech has developed an origami-inspired method of organizing molecules on the nanoscale. The team has modeled RNA, DNA’s close cousin into complicated shapes using the technique.

This illustration is an artist’s impression of RNA nanostructures that fold up while they are being synthesized by polymerase enzymes. Image credits: Cody Geary.

Together with DNA, RNA comprises the nucleic acids, which, along with proteins, constitute the three major macromolecules essential for all known forms of life. DNA origami is not a novel technique, but RNA origami is, and the process of creating the two is fundamentally different. While with DNA, you chemically synthesize it and then arrange it into any shape you want, with RNA, you have to fold up its components as you synthesize them – under conditions similar to living organisms. These features of RNA origami may allow designer RNA structures to be grown within living cells.

“The parts for a DNA origami cannot easily be written into the genome of an organism. An RNA origami, on the other hand, can be represented as a DNA gene, which in cells is transcribed into RNA by a protein machine called RNA polymerase,” explains Paul Rothemund, a senior research associate in computation and neural systems in the Division of Engineering and Applied Science at Caltech.

They first demonstrated the technique by assembling RNA into rectangles, and then assembled the rectangles in a honeycomb-like pattern.

“What is unique about the method is that the folding recipe is encoded into the molecule itself, through its sequence.” explains first author Cody Geary, a postdoctoral scholar at Aarhus University.

This means that the shape of the resulting RNA is actually determined by the synthesized RNA sequence. This can have a myriad of potential applications in biology, most notably in protein delivery.

“RNA has a richer structural and functional repertoire than DNA, and so I am especially interested in how complex biological motifs with special 3-D geometries or protein-binding regions can be added to the basic architecture of RNA origami,” says Geary, who completed his BS in chemistry at Caltech in 2003.

Also, unlike DNA origami, RNA can be made much more cheaper and faster, which makes it even more interesting:

“The payoff is that unlike DNA origami, which are expensive and have to be made outside of cells, RNA origami should be able to be grown cheaply in large quantities, simply by growing bacteria with genes for them,” he adds. “Genes and bacteria cost essentially nothing to share, and so RNA origami will be easily exchanged between scientists.”

Origami techniques have gotten a lot of attention in science lately. Aside for the DNA manipulation technique, we’ve seen several types of origami robots, including DNA nanobots, space shuttles,  and even origami microscopes. Personally, I find the mixture of art and science remarkable in general, and even more so in this case.