Elisa Schrader Echeverri
BME PhD Defense Presentation
Date: 2024-11-20
Time: 1:00pm - 3:00pm
Location / Meeting Link: HSRBII N600, https://emory.zoom.us/j/95396634296
Committee Members:
James Dahlman, PhD (advisor) Wilbur Lam (MD/PhD) Felipe Quiroz (PhD) Hanjoong Jo (PhD) Brandon Dixon (PhD)
Title: Design and Formulation Optimization of Lipid Nanoparticles Carrying mRNA to the Heart and the Pancreas
Abstract:
Nucleic acid therapies are a field that has slowly been developing over time as a method that helps target the source cause of many diseases and provide a more natural and lasting treatment. In order for these therapies to be effective, they need to overcome various barriers such as an organism’s immune system, the cellular membrane and the lysosome process that cells go through to get rid of foreign molecules. Lipid nanoparticles (LNPs) are one of the vehicle types that have been developed to overcome some of these barriers. However, their full potential to target non-liver, organ-specific types of diseases while minimizing their off-target effects to the liver and other organs is yet to be fully explored. Additionally, another challenge is understanding how scaling up their production can influence how they perform in the clinic. The pancreas and the heart are examples of organs known for their hard-to-treat diseases and therefore a potential appealing opportunity for RNA-LNP drugs. The data presented here demonstrates how combining already existing LNP screening systems and testing production conditions can affect how these particles behave in vivo. By testing different chemical and mechanical factors, we were able to identify patterns that affect the performance of LNPs when targeting the heart and the pancreas. This works helps bridge the gap between LNPs that are effective at the benchside but are unable to make it to the clinic due to differences in formulation and preparation. Getting a better understanding of all the different factors that can affect LNP behavior in vivo can help direct earlier research and hopefully accelerate the work of further LNP-nucleic acid therapies for diseases such as atherosclerosis, pancreatic cancer or diabetes mellitus.