Development of a Structural Nucleic Acid Delivery Vector Technology

Abstract

The delivery of biomacromolecules such as proteins and nucleic acids to specific cells inside the body remains a critical challenge in contemporary biomedical research. Delivery technologies to accomplish this are ideally safe, effective, versatile, and scalable, but the current commercial technologies often fall short of these characteristics. Nucleic acid nanoparticles, which are computationally-designed nanostructured assemblies of nucleic acid, represent a promising foundational technology to utilize in delivery applications. Here, I present several advancements towards developing a delivery platform designed on nucleic acid nanoparticles. After introducing the current challenges in delivery and the current commercial technologies, I detail why nucleic acid nanoparticles offer promise as components of a delivery technology. Then, I describe my thesis work on evaluating the safety of nucleic acid nanoparticles in pre-clinical animal models, on their fabrication with a focus on integrating new chemistries and characterization techniques, and on a proof-of-concept demonstration in using nucleic acid nanoparticles to deliver viral antigens in a vaccine formulation. Finally, I summarize where I think the state of the technology is today, where its potential could reach, and what the path to reach that potential is.