NIST Creates A "How-To Tutorial" for DNA Origami

With the increased interest surrounding the design and fabrication of DNA origami nanostructures, the National Institute of Standards and Technology (NIST) has published a guide for beginners using existing technologies.

Researchers Jacob Majikes and Alex Lidde from NIST, who have both studied the emerging DNA origami tech for years, compiled their acquired know-how in "DNA Origami Design: A How-To Tutorial," published in the Journal of Research of the National Institute of Standards and Technology, January 8.

"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," Majikes said in a NIST news release. He also explains that while published papers might provide an update on what has been achieved in the field, "they don't tell you how the people did it."

DNA Origami, Revolutionizing Medicine and Biology

In DNA origami, long strands of DNA are folded in iterations to fabricate various 3D nanostructures, which are then used to create miniature versions of biosensors and drug-delivery receptacles. The concept of utilizing DNA as a fabrication material was first introduced in the 1980s by nanotechnologist and crystallographer Nadrian C. Seeman. However, the current method widely used today has been pioneered by Paul Rothemund, researcher professor at the California Institute of Technology, in 2006. Since then, it has attracted studies and advancements for various biomedical applications - detection and treatment of diseases, assessment of external factors such as pollutants, drug delivery, and more.

DNA origami primarily relies on the complementary base pairs of the deoxyribonucleic acid to bind to one another. Adenine (A) binds with thymine (T), and guanine (G) binds with cytosine © - with specific sequences of these bases that will bind to their complement. Connecting these DNA components creates short strands that work as "staples," which are used to connect longer strands of DNA.

While its principles appear simple and straightforward, there has been a lack of documentation on how existing designs and methods are achieved, prompting NIST researchers to publish the report. NIST researchers aim to create a single, unified reference for future researchers hoping to work into the tech.

Accessible for Beginners

The NIST tutorial details the target audience, "novice designers of DNA origami systems," mostly on undergraduate or post-graduate studies. It also notes that the target readers for the "how-to tutorial" are expected to be familiar with DNA concepts: physical properties of B-DNA, single-stranded DNA (ssDNA), crossover junctions, and more.

For the "tools" required, aside from computing equipment and 'craft supplies for macroscale models," a DNA nanotech computer-aided design (CAD) software is necessary. The guide then lays down principles behind the technology and basic concepts crucial for beginners to start designing their own DNA-based nanostructures.

"Pointing out things like 'You could do this, but it's not a good idea'-that type of perspective isn't in a traditional journal article, but because NIST is focused on driving the state of technology in the nation, we're able to publish this work in the NIST journal," Majikes added.