Afsane Radmand

BioE Ph.D. Defense Presentation

Time and Date: 3:00 – 5:00 PM, Thursday, June 22, 2023

Location: HSRB II, 1750 Haygood Drive, Atlanta, GA 30322, N600 (6th floor)

Zoom Link: https://gatech.zoom.us/j/3841552206

Passcode: 123

Advisor:

James E. Dahlman, Ph.D. School of Biomedical engineering, Georgia Institute of Technology and Emory University

Committee Members: 

Philip J. Santangelo, Ph.D. School of Biomedical engineering, Georgia Institute of Technology and Emory University

Julie A. Champion, Ph.D. School of Chemical and Biomolecular Engineering, Georgia Institute of Technology

Wilbur Lam, Ph.D. School of Biomedical Engineering, Georgia Institute of Technology and Emory University

Brandon Dixon, Ph.D. School of Mechanical Engineering, Georgia Institute of Technology 

Next-generation lipid nanoparticle formulations for non-liver delivery of nucleic acid-based therapies and vaccines

The clinical application of lipid nanoparticles (LNPs) delivering RNA-therapies has advanced remarkably over the past few decades with the Food and Drug Administration (FDA) approval of ONPATTRO® in 2018 for treating a liver genetic disease following systemic administration and the most recent COVID-19 vaccines developed by Moderna Therapeutics Inc. and Pfizer-BioNTech in 2021. Despite the success of first-generation LNP-RNA therapies, there is still a need to rationally design next-generation LNP formulations for systemic non-liver mRNA delivery and for vaccination against other malignant viruses such as respiratory syncytial virus (RSV). In this work, we aimed to (i) identify helper lipid design rules and biological response for systemic lung mRNA delivery of LNPs, (ii) investigate the effect of cationic cholesterol in LNP formulation on systemic in vivo mRNA delivery, (iii) rationally enhance the immunogenicity of a developed mRNA-LNP RSV vaccine and (iv) develop a three-component stereopure mRNA-LNP vaccine to immunize against RSV. This work will establish the foundation towards achieving two crucial objectives: (1) exploiting lipid nanoparticle design rules for systemic non-liver delivery of RNA-based therapies and (2) determining factors for rational design of mRNA-LNP vaccines which will allow for taking a leap towards developing clinically relevant mRNA-based vaccines.