NSF Award
2312215
DNA nanotechnology aims to use DNA as a scaffolding material to assemble engineered structures at the molecular scale, with nanometer precision. While most DNA nanotechnology molecules make use of DNA in the naturally occurring right-handed form known as D-DNA, an alternative uses chemically synthesized “left-handed” DNA, known as L-DNA, enabling the creation of DNA objects that twist in the opposite direction. A practical advantage of L-DNA molecules is that they resist degradation by enzymes in biological environments, which have evolved to recognize D-DNA specifically. On the other hand, while D-DNA molecules are more prone to degradation, they can interface directly with biological nucleic acids such as DNA and RNA. Therefore, it may be advantageous to combine the two forms of DNA into a single chiral hybrid, or “heterochiral”, form of DNA. This project will contribute to advancing the state of the art in DNA nanotechnology by studying the structure and function of such heterochiral nanostructures and by using this knowledge to engineer novel functional DNA nanodevices. Computational models and experimental results will be disseminated to the broader research community, and this project will train graduate and undergraduate students, including those from underrepresented groups, in interdisciplinary research skills. Public outreach efforts will be carried out in conjunction with local partner institutions.<br/><br/>At the molecular level, a heterochiral DNA junction may have drastic effects on the stability and structure of a larger DNA nanotechnology object. This project will use molecular dynamics simulations to study the structures of heterochiral DNA double helices in the region of a chiral crossover, currently a poorly understood aspect of DNA structure given the novelty of these molecules. The results of these simulations will be used to make predictions about the behavior of heterochiral DNA, which will be validated experimentally. The project will produce engineering design rules for DNA nanostructures that combine D-DNA and L-DNA components, with the broad goal of controlling degradation pathways for these nanostructures in biological environments. These will be verified by studying the behavior of these components in model biological fluids that mimic conditions in vivo. The results obtained will enhance knowledge of DNA structure with regard to the interactions between different chiralities of DNA and will lead the way to practical applications of heterochiral DNA as a functional biomaterial for biomedical applications.<br/><br/>This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.
