Building big with DNA gets a software upgrade
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…
In 1946, Nadrian Seeman first proposed the idea of using DNA as a structural material, elevating its significance beyond being merely a genetic carrier. Since then, DNA nanotechnology has progressed significantly, with one notable advancement being the DNA origami technique. This method allows researchers to fold a single long DNA strand into a desired 2D or 3D shape.
The innovative group led by William Shih at the Wyss Institute at Harvard University and Dana-Farber Cancer Institute has taken this concept further, creating 3D, multilayered DNA structures that are more robust and resistant to harsh conditions.
Scientists have envisioned potential applications of DNA nanotechnology, including targeted drug delivery vehicles, functional nanorobotic machines, and ultra-precise electronic devices. For instance, Shih's DoriVac project utilized DNA origami to organize vaccine components at the nanoscale, enhancing immune activation against cancer.
However, Shih and colleagues theorized that pushing the boundaries of DNA structure size and complexity, while maintaining DNA origami's unique capabilities, could lead to the creation of DNA megastructures. These structures, on the scale of micrometers with nanoscale precision, could enable sophisticated applications, such as optical devices for light modulation, cell-DNA interfaces to program immune cell behavior in diseases, or molds and scaffolds for assembling programmable tissues.
In 2021, Shih's group introduced a new nanofabrication method called crisscross polymerization. This technique enables the weaving of DNA nanoribbons from elongated strands, with the ribbons growing from a tiny seed to several micrometers in length. Building on this concept, the team created significantly larger and more complex structures using slats made from arrays of entire, interlinked DNA origami structures, making light, cell, and tissue programming technologies closer to reality.
Nevertheless, designing and fabricating crisscross DNA megastructures poses challenges due to the need to avoid unwanted DNA binding events, which become increasingly complex as the structures grow in size and intricacy. Now, Shih's team, including research fellows Matthew Aquilina and Florian Katzmeier, has published a computational framework in Nature Communications, aiming to make the fabrication of crisscross DNA megastructures more accessible and user-friendly.
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