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There is now a CONTENT FREEZE for Mercury while we switch to a new platform. It began on Friday, March 10 at 6pm and will end on Wednesday, March 15 at noon. No new content can be created during this time, but all material in the system as of the beginning of the freeze will be migrated to the new platform, including users and groups. Functionally the new site is identical to the old one. webteam@gatech.edu
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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.
