Stabilization of mRNA-LNP vaccines and therapeutics
|Interdisciplinary Areas:||Engineering-Medicine, Future Manufacturing, Micro-, Nano-, and Quantum Engineering, Others
mRNA vaccines are a promising approach to preventing infectious disease and treating some forms of cancer. The instability of mRNA is a critical weakness of this new drug class, however. To ensure adequate stability during shipping and storage, pharmaceutical companies are pursuing lyophilization as an alternative to ultracold storage. There is a lack of fundamental information on the mechanisms of chemical and physical degradation of mRNA in the solid state under formulation relevant conditions, however. Such information could support and accelerate the development of lyophilized mRNA products if it were available.
The Gilbreth Fellow will begin to address this knowledge gap in this project. The research program will include the development of analytical methods for mRNA in solid and semi-solid media, studies of mRNA chemical degradation, and assessment of the effects of drying process parameters on the physical stability and morphology of lipid nanoparticles (LNP). The Gilbreth Fellow’s research will be tailored to his/her aptitudes and interests. The project involves the Purdue College of Engineering, the Purdue College of Pharmacy, and Pfizer. An optional international experience at the National Institute for Bioprocessing Research and Training in Dublin, Ireland, will be available to an interested Fellow.
PhD or equivalent degree in chemical or biomedical engineering, pharmaceutical science, or a closely related discipline. Preferably research experience in RNA delivery, nanoparticle or LNP design and formulation, experimental knowledge and skills in bioanalytical characterization.
Alina Alexeenko, AAE & CHE, College of Engineering
Elizabeth Topp, IPPH, College of Pharmacy
Serguei Tchessalov, Research Fellow, Pfizer
- Solid-state hydrogen deuterium exchange mass spectrometry: Correlation of deuterium uptake and long-term stability of lyophilized monoclonal antibody formulations. S. M. Balakrishnan, I. D. Zarraga, L. Kumar, B. Walters, P. Goldbach, E. M. Topp and A. Allmendinger. Molecular Pharmaceutics, 15/1: 1-11, 2018.
- Effects of secondary structure on solid-state hydrogen-deuterium exchange in model α-helix and β-sheet peptides. R. Kammari and E. M. Topp. Molecular Pharmaceutics, 17/9: 3501-3512, 2020.
- A new method for RF-assisted lyophilization based on statistical electromagnetics. Ahmed Abdelraheem, Michael D. Sinanis, Rishabh Tukra, Petr Kazarin, Alina Alexeenko, Elizabeth Topp, Dimitrios Peroulis, in preparation.
- Future directions: Lyophilization technology roadmap to 2025 and beyond. Alina Alexeenko and Elizabeth M. Topp, in Drying Technologies for Biotechnology and Pharmaceutical Applications: Current Status and Future Trends, Satoshi Ohtake, Ken-Ichi Izutsu and David Lechuga (Eds.), Wiley VCH Verlag GmbH, Weinheim, Germany, 2020, pp. 357-372. ISBN (print): 978-3-527-34112-2.