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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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Melissa Lokugamage
BME PhD Proposal Presentation
Date: May 28th, 2020
Time: 12:00 PM
Location: https://bluejeans.com/195074330
Committee Members:
James E. Dahlman, Ph.D. (Advisor)
Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University
Philip J. Santangelo, Ph.D.
Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University
Edward Botchwey, Ph.D.
Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University
Wilbur Lam, M.D., Ph.D.
Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University
Eric Sorscher, M.D.
Department of Pediatrics, Emory University School of Medicine
Title: Utilizing high-throughput in vivo nanoparticle screens to improve drug delivery
Abstract: Lipid-based nanoparticles (LNPs) have emerged as a leading delivery system for nucleic acid therapies and have been used for clinically relevant delivery of RNA-based drugs. Nucleic acids drugs, such as small RNAs, can be utilized to modulate the expression of any gene, making it a powerful tool. While these advances are exciting, systemic delivery of LNP therapies to non-hepatocytes in vivo remains a challenge. Despite complex in vivo barriers, nanoparticles are typical screened in vitro. We have shown that in vitro screening methods for nanoparticles do not recapitulate in vivo barriers. To accurately study LNP delivery, taking into account all of the barriers encountered in vivo, and to improve the capacity of RNA therapeutics, we sought to develop a new approach for in vivo nanoparticle discovery, facilitating RNA-based therapies to treat genetic diseases in patients. In this proposal, we sought to designed and utilize improved DNA barcoding systems to simultaneously test hundreds of LNPs in vivo. First, we create novel LNP screening systems to quantify absolute delivery of nucleic acids. Second, we use our screening systems to test hundreds of unique LNPs in vivo; we identify novel LNP components and traits that shift delivery away from the liver hepatocytes. Third, we test how alterations to endocytosis genes effected nanoparticle delivery in a cell-type dependent manner. Fourth, we examine the effects of inflammation on delivery. Several disease states include TLR4-mediated inflammatory signaling; our data suggests that TLR4-mediated inflammation inhibits LNP-mediated mRNA delivery. Taken together, this proposal allows us to improve and study LNP delivery to enable gene therapies.
