Programmable biomolecular integration and dynamic behavior of DNA-based systems for development of biomedical nano-devices

Abstract

Departing from the traditional role as a carrier of genetic information, DNA has emerged as an engineering material for construction of nano-devices. The advances in the field of DNA nanotechnology have enabled design and synthesis of DNA nanostructures of arbitrary shapes and manipulation of the nanostructures' conformations in a programmable way. DNA-based systems offer potential applications in medicine by manipulating the biological components and processes that occur at the nanometer scale. To accelerate the translation of DNA-based systems for medical applications, we identified some of the challenges that are hindering our ability to construct biomedical nano-devices and addressed these challenges through advances in both structural and dynamic DNA nanotechnology. First, we tested the stability of DNA nanostructures in biological environments to highlight the necessity of and path towards protection strategies for prolonged integrity of biomedical nano-devices. Then, we constructed a platform for robust 3D molecular integration using DNA origami technique and implemented the platform for a nanofactory capable of production of therapeutic RNA to overcome the challenges in RNA delivery. Moreover, we established a mechanism to drive DNA devices by changing temperature with prolonged dynamic behavior that was previously challenging to accomplish without special modification of DNA and/or equipment not readily available in a typical lab setting. Together, the progress made in this thesis bring us another step closer to realization of medical applications of DNA nanotechnology by focusing on the challenges in both structural and dynamic aspects of the technology.