Elisa Schrader Echeverri
BME PhD Proposal Presentation

Date: 2024-06-13
Time: 2:00pm - 4:00pm
Location / Meeting Link: HSRB II N600 / https://emory.zoom.us/j/95198657704

Committee Members:
James E. Dahlman, PhD (Advisor); Wilbur A. Lam, MD, PhD; Felipe Quiroz, PhD, Hanjoong Jo, PhD; Brandon Dixon, PhD

Title: Design and formulation optimization of Lipid Nanoparticles (LNPs) carrying mRNA to the pancreas and the heart

Although lipid nanoparticles (LNPs) have clearly become a clinically significant way of delivering RNA therapies as seen with Alnylam’s ONPATTRO® used for genetic liver diseases and through Moderna’s SPIKEVAX® and Pfizer-BioNTech’s COMIRNATY®, used for vaccination against COVID-19, their presence in the clinic is still very limited, with much room for development. One of the biggest challenges is finding systemic LNPs that can target non-liver organs such as the pancreas and the heart. These two organs are examples that have historically been hard to target and that are related to diseases that continue to be directly correlated to increasing mortality rates. Through my work, I propose to 1) use previously established screening systems to identify potential pancreas targeting LNPs and 2) explore different formulation methods and parameters to further optimize a previously identified heart-delivering particle and apply it to a clinically relevant atherosclerotic disease model. To do this I will apply different quantification methods such as flow cytometry, immunofluorescence histology and single-cell spatial imaging systems. This work will help build a basis for better understanding how LNP composition and formulation process can affect their performance in vivo to further streamline their clinical relevance growth.