In a technique known as DNA origami, researchers bend long strands of DNA over and over again to build a variety of tiny 3D structures, including miniature biosensors and drug delivery containers. Launched at the California Institute of Technology in 2006, DNA origami has attracted hundreds of new researchers over the past decade, eager to build vessels and sensors capable of detecting and treating disease in the human body, assess the environmental impact of pollutants and assist in a host of other biological applications.
Although the principles of DNA origami are straightforward, the tools and techniques in the art for designing new structures are not always easy to understand and have not been well documented. Additionally, scientists new to the method had no single point of reference to turn to for the most efficient way to build DNA structures and how to avoid pitfalls that could waste months or even years of research.
That’s why Jacob Majikes and Alex Liddle, researchers at the National Institute of Standards and Technology (NIST) who have studied DNA origami for years, have compiled the first in-depth tutorial on the technique. Their comprehensive report provides a step-by-step guide to designing origami DNA nanostructures, using state-of-the-art tools. Majikes and Liddle described their work in the Jan. 8 issue of National Institute of Standards and Technology Research Journal.
âWe wanted to take all the tools that people have developed and put them all in one place, and explain things that you can’t say in a traditional newspaper article,â said Majikes. âJournal articles can tell you everything everyone did, but they don’t tell you how people did it. “
DNA origami relies on the ability of the complementary base pairs of the DNA molecule to bind to each other. Among the four bases of DNA – adenine (A), cytosine (C), guanine (G) and thymine (T) – A binds with T and G with C. This means that a specific sequence of As, Ts, Cs and Gs will find and bind to its complement.
Bonding allows short strands of DNA to act like “staples”, keeping sections of long strands folded back or joining separate strands. A typical origami design might require 250 staples. In this way, DNA can self-assemble in various forms, forming a nanoscale framework into which an assortment of nanoparticles – many of which are useful in medical treatment, biological research, and environmental monitoring – can be found. ‘to attach.
The challenges of using DNA origami are twofold, said Majikes. First, researchers make 3D structures using a foreign language – base pairs A, G, T, and C. Additionally, they use these base pair staples to twist and untwist the familiar double helix of DNA molecules. so that the strands bend into specific shapes. It can be difficult to imagine and visualize. Majikes and Liddle urge researchers to strengthen their design intuition by building 3D models, such as sculptures made with magnetic bars, before they begin manufacturing. These models, which can reveal which aspects of the folding process are critical and which are less important, should then be “flattened” in 2D to be compatible with computer-aided design tools for DNA origami, which typically use representations. two-dimensional.
DNA folding can be accomplished in a variety of ways, some less efficient than others, noted Majikes. Certain strategies, in fact, can be doomed to failure.
“By highlighting things like ‘You can do this, but it’s not a good idea’ – that type of perspective is not in a traditional newspaper article, but because NIST is focused on driving the ‘State of technology in the nation, we “can publish this work in the journal NIST,” said Majikes. “I don’t think there is another place that would have given us the latitude, the time and the man hours to put it all together.”
Liddle and Majikes plan to continue their work with several additional manuscripts detailing how to successfully fabricate nanoscale devices with DNA.