Kevin Lindsay

Ph.D. Thesis Defense Presentation

Date: Tuesday, July 24, 2018 

Time: 9:00 am
Location: UAW 3115 (McIntire)

Advisor: Phil Santangelo, Ph.D. 

Committee:
Brandon Dixon, Ph.D.
Krish Roy, Ph.D. 
Wilbur Lam, MD, Ph.D. 
Eric Hunter, Ph.D.
Francois Villinger, DVM, Ph.D. 

Title: Orthogonal platforms to modulate, monitor, and deliver mRNA in vivo

Summary:

Delivering molecular immunotherapies to the necessary organs is a frequent bottleneck in translating drugs to the clinic. We demonstrate two non-invasive approaches - one focused on imaging and the other on mucosal delivery - that attempt to inform the discussion of mRNA delivery in large mammals. To aid in the rational design of mRNA vaccines, we developed a dual PET/near-IR based approach to non-invasively monitor mRNA trafficking longitudinally with high spatio-temporal resolution in non-human primates. This dual imaging modality approach has the potential to link systemic scale events with cellular level details. We use this PET/CT based approach to monitor mRNA trafficking after transfection of the female reproductive tract (FRT) epithelium. Using antibody modifications, we can generate robust levels of the HIV broadly neutralizing antibody PGT121 that reach neutralizing concentrations within hours and persist for weeks.