The new ability to self-assembly of DNA nanostructures eliminates the need for extreme heating and controlled cooling

The University of Albany Researchers at RNA Institute is pioneering new methods for designing and assembling DNA nanostructures, increasing the possibilities for real-world applications in medicine, materials science and data storage.

Their latest discoveries demonstrate the new ability to assemble these structures without the need for extreme heat and controlled cooling. They also demonstrate the success of assembling unconventional “buffering agent” substances containing nickel. Published in the journal Science Advances, these developments unlock new possibilities for DNA nanotechnology.

DNA is most commonly recognized for its role in the conservation of genetic information. Easy to manipulate DNA is also an excellent material for building nanoscale objects. By “programming” the base pairs that make up DNA molecules, scientists can create precise structures as small as a few nanometers that can be designed into shapes in complex architectures.

These structures use small scales and custom designs to place things like biomolecules, cells, nanoparticles very accurately, and can be used using biomedical (drug delivery, therapy, diagnostic tools, etc.) and material design applications.

Creating these structures often requires heating the DNA strands, usually cooled with a special buffer solution containing magnesium ions. However, the need for accurate temperature control limits the possibilities for practical applications, and DNA nanostructures assembled in magnesium can pose challenges including structural instability in the biological environment.

To address these issues, the Ualbany team is exploring ways to assemble DNA nanostructures at medium temperatures and assemble various metal ion solutions that lead to more stable nanostructures.

“Usually, the component DNA strands are mixed with a buffer solution to assemble the DNA nanostructures, and the solution is heated to high temperatures (194-203 degrees Fahrenheit) and cooled to low temperatures.”

“This new study shows that DNA nanostructures can be assembled at isotherms, i.e., at a constant medium temperature of about 68 degrees Fahrenheit (room temperature) or 98.6 degrees Fahrenheit (body temperature) at about 68 degrees Fahrenheit (body temperature). These structures at constant temperatures for applications in biological and materials science.”

Many DNA nanostructure applications involve attaching temperature-sensitive proteins (such as enzymes and antibodies) to nanostructures. By assembling DNA nanostructures at medium temperatures, these delicate biological components can be used to easily construct DNA nanodevices for drug delivery and diagnostic purposes.

“Importantly, this work brings us closer to imagining how these nanostructures can actually be created and used in the human body for targeted drug delivery or precision diagnosis,” Chandrasekaran said. “While we still have a long way to go before this is possible, demonstrating DNA nanostructure assembly at body temperature is a promising step.”

In previous studies, the Ualbany team used calcium, barium, sodium, potassium and lithium in their DNA nanostructure assemblies using a high temperature approach. In this study, they added nickel and strontium to their list, but the important difference is that these substances can be used to construct DNA nanostructures in the room and body temperature.

Assemble DNA nanostructures without the use of magnesium, and at moderate temperatures it increases the potential utility of the structure in a variety of applications. They also showed that DNA nanostructures created using this method have no adverse effects on cell viability or immune responses, indicating potential use in biological applications.

“Our ongoing research aims to optimize nanostructure assemblies of various metal ions and test the bioexistence of these structures for a variety of potential future applications,” says Chandrasekaran. “We hope that through innovative approaches to the design and stabilization of DNA nanostructures, these advances in nanotechnology will help pave the way for new solutions to complex challenges in medicine and beyond.”

This was a collaboration with Chandra Sekaran Lab. Contributors include Post-Doctor Associate Balath Raj Madanagopal, Research Associates Arlyn Rodriguez and Dr. Akul Patel. Students Hannah Talbot and collaborators Andrew Bergland, Sweta Vangavety and Ken Halvlusen.