Investigating and Manipulating Cells in Low Oxygen Environments Using Lipid Nanoparticles

ABSTRACT Low Oxygen Environments (LOEs) are a common characteristic of numerous physiologically relevant conditions in many different locations in the body. Accordingly, understanding how LOEs impact the cellular response to technologies that can investigate and manipulate cells is an essential area of fundamental research that can lay the foundation for advancing health. Recently, lipid nanoparticles (LNPs) have emerged as promising technologies that can investigate and manipulate cells using messenger RNA (mRNA). Studies investigating the impact of LOE on mRNA LNP are currently limited, and addressing this key gap in our knowledge will be essential for understanding how to best investigate and manipulate cells in LOE using mRNA LNPs. Here, we will address this key gap in knowledge by studying two overarching Research Areas – Mechanism (Research Area 1) and Tool Development (Research Area 2). In Mechanism, we will perform comparative analyses exploring how various states of LOE impact the cellular uptake mechanisms of mRNA LNPs across different cell types, mRNA sequences, and LNP types. In Tool Development, we will develop Low Oxygen Environment Nanoparticles (LOENRs), a novel class of tools for better investigating and manipulating cells under LOE. This research will be performed in my laboratory at UNC, an environment that strives to train the next generation of scientific leaders in a diverse and inclusive environment. In undertaking this approach, we hope our research will provide key fundamental insights about how cells respond to LOE, a common characteristic of physiologically relevant conditions that arise in many different locations in the body.