(151c) De Novo design of Customizable Multiscale DNA Biosensing Platforms

The ability to program, template, and grow biomaterials from the bottom-up offers an avenue to build scalable biosensors and actuators that can perform complex biological tasks on multiple scales. DNA itself is a biocompatible material, making it the ideal “tool” for spatiotemporal resolution and molecular level control with the ability to branch 1-1000s nanometer regimes. Specifically, the de novo design of DNA nanostructures over the last 20 years has enabled the production of biological tools with dynamic assemblies, scale-up ability, tunable properties on the nanoscale, stimuli responsiveness and microenvironment control. We have yet to realize the full potential of these tools to understand many biological functions and overcome biomaterial design challenges. However, promising applications have shown the capture of viruses using microscale DNA origami shells, structures for drug delivery, and nanoscale robots for molecular transport. The interdisciplinary innovation within the field of DNA nanotechnology provides a promising approach to probe biological questions and spaces that are typically inaccessible. Such innovations in DNA nanotechnology will empower us to address many fundamental biosensing challenges in human health monitoring and disease progression.

I will introduce multiple DNA origami design tools that showcase my expertise with DNA assembly design and experimental fabrication. I will present how we can build dynamic nanostructures capable of precise motion on the nanoscale and assemble into higher orders on the microscale. Then, I will present recent advances in de novo design of DNA origami spheres that can encapsulate proteins and assemble in physiological conditions visualized with cryo-TEM. The ability to design a plethora of DNA nanostructures with different geometries on different scales allows us to push the boundaries on what type of biosensing tools we can fabricate and lets us define the future of the field.

Lastly, I will discuss the goal of my future research group using DNA as a material to build customized multiscale biosensing platforms that branch the nano to microscale. By realizing the full potential of DNA nanostructure design we can address challenges in maternal health and neurodegenerative disease progression. With this overarching goal of building customized biosensing platforms with DNA, the students and researchers in my group will be trained in de novo DNA nanotechnology design, nucleic acid chemistries, electron microscopy, and optical microscopy methods to become the next generation of interdisciplinary scientists.