DNA bricks enable self-assembly of 3D nanostructures from 10,000 unique components, advancing DNA nanotech from Mega to GigaDalton scale
DNA, present in almost every cell, is increasingly being used as a building material to construct tiny, but sophisticated structures such as autonomous ‘DNA walkers’ that can move along a microparticle surface, fluorescent labels for diagnostic applications, ‘DNA boxes’ that serve as smart drug-delivery vehicles programmed to open up at disease sites to release their therapeutic content, or programmable factories for nanoparticles of defined sizes and shapes for new optical and electronic applications.
This video illustrates how 10,000 next-generation DNA bricks technology is used to self-assemble the complex cavity with the shape of a teddy bear. Credit: Molgraphics
To accommodate these functions, researchers at Harvard’s Wyss Institute for Biologically Inspired Engineering and around the world have developed ways that allow DNA strands to self-assemble into increasingly complex 3D structures such as scaffolded DNA origamis. DNA origamis, however, are limited in their sizes because they rely on the availability of scaffold strands that can be difficult to manufacture and manipulate. In 2012, Peng Yin and his team at the Wyss Institute presented an alternative method in Nature (2D) and Science (3D) that is based on DNA ‘bricks’, which do not use a scaffold but rather are able to connect like interlocking Lego® bricks and thereby self-assemble into origami-sized structures with prescribed shapes.
As reported in Nature, the team leapfrogged their technology by two orders of magnitude, enabling next-generation DNA bricks to self-assemble into three-dimensional nanostructures that are 100 times more complex than those created with existing methods. DNA origami and first generation DNA bricks self-assemble from hundreds of unique components to produce nanostructures on the MegaDalton scale, whereas the new DNA bricks approach allows 10,000 components to self-assemble into GigaDalton-sized structures (1 GigaDalton equals 1000 MegaDaltons or 1 billion Daltons). The study provides user-friendly computational tools to design DNA nanostructures with complex cavities (and possibly surfaces) that have the potential to serve as building components in numerous nanotechnological applications in medicine and engineering.
“The principle and promising capabilities of our first-generation DNA bricks led us to ask whether we can enhance the system to attain significantly more complex nanostructures with much higher yields in one-pot assembly reactions. Here we managed to do all this. We worked out an easily accessible practical platform that allows researchers with very different interests and applications in mind to create a molecular canvas with 10,000 bricks and use it to build nanostructures with unprecedented complexities and potential,” said corresponding author Yin, Ph.D., who is a Wyss Institute Core Faculty member, co-leader of the Institute’s Molecular Robotics Initiative, and Professor of Systems Biology at Harvard Medical School.
DNA brick technology is based on the stable and highly programmable nature of DNA. A single DNA brick is a short strand of synthetic DNA made up of a pre-defined sequence of the four universal nucleotide bases: adenine (A), cytosine (C), guanine (G), and thymine (T). The Wyss Institute’s researchers create large 3D nanostructures by mixing various bricks, each carrying its own unique sequence of nucleotides that is designed to fit and bind to a complimentary domain of nucleotide bases in another brick so that they can self-assemble. In the technology’s new version, by varying the length of individual binding domains within the bricks, the team ended up with a substantially increased diversity among possible bricks that, in addition, bind much stronger to each other. The study also developed a user-friendly computer softwareso designers can simply input a required 3D shape and automatically receive a list of DNA brick sequences that can be synthesized and used to form the desired structure.
“We demonstrated the capabilities of our technology by constructing massive cuboids containing up to 30,000 bricks and showed a few exemplary shapes that can be built from subsets of those bricks. It is remarkable that the bricks were able to distinguish between tens of thousands of potential partners to find their correct neighbors, and it was exciting to see that the DNA bricks technique could be used to form rather complex cavities such as a teddy bear, the word ‘LOVE’ or a Möbius strip, amongst many others, ” said first author Luvena Ong, Ph.D., a former Graduate Student in Yin’s laboratory and now a Research Investigator at Bristol-Myers Squibb.
