DNA assembly is approaching 3D-printing levels of convenience

dna
Digizyne/MIT

Original news release was published by MIT, written by Helen Knight.

Researchers can build complex, nanometer-scale structures of almost any shape and form, using strands of DNA. But these particles must be designed by hand, in a complex and laborious process. This has limited the technique, known as DNA origami, to just a small group of experts in the field.

Now a team of researchers at MIT and elsewhere has developed an algorithm that can build these DNA nanoparticles automatically.

In this way the algorithm, which is reported together with a novel synthesis approach in the journal Science this week, could allow the technique to be used to develop nanoparticles for a much broader range of applications, including scaffolds for vaccines, carriers for gene editing tools, and in archival memory storage.

Unlike traditional DNA origami, in which the structure is built up manually by hand, the algorithm starts with a simple, 3-D geometric representation of the final shape of the object. It then decides how it should be assembled from DNA, according to Mark Bathe, an associate professor of biological engineering at MIT, who led the research.

“The paper turns the problem around from one in which an expert designs the DNA needed to synthesize the object, to one in which the object itself is the starting point, with the DNA sequences that are needed automatically defined by the algorithm,” Bathe says.

“Our hope is that this automation significantly broadens participation of others in the use of this powerful molecular design paradigm.”

The algorithm first represents the object as a perfectly smooth, continuous outline of its surface. It then breaks the surface up into a series of polygonal shapes. Next, it routes a long, single strand of DNA, called the scaffold, which acts like a piece of thread, throughout the entire structure to hold it together. The algorithm weaves the scaffold in one fast and efficient step, which can be used for any shape of 3-D object, Bathe says.

The algorithm, which is known as DAEDALUS (DNA Origami Sequence Design Algorithm for User-defined Structures), can build any type of 3-D shape, provided it has a closed surface.

The researchers are now investigating a number of applications for the DNA nanoparticles built by the DAEDALUS algorithm. One such application is a scaffold for viral peptides and proteins for use as vaccines.

The researchers demonstrated that the DNA nanoparticles are stable for more than six hours in serum, and are now attempting to increase their stability further. The team is also investigating the use of the nanoparticles as DNA memory blocks. Previous research has shown that information can be stored in DNA, in a similar way to the 0s and 1s used to store data digitally. The information to be stored is “written” using DNA synthesis and can then be read back using DNA sequencing technology.

The most exciting aspect of the work, however, is that it should significantly broaden participation in the application of this technology, Bathe says, much like 3-D printing has done for complex 3-D geometric models at the macroscopic scale.

Michal Dudic

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