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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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David Wolfson
BMED PhD Proposal Presentation
Date: Tuesday, March 24, 2020
Time: 2:00 PM
Location: HSRB E260
Advisor:
Hee Cheol Cho, PhD (Emory University)
Committee:
Philip Santangelo, PhD (Georgia Tech)
Sung Jin Park, PhD (Emory University)
Chunhui Xu, PhD (Emory University)
Jennifer Kwong, PhD (Emory University)
Use of modified mRNA as a gene delivery tool for modulating cardiac electrophysiology
Current somatic gene transfer techniques in cardiomyocytes largely rely on recombinant viral vectors. For instance adenoviral delivery of the transcription factor, TBX18, has proven successful in converting ventricular myocytes to pacemaker cells. Though effective, viral vectors may elicit adverse/catastrophic immune reaction. Conversely, in vitro transcribed, modified mRNA (IVT mRNA) offers a versatile, easy-to-make gene transfer modality with a lower immunogenic profile. Thus, this project seeks to test the functional efficacy of somatic gene transfer of IVT mRNAs in cardiomyocytes for modulating their electrophysiological phenotype. IVT mRNA will be generated from codon-optimized DNA templates, incorporating modified nucleotides for enhanced stability. In order to visualize functional and successful transfection, fluorescent and bioluminescent reporter-encoded IVT mRNAs will be used as a readout for success. In terms of electrophysiological modulation, TBX18-encoded IVT mRNA will be used to test for known phenotypic changes both in vitro and in vivo. If successful, this will be the first study making use of IVT mRNA for cardiac delivery of TBX18 as a gene therapy for cardiac pacing. Compared to traditional viral vectors, IVT mRNA will mitigate concerns of potential off-target and inflammatory effects, thus advancing the clinical translation of electrophysiological therapies, such as biological pacemakers.
