Afsane Radmand 

BioE PhD proposal  

October 3rd, 2022, 11 AM 

    Link: https://gatech.zoom.us/j/93835347627?pwd=TjNaR0pGc1JUeEVra2tBcHZLNnJQQT09 

Advisor:  

James E. Dahlman, Ph.D. Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University 

Committee Members: 

Philip J. Santangelo, Ph.D. 

Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University 

Julie A. Champion, Ph.D. 

Department of Chemical and Biomolecular Engineering, Georgia Institute of Technology 

Wilber Lam, Ph.D.  

Department of Biomedical Engineering, Georgia Institute of Technology and Emory University 

Brandon Dixon, Ph.D. 

Department 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 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 still remains needs to rationally design next-generation LNP formulations for systemic non-liver delivery and for vaccination against other malignant diseases 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 lipids in LNP formulation on systemic in vivo non-liver tropism, and (iii) develop a mRNA-based LNP vaccine for RSV. This work will establish the foundation towards two crucial objectives: (1) exploiting lipid nanoparticle design rules for systemic non-liver delivery of nucleic acid-based therapies (2) determining factors for LNP mRNA-based vaccine immunogenicity which will allow for taking a leap towards developing clinically relevant nucleic acid-based vaccines.