PhD Proposal by Melissa Lokugamage

Event Details
  • Date/Time:
    • Thursday May 28, 2020
      12:00 pm - 2:00 pm
  • Location: REMOTE
  • Phone:
  • URL: BlueJeans Link
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Summaries

Summary Sentence: Utilizing high-throughput in vivo nanoparticle screens to improve drug delivery

Full Summary: No summary paragraph submitted.

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.

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In Campus Calendar
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Graduate Studies

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Faculty/Staff, Public, Graduate students, Undergraduate students
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Other/Miscellaneous
Keywords
Phd proposal
Status
  • Created By: Tatianna Richardson
  • Workflow Status: Published
  • Created On: May 18, 2020 - 1:51pm
  • Last Updated: May 18, 2020 - 1:51pm