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

Synthetic mRNA;PET imaging;HIV;Female reproductive tract

Lindsay, Kevin E. ; Santangelo, Philip J. Biomedical Engineering (Joint GT/Emory Department) Villinger, Francois Lam, Wilbur Hunter, Eric Roy, Krishnendu Dixon, Brandon ; Santangelo, Philip J.

University:Georgia Institute of Technology

Department:Biomedical Engineering (Joint GT/Emory Department)

关键词: Synthetic mRNA;    PET imaging;    HIV;    Female reproductive tract;   

Others  :  https://smartech.gatech.edu/bitstream/1853/61677/1/LINDSAY-DISSERTATION-2018.pdf

美国|英语

来源: SMARTech Repository

【 摘 要 】

Delivering molecular immunotherapies to the necessary organs is a frequent bottleneck in translating drugs to the clinic. We directly associate adjuvants to naked mRNA in an orthogonal fashion so that sufficient and directed immune responses are elicited against the expressed antigen. We then 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 in sheep and non-human primate animal models.