The SARS-CoV-2 pandemic demonstrated the power and adaptability of mRNA therapeutics for treating infectious diseases and has generated significant interest in expanding this emergent treatment modality into innovative treatments for infectious and chronic diseases. Designing effective mRNA therapeutics inherently relies on understanding several dynamic molecular processes such as protein synthesis, trafficking, and the activity of a range of innate and adaptive immune cells.

Whilst our grasp of the molecular processes underpinning the efficacy of these therapeutics continues to evolve, for instance via the discovery and characterisation of new immune cell specific receptors and functions (1-3), the landscape of experimental techniques routinely employed to study the spatiotemporal dynamics of the immune system and the cellular responses to mRNA therapeutics frequently rely on two-dimensional ex-vivo analytical techniques.

This presentation will discuss recent advancements in employing PET tracers to investigate the spatiotemporal dynamics of mRNA immunisation. We will explore how PET-CT imaging can provide longitudinal insights into critical processes such as antigen synthesis, immune cell infiltration, lymphatic dissemination, and the activation of immune effector cells. Our findings demonstrate that PET-CT is a powerful tool for visualising and understanding the molecular events essential for effective immune responses, thereby enhancing our knowledge of how mRNA therapeutics function biologically.

Please email AMTAR Manager s.osborne@uq.edu.au to register for Zoom link.

References

[1]          Schramm, C. A.;  Moon, D.;  Peyton, L.;  Lima, N. S.;  Wake, C.;  Boswell, K. L.;  Henry, A. R.;  Laboune, F.;  Ambrozak, D.;  Darko, S. W.;  Teng, I. T.;  Foulds, K. E.;  Carfi, A.;  Edwards, D. K.;  Kwong, P. D.;  Koup, R. A.;  Seder, R. A.; Douek, D. C., Nature Communications, 14 (1), 7961 (2023).
[2]        Teijaro, J. R.; Farber, D. L., Nature Reviews Immunology, 21 (4), 195-197 (2021).
[3]          Li, C.;  Lee, A.;  Grigoryan, L.;  Arunachalam, P. S.;  Scott, M. K. D.;  Trisal, M.;  Wimmers, F.;  Sanyal, M.;  Weidenbacher, P. A.;  Feng, Y.;  Adamska, J. Z.;  Valore, E.;  Wang, Y.;  Verma, R.;  Reis, N.;  Dunham, D.;  O’Hara, R.;  Park, H.;  Luo, W.;  Gitlin, A. D.;  Kim, P.;  Khatri, P.;  Nadeau, K. C.; Pulendran, B., Nat. Immunol., 23 (4), 543-555 (2022).

Bio

Dr James Humphries is a Postdoctoral Research Fellow at the Centre for Advanced Imaging and Australian Institute for Bioengineering and Nanotechnology at The University of Queensland. James is a chemical biologist with a research focus on developing molecular imaging-based readouts for therapeutic efficacy. He has extensive experience in radiolabelling and quality assurance development for novel radiotheranostics, as well as in molecular imaging.

James’ research focuses on developing PET and SPECT based molecular imaging protocols that can longitudinally monitor immunologically derived responses to a range of therapeutics, including radiopharmaceuticals. Concurrently to this, he is interested in developing small animal oncology models that better replicate the manifestation of human disease, as this is a critical to developing therapies that are effective in humans.