Yin’s team collaborated with researchers at the National Center for Scientific Research (CNRS) and the French National Institute of Health and Medical Research (INSERM) in Montpellier, France and the Max Planck Institute of Biochemistry in Munich, Germany to deploy a collection of state-of-the-art microscopy methods to visualize the designed cavities in 3D cuboids. “Cavity structures composed of DNA bricks are of much interest as they offer the possibility to design nano-containers in which biomolecules like proteins can be place in very defined arrangements to study their interactions and leverage their activities,” said co-corresponding author Yonggang Ke, Ph.D., who developed the first DNA brick platform with Yin as a Postdoctoral Fellow at the Wyss Institute, and is now Assistant Professor at the Georgia Institute of Technology and Emory University. Ke, working together with his Graduate Student Pengfei Wang, was instrumental in advancing the technology to its new version. “By adding functional moieties to DNA bricks that can carry out assembly and enzymatic processes, they can be converted into powerful tools for commercial and biomedical nanofabrication processes on a new scale,” said Ke. The researchers believe that, in the future, the method could also be used to generate large nanostructures with sculpted and application-specific outer surfaces.
“The way the multifaceted DNA bricks technology is evolving shows how the Wyss Institute’s Molecular Robotics Initiative can reach deep into the field of DNA nanotechnology to enable new approaches that could solve many real world problems,” said Wyss Institute Founding Director Donald Ingber, M.D., Ph.D., who is also the Judah Folkman Professor of Vascular Biology at HMS and the Vascular Biology Program at Boston Children’s Hospital, as well as Professor of Bioengineering at SEAS.
Learn more: A 100-fold leap to GigaDalton DNA nanotech
The Latest on: DNA nanotechnology
[google_news title=”” keyword=”DNA nanotechnology” num_posts=”10″ blurb_length=”0″ show_thumb=”left”]- Twist Bioscience Launches Multiplexed Gene Fragments to Enable High-throughput Screening Applicationson May 13, 2024 at 4:59 am
Twist Bioscience Corporation (NASDAQ: TWST), a company enabling customers to succeed through its offering of high-quality synthetic DNA using its silicon platform, today announced the launch of Twist ...
- Best DNA Test for 2024on May 3, 2024 at 4:01 am
CNET’s expert staff reviews and rates dozens of new products and services each month, building on more than a quarter century of expertise. Open up even more of your world with the best at-home ...
- Imec.xpand raises $320M for fund to invest in semiconductors and nanotechnologyon May 2, 2024 at 7:04 am
Imec.xpand, a chip and nanotech-focused venture capital fund, announced the launch of a new $320 million fund today.
- Dynamic DNA structures and the formation of memoryon April 30, 2024 at 5:00 pm
The G4-DNA structure can therefore be involved in both the enhanced and impairment of transcription in active neurons, based on their activity, to enable different memory states. This mechanism ...
- Plants detected in ancient Mayan ‘ballcourts’ point to a sacred spoton April 29, 2024 at 11:37 am
Advances in environmental DNA sequencing show that these areas were for more than just for recreation. By Laura Baisas | Published Apr 29, 2024 2:37 PM EDT A decorative ring made from carved stone is ...
- Scientists construct sophisticated synthetic system using self-replicating nanostructureson April 29, 2024 at 7:03 am
A research team led by the late Professor Liang Haojun from the Hefei National Laboratory for Physical Sciences at the Microscale of University of Science and Technology of China (USTC) has developed ...
- Neuroscientists Discover Shapeshifting DNA Controls Memory Formationon April 17, 2024 at 9:16 am
Neuroscientists have uncovered a new mechanism for memory formation, and it involves changes in the structure of your DNA. If you were asked to picture a molecule of DNA, chances are you would ...
- Structural DNA Nanotechnologyon March 26, 2024 at 3:20 am
Written by the founder of the field, this is the first text of its kind, providing a definitive introduction to structural DNA nanotechnology. Readers will learn everything there is to know about the ...
- DNA Nanotechnology Market worth $24.3 Bn by 2031 - Exclusive Report by InsightAce Analytic Pvt. Ltd.on March 20, 2024 at 11:53 pm
Ltd. announces the release of a market assessment report on the "Global DNA Nanotechnology Market – By Type (Structural DNA Nanotechnology (Extended Lattices, Discrete Structures, Template ...
- Understanding Bottom-up Nanotechnology and Its Impact on Future Innovationson February 25, 2024 at 3:58 am
Molecular assembly represents a more engineered approach to nanotechnology, holding the promise of fabricating advanced devices with functionalities designed from the ground up. Innovative ...
via Google News and Bing News