Computer program can translate free-form 2-D drawing into DNA structure – sciencedaily


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Researchers at MIT and Arizona State University have designed a computer program that allows users to translate any free-form drawing into a two-dimensional, nanoscale structure made of DNA.

Until now, designing such structures required technical expertise that puts the process beyond the reach of most people. Using the new program, anyone can create a DNA nanostructure of any shape, for applications in cell biology, photonics, quantum detection and computing, among others.

“This work allows anyone to draw literally any shape in 2D and automatically convert it to DNA origami,” says Mark Bathe, associate professor of bioengineering at MIT and lead author of the study.

The researchers published their findings in the Jan. 4 issue of Scientists progress, and the program, called PERDIX, is available online. The main authors of the article are Hyungmin Jun, postdoctoral fellow at MIT, and Fei Zhang, assistant research professor at Arizona State University. The other authors are MIT Research Associate Tyson Shepherd, recent MIT PhD Holder Sakul Ratanalert, ASU Assistant Researcher Xiaodong Qi, and ASU Professor Hao Yan.

Automated design

DNA origami, the science of folding DNA into tiny structures, originated in the early 1980s, when New York University’s Ned Seeman proposed to take advantage of base pairing abilities. DNA to create arbitrary molecular arrangements. In 2006, Paul Rothemund of Caltech created the first scaffolded two-dimensional DNA structures, weaving a single long strand of DNA (the scaffold) through the shape such as strands of DNA known as “staples. »Hybridize there to help the whole structure retain its shape.

Others then used a similar approach to create complex three-dimensional DNA structures. However, all of these efforts required a complicated manual design to route the scaffold through the entire structure and to generate the staple strand sequences. In 2016, Bathe and his colleagues developed a way to automate the process of generating a 3D blocky DNA structure, and in this new study, they set out to automate the design of arbitrary 2D DNA structures.

To achieve this, they developed a new mathematical approach to the process of routing single stranded scaffolding through the entire structure to form the correct shape. The resulting computer program can take any free-form pattern and translate it into the DNA sequence to create that shape and into sequences for the base strands.

The shape can be sketched in any computer drawing program and then converted to a computer aided design (CAD) file, which is fed into the DNA design program. “Once you have that file, it’s all automatic, much like printing, but here the ink is DNA,” says Bathe.

Once the sequences are generated, the user can order them to easily fabricate the specified shape. In this article, the researchers created shapes in which all the edges are made up of two DNA duplexes, but they also have a working program that can use six duplexes per edge, which are more rigid. The corresponding software tool for 3-D polyhedra, called TALOS, is available online and will soon be published in the journal ACS Nano. The shapes, ranging in size from 10 to 100 nanometers, can remain stable for weeks or months, suspended in a buffer solution.

“The fact that we can design and manufacture them in a very simple way helps solve a major bottleneck in our field,” says Bathe. “Now the field can evolve into much larger groups of people in industry and academia, able to functionalize DNA structures and deploy them for various applications. “

Nanoscale models

Because researchers have such precise control over the structure of synthetic DNA particles, they can attach a variety of other molecules to specific locations. This could be useful for modeling antigens in nanoscale models to shed light on how immune cells recognize and are activated by specific arrangements of antigens found on viruses and bacteria.

“How nanoscale antigen patterns are recognized by immune cells is a very poorly understood area of ​​immunology,” says Bathe. “Attaching antigens to structured DNA surfaces to display them in organized patterns is a powerful way to probe this biology. “

Another key application is the design of light harvesting circuits that mimic the photosynthetic complexes found in plants. To achieve this, researchers attach light-sensitive dyes called chromophores to DNA scaffolds. In addition to harvesting light, such circuits could also be used to perform quantum detection and rudimentary calculations. If successful, these would be the first quantum computing circuits that can operate at room temperature, Bathe says.

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Gordon K. Morehouse