This article has been reviewed according to Science X's editorial process and policies. Editors have highlighted the following attributes while ensuring the content's credibility: Forty-four years ago, Nadrian Seeman published his groundbreaking ideas on using DNA as a structural material, expanding DNA's significance far beyond its role as a carrier of genetic information. Since then, the steadily growing field of DNA nanotechnology has seen numerous innovations.
One was the DNA origami technique, which enables researchers to fold a single long strand of DNA into a desired 2D or 3D shape. The group of William Shih, Ph.D., at the Wyss Institute at Harvard University and Dana-Farber Cancer Institute (DFCI) was the driving force in expanding the initial 2D DNA origami concept into 3D geometries. Their new self-assembly methods allowed them to build 3D multilayered DNA structures that are more stable, rigid and resilient against harsh chemical and biological environments.
DNA nanotechnologists quickly envisioned future devices like new vehicles for targeted drug delivery, autonomously functioning nanorobotic machines and ultra-precise electronic devices. A recent example, the Wyss Institute's DoriVac project, led by Shih, has used DNA origami to precisely organize vaccine components at the nanoscale to enhance immune activation against cancer. However, Shih and other scientists hypothesized that pushing the envelope on the size and 3D complexity of DNA structures even further, while preserving the unique capabilities of DNA origami, could lead to DNA megastructures that could be applied to even more complex tasks.
"The possibility of designing DNA megastructures on the scale of micrometers with features that can be arranged with nanoscale precision could potentially open up paths for sophisticated applications. These include optical devices that can modulate light at visible wavelengths, cell-DNA interfaces that function as 'cell mimics' to program, for example, the behavior of certain immune cells in disease, or molds and scaffolds for assembling tissues with programmable shapes and functions," said Shih, who is a founding core faculty member at the Wyss Institute and professor of biological chemistry and molecular pharmacology at Harvard Medical School and DFCI. In fact, in 2021, his group pioneered a new nanofabrication concept they called "crisscross polymerization" and applied it to weave together DNA nanoribbons from "slats" made of elongated strands of DNA.
Starting from a tiny seed, the ribbons can keep growing until they become several micrometers in length. This new fabrication principle has the potential to be leveraged in diagnostic assays in which the presence of rare biomarkers of disease in patient samples could kickstart a superfast crisscross reaction, resulting in the assembly of an easily detectable DNA nanoribbon as a diagnostic readout. Taking the concept a step further, in 2023 the team applied the principles of crisscross polymerization to build significantly larger and more complex structures, this time using slats made from arrays of entire, interlinked DNA origami structures.
The possible complexity of these "crisscross DNA megastructures" moved the envisioned light, cell and tissue programming technologies closer to reality. "However, there is a difference between demonstrating that something can be done in principle and enabling it to be done with high efficiency, with very low error rates and in many more research labs," said Shih. "The challenge of avoiding unwanted DNA binding events in self-assembling DNA nanostructures just becomes magnified enormously in the fabrication of crisscross DNA megastructures." Discover the latest in science, tech, and space with over 100,000 subscribers who rely on Phys.org for daily insights. d research that matter—daily or weekly.
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