Nav: Home

DNA design that anyone can do

January 03, 2019

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 has required technical expertise that puts the process out of reach of most people. Using the new program, anyone can create a DNA nanostructure of any shape, for applications in cell biology, photonics, and quantum sensing and computing, among many others.

"What this work does is allow anyone to draw literally any 2-D shape and convert it into DNA origami automatically," says Mark Bathe, an associate professor of biological engineering at MIT and the senior author of the study.

The researchers published their findings in the Jan. 4 issue of Science Advances, and the program, called PERDIX, is available online. The lead authors of the paper are Hyungmin Jun, an MIT postdoc, and Fei Zhang, an assistant research professor at Arizona State University. Other authors are MIT research associate Tyson Shepherd, recent MIT PhD recipient Sakul Ratanalert, ASU assistant research scientist 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 Ned Seeman of New York University proposed taking advantage of DNA's base-pairing abilities to create arbitrary molecular arrangements. In 2006, Paul Rothemund of Caltech created the first scaffolded, two-dimensional DNA structures, by weaving a long single strand of DNA (the scaffold) through the shape such that DNA strands known as "staples" would hybridize to it to help the overall structure maintain its shape.

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

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

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

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

"The fact that we can design and fabricate these in a very simple way helps to solve a major bottleneck in our field," Bathe says. "Now the field can transition toward much broader groups of people in industry and academia being able to functionalize DNA structures and deploy them for diverse applications."

Nanoscale patterns

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

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

Another key application is designing light-harvesting circuits that mimic the photosynthetic complexes found in plants. To achieve that, the researchers are attaching light-sensitive dyes known as chromophores to DNA scaffolds. In addition to harvesting light, such circuits could also be used to perform quantum sensing and rudimentary computations. If successful, these would be the first quantum computing circuits that can operate at room temperature, Bathe says.
-end-
Bathe and three other MIT faculty members -- Gabriela Schlau-Cohen, Adam Willard, and Dirk Englund -- recently received a National Science Foundation grant to pursue this quantum sensing and computing project.

Other possible applications for the DNA structures include using them to help organize macromolecular protein assemblies found in cells, so that they can be more easily imaged with high-resolution cryo-electron-microscopy. MIT's new MIT.nano facility has two such microscopes, which can be used to reveal the fine details of tiny structures.

The research was funded by the National Science Foundation, the Office of Naval Research, the Army Research Office, and the National Institute of Allergy and Infectious Disease.

Related links

ARCHIVE: Synthetic circuits can harvest light energy http://news.mit.edu/2017/synthetic-circuits-can-harvest-light-energy-solar-power-1113

ARCHIVE: Automating DNA origami opens door to many new uses http://news.mit.edu/2016/automating-dna-origami-opens-door-many-new-uses-0526

ARCHIVE: Computer model enables design of complex DNA shapes http://news.mit.edu/2014/computer-model-for-complex-dna-shapes-1203

Massachusetts Institute of Technology

Related Dna Articles:

In one direction or the other: That is how DNA is unwound
DNA is like a book, it needs to be opened to be read.
DNA is like everything else: it's not what you have, but how you use it
A new paradigm for reading out genetic information in DNA is described by Dr.
A new spin on DNA
For decades, researchers have chased ways to study biological machines.
From face to DNA: New method aims to improve match between DNA sample and face database
Predicting what someone's face looks like based on a DNA sample remains a hard nut to crack for science.
Self-healing DNA nanostructures
DNA assembled into nanostructures such as tubes and origami-inspired shapes could someday find applications ranging from DNA computers to nanomedicine.
DNA design that anyone can do
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.
DNA find
A Queensland University of Technology-led collaboration with University of Adelaide reveals that Australia's pint-sized banded hare-wallaby is the closest living relative of the giant short-faced kangaroos which roamed the continent for millions of years, but died out about 40,000 years ago.
DNA structure impacts rate and accuracy of DNA synthesis
DNA sequences with the potential to form unusual conformations, which are frequently associated with cancer and neurological diseases, can in fact slow down or speed up the DNA synthesis process and cause more or fewer sequencing errors.
Changes in mitochondrial DNA control how nuclear DNA mutations are expressed in cardiomyopathy
Differences in the DNA within the mitochondria, the energy-producing structures within cells, can determine the severity and progression of heart disease caused by a nuclear DNA mutation.
Switching DNA and RNA on and off
DNA and RNA are naturally polarised molecules. Scientists believe that these molecules have an in-built polarity that can be reoriented or reversed fully or in part under an electric field.
More Dna News and Dna Current Events

Top Science Podcasts

We have hand picked the top science podcasts of 2019.
Now Playing: TED Radio Hour

Risk
Why do we revere risk-takers, even when their actions terrify us? Why are some better at taking risks than others? This hour, TED speakers explore the alluring, dangerous, and calculated sides of risk. Guests include professional rock climber Alex Honnold, economist Mariana Mazzucato, psychology researcher Kashfia Rahman, structural engineer and bridge designer Ian Firth, and risk intelligence expert Dylan Evans.
Now Playing: Science for the People

#541 Wayfinding
These days when we want to know where we are or how to get where we want to go, most of us will pull out a smart phone with a built-in GPS and map app. Some of us old timers might still use an old school paper map from time to time. But we didn't always used to lean so heavily on maps and technology, and in some remote places of the world some people still navigate and wayfind their way without the aid of these tools... and in some cases do better without them. This week, host Rachelle Saunders...
Now Playing: Radiolab

Dolly Parton's America: Neon Moss
Today on Radiolab, we're bringing you the fourth episode of Jad's special series, Dolly Parton's America. In this episode, Jad goes back up the mountain to visit Dolly's actual Tennessee mountain home, where she tells stories about her first trips out of the holler. Back on the mountaintop, standing under the rain by the Little Pigeon River, the trip triggers memories of Jad's first visit to his father's childhood home, and opens the gateway to dizzying stories of music and migration. Support Radiolab today at Radiolab.org/donate.