Can we control gene transcription and transfection using DNA origami?
Complex chemical and spatial coordination leads to the processing of information from a DNA to RNA and finally to a protein inside living cells. To leverage the central dogma of life that drives this information processing, external nucleic acid is often introduced into living cells in the form of therapeutic interventions to reprogram them. The delivery of external nucleic acid is challenged due to the limited options of delivery carriers - the gold standard being viral capsules or lipid-based nanoparticles. The overarching goal of this work is to develop a new methodology of delivering nucleic acid interventions to the cell using the architectural abilities of DNA nanotechnology. Our approach is to build DNA nanoparticles that help elucidate the mechanisms of transcription at the DNA-enzyme molecular level and transfection at the cellular interface. We use single cell manipulation, multi-step Förster resonance energy transfer, and nucleic acid chemistry to achieve these goals.