Liming Lian
BME PhD Proposal Presentation

Date: 2025-08-06
Time: 12:00 PM-1:00 PM
Location / Meeting Link: HSRB II N600, https://emory.zoom.us/j/97819777282

Committee Members:
Dahlman, James E., Ph.D. (Advisor) Kim, Hyejin, Ph.D. Allison, Kyle R., Ph.D. Salaita, Khalid, Ph.D. Finn, M.G, Ph.D.


Title: Development of lipid nanoparticles for respiratory-related disease treatments via different administration methods

Abstract:
Lipid nanoparticles (LNPs) have emerged as a clinically validated platform for nucleic acid delivery, with successful translation in FDA-approved COVID-19 vaccines (e.g., SPIKEVAX by Moderna and COMIRNATY by Pfizer/BioNTech). However, most clinically available LNPs are optimized for hepatic delivery following intravenous administration, limiting their utility for other organs and diseases. Respiratory diseases represent a significant global health burden, including infectious diseases like influenza and respiratory syncytial virus (RSV), as well as rare autoimmune conditions such as pulmonary alveolar proteinosis (aPAP). Each of these diseases affects distinct regions of the respiratory tract and therefore requires tailored LNP delivery strategies. In this work, I propose to develop LNPs optimized for treating respiratory diseases through three distinct administration routes. First, I aim to engineer a nebulized LNP for mRNA delivery to the lungs for aPAP, a disease characterized by alveolar macrophage dysfunction. Second, I develop intranasal LNPs for targeted delivery to the nasal cavity and nasal-associated lymphoid tissue (NALT), with a focus on prophylactic or therapeutic treatment of influenza A virus (IAV) infection. Third, I designed an LNP-based mRNA vaccine for RSV delivered by intramuscular injection, with the goal of achieving potent immunogenicity and protective efficacy. Collectively, this work highlights the versatility of LNPs and demonstrates that route-specific formulation can enable targeted mRNA delivery to multiple compartments of the respiratory tract. These findings may accelerate the development of next-generation RNA therapies for both localized and systemic respiratory diseases.