PhD Proposal by Jonathan Kirschman

Event Details
  • Date/Time:
    • Friday February 19, 2016
      12:00 pm - 2:00 pm
  • Location: Whitaker 2110
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Summaries

Summary Sentence: Characterization of in vitro transcribed mRNA for optimal expression in therapeutic applications

Full Summary: No summary paragraph submitted.

Committee:
Philip Santangelo, PhD (Advisor)
Loren Williams, PhD, GT-CHEM
Garrett Stanley, PhD, GT-BME
Krishnendu Roy, PhD, GT-BME
Thomas Barker, PhD, GT-BME

Characterization of in vitro transcribed mRNA for optimal expression in therapeutic applications

ABSTRACT
Messenger ribonucleic acid (mRNA) has recently come to focus as a versatile tool in molecular medicine for in vivo production of therapeutic proteins as well as viral antigens for vaccines. However, the cellular biophysics of this approach remains largely uncharacterized. This proposal will utilize a labeling approach, in which multiply-labeled tetravalent RNA imaging probes (MTRIPs) are hybridized to the 3' untranslated region (UTR) of in vitrotranscribed (IVT) mRNA prior to delivery into target cells, which enables dynamic visualization of extrinsic mRNA in live and fixed cells as well as tissue with single RNA sensitivity. Labeled mRNA in conjunction with assays for protein expression, RNA-protein interactions, intracellular localization, and innate immune activation will be used to identify key factors limiting expression. mRNA will be rationally designed using these metrics through incorporation of chemically modified nucleotides, different UTRs, and co-delivery with small molecules. This proposal aims to demonstrate effectiveness of this approach in vivo for expression of light-sensitive ion channels (opsins) in neurons used to study dynamic encoding of sensory information in the brain. In contrast to lenti- or adeno-associated viral vectors currently used, IVT mRNA allows for faster expression and reduced safety concerns which is beneficial for therapeutics.

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Keywords
PhD proposal defense
Status
  • Created By: Jacquelyn Strickland
  • Workflow Status: Published
  • Created On: Feb 5, 2016 - 10:40am
  • Last Updated: Oct 7, 2016 - 10:16pm