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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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Jared Beyersdorf
BME PhD Thesis Proposal Presentation
Date: February 16th
Time: 4:00 – 5:30 pm (EST)
Link: https://bluejeans.com/4450273439
Advisor:
Philip Santangelo, PhD
BME, Georgia Institute of Technology
Committee Members:
Krishnendu Roy, PhD
BME, Georgia Institute of Technology
Wilbur Lam, MD/PhD
BME, Georgia Institute of Technology
Department of Pediatrics, Emory University
James Dahlman, PhD
BME, Georgia Institute of Technology
Joseph Schoeniger, MD/PhD
Department of Systems Biology, Sandia National Laboratories
Title: Development of an mRNA-based Prophylactic for Protection Against Nerve Agent Toxicity
Abstract:
Nerve agents are toxic compounds that rapidly lead to cholinergic crisis in humans, leaving little time for medical intervention to prevent death. To overcome limitations with current medical interventions, protein bioscavengers of nerve agents, such as butyrylcholinesterase (BChE), have been developed. BChE circulates naturally in human plasma and binds to nerve agents before they can reach nerve synapses and induce toxicity. However, natural levels are too low to provide protection. Recombinant BChE has been shown to be effective in animals and safe in Phase I clinical trials, but exceedingly high doses must be administered, which are expensive and difficult to manufacture. As an alternative, we will develop mRNA-based strategies to prophylactically overexpress BChE for nerve agent protection. This proposal aims to 1) develop direct mRNA and gene activation approaches to maximize the secretion of functional BCHE protein in human in vitro systems and mouse models, 2) characterize LNP formulations for RNA loading and patterns of transfection in vivo, and 3) utilize an RNA-based prophylactic to protect mice from lethal nerve agent intoxication. By completing these aims, we will provide the first mRNA-based demonstration of nerve agent protection and improve current understanding of mRNA-based protein therapies.
