Engineering high performing LNPs with enhanced stability
- Reference number
- FID24-0014
- Project leader
- Nordström, Randi
- Start and end dates
- 250801-300731
- Amount granted
- 3 250 000 SEK
- Administrative organization
- RISE Research Institutes of Sweden, Stockholm
- Research area
- Life Sciences
Summary
The COVID-19 pandemic changed our view on genetic vaccines. Lipid nanoparticles (LNPs) protect and deliver mRNA in SARS-CoV-2 vaccines. However, they require storage at –80 °C, limiting applications. There's limited data on factors affecting LNP stability. We propose a unique physicochemical approach to identify intermolecular interactions governing stability in hydrated and dry states. Stability and efficacy often conflict for LNPs, a deeper chemical understanding would aid novel LNP development for biological modalities in academia and industry. Expected outcomes are understanding interactions governing LNP stability and function, optimizing design and advancing Life Science in Sweden. This will contribute to smart LNP development for biological drugs and advancements in LSRI utilization in nanotechnology and pharmaceutical sciences. Primary objectives are to identify intermolecular forces that affect LNP stability and function, assess how different conditions and additives impact interactions, and aid in predicting LNP function and shelf-life stability. Methodologies include making systematically varied LNPs using microfluidics and subjecting them to different storage conditions. Both bench-top and LSRI physiochemical methods and in vitro and in vivo evaluation will be used for LNP characterization to couple chemical changes to biological function. The unique combination of physiochemical studies, in vivo function and imaging can revolutionize nucleic acid therapeutics.
Popular science description
With the Covid pandemic, mRNA-LNP vaccines emerged as a groundbreaking technology, offering a quick vaccine development. Formulation developers and regulatory instances collaborated around the clock to get products approved and on the market, to get vaccination programs in motion in order to save as many lives as possible. A critical component of these vaccines is the lipid nanoparticle (LNP) that encapsulates the mRNA and aids its delivery to cells in the body. The LNPs in the Covid vaccines are not stable at room temperature, they require cold (-20 or -78 °C) storage and transportation which makes these products unavailable to economically unfavored parts of the world without developed cold distribution and storage facilities. In addition, the cold storage and short shelf-life leads to disposal of mistreated or expired doses, dramatically increasing the price per administered dose as well as increasing the environmental impact of mRNA-LNP vaccines. A key to making mRNA-LNP vaccines more available worldwide, and to encourage exploration of LNP application in other treatments and therapies is to understand the origin of instability and how this can be controlled and/or avoided. We propose using advanced physiochemical techniques to study a wide range of systematically varied recipes for lipid nanoparticles and through these studies attempt to map origins of instability. This knowledge can then be used to learn how to design and develop more stable LNPs with milder storage conditions. The reduced manufacturing and distribution cost this leads to will in turn contribute to making mRNA-LNP vaccines more available world-wide and to making them economically feasible to explore for other diseases and treatments with lower market value than Covid during the pandemic, and for other administrative routes as e.g. inhalation and topical treatments of biological drugs.