Optimization of Lipid Nanoparticles for Intramuscular Administration of mRNA Vaccines
By Kimberly J. Hassett, K. Benenato, E. Jacquinet, Aisha Lee, Angela Woods, Olga Yuzhakov, S. Himansu, Jessica Deterling, B. Geilich, T. Ketova and 9 more. Molecular Therapy: Nucleic Acids, 2019
754 citations recorded by the source corpus.
mRNA vaccines have the potential to tackle many unmet medical needs that are unable to be addressed with conventional vaccine technologies. A potent and well-tolerated delivery technology is integral to fully realizing the potential of mRNA vaccines. Pre-clinical and clinical studies have demonstrated that mRNA delivered intramuscularly (IM) with first-generation lipid nanoparticles (LNPs) generates robust immune responses. Despite progress made over the past several years, there remains significant opportunity for improvement, as the most advanced LNPs were designed for intravenous (IV) delivery of siRNA to the liver. Here, we screened a panel of proprietary biodegradable ionizable lipids for both expression and immunogenicity in a rodent model when administered IM. A subset of compounds was selected and further evaluated for tolerability, immunogenicity, and expression in rodents and non-human primates (NHPs). A lead formulation was identified that yielded a robust immune response with improved tolerability. More importantly for vaccines, increased innate immune stimulation driven by LNPs does not equate to increased immunogenicity, illustrating that mRNA vaccine tolerability can be improved without affecting potency.
Subfields: Animal Science and Zoology, Immunology, Molecular Biology
View Paper: https://www.semanticscholar.org/paper/6ff3fee927d4aa047ace07a608a8280fa283b0ba
How researchers see this paper
The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.
In Animal Science and Zoology
In Molecular Biology
- J. Kulkarni
- Min Wu
- Camilla Hald Albertsen
- Ralph S. Baric
- K. Petersson
- Marianne Lind
- J. Simonsen
- Sayda M. Elbashir
Citations in the corpus
- SARS-CoV-2 mRNA Vaccine Design Enabled by Prototype Pathogen Preparedness (2020, positive): “The mRNA was encapsulated in a lipid nanoparticle through a modified ethanol-drop nanoprecipitation process as described previously 20 .”
- The role of lipid components in lipid nanoparticles for vaccines and gene therapy (2022, positive): “[23] drew similar conclusions and, using 30 different LNPs in mice, illustrated that mRNA-LNP immunogenicity depended highly on the ionizable lipid structure.”
- mRNA-based therapeutics: powerful and versatile tools to combat diseases (2022, background): “administration, these data indicated that different administration routes would result in different protein expression.(152) In addition, degradable or nondegradable lipoids have been designed and investigated for intravenous or local delivery of mRNA to targeted tissues and cells.